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  1. The Thoracic Surgery Service at Memorial Sloan Kettering Cancer Center.

    PubMed

    Rusch, Valerie W

    2015-01-01

    The development of the Thoracic Surgery Service at Memorial Sloan Kettering Cancer Center paralleled the emergence of Thoracic Surgery as a specialty, but with the unique focus on oncology and multidisciplinary cancer care characteristic of the institution. From the early post-war years treating lung cancer with new surgical techniques, through early definitive work in malignant mesothelioma, to today's translational research in cancer biology, the Thoracic Surgery Service continues to be an international leader in educating surgeons in thoracic surgical oncology, conducting clinical trials, and developing innovative therapies to treat thoracic cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A Personal Reflection on the History of Radiation Oncology at Memorial Sloan-Kettering Cancer Center

    SciTech Connect

    Chu, Florence C.H.

    2011-07-01

    Purpose: To provide a historical and personal narrative of the development of radiation oncology at Memorial Sloan-Kettering Cancer Center (MSKCC), from its founding more than 100 years ago to the present day. Methods and Materials: Historical sources include the Archives of MSKCC, publications by members of MSKCC, the author's personal records and recollections, and her communications with former colleagues, particularly Dr. Basil Hilaris, Dr. Zvi Fuks, and Dr. Beryl McCormick. Conclusions: The author, who spent 38 years at MSKCC, presents the challenges and triumphs of MSKCC's Radiation Oncology Department and details MSKCC's breakthroughs in radiation oncology. She also describes MSKCC's involvement in the founding of the American Society for Therapeutic Radiology and Oncology.

  3. Integrative cancer care in a US academic cancer centre: The Memorial Sloan-Kettering Experience.

    PubMed

    Deng, G

    2008-08-01

    Various surveys show that interest in complementary and alternative medicine (CAM) is high among cancer patients. Patients want to explore all options that may help their treatment. Many CAM modalities offer patients an active role in their self-care, and the resulting sense of empowerment is very appealing. On the other hand, many unscrupulous marketeers promote alternative cancer "cures," targeting cancer patients who are particularly vulnerable. Some alternative therapies can hurt patients by delaying effective treatment or by causing adverse effects or detrimental interactions with other medications. It is not in the best interest of cancer patients if they cannot get appropriate guidance on the use of CAM from the health care professionals who are part of their cancer care team. The Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center in New York was established in 1999 to address patient interest in cam, to incorporate helpful complementary therapies into each patient's overall treatment management, to guide patients in avoiding harmful alternative therapies, and to develop prospective research to evaluate the efficacy of CAM modalities.

  4. Precision medicine at Memorial Sloan Kettering Cancer Center: clinical next-generation sequencing enabling next-generation targeted therapy trials

    PubMed Central

    Hyman, David M.; Solit, David B.; Arcila, Maria E.; Cheng, Donavan; Sabbatini, Paul; Baselga, Jose; Berger, Michael F.; Ladanyi, Marc

    2016-01-01

    Implementing a center-wide precision medicine strategy at a major cancer center is a true multidisciplinary effort and requires comprehensive alignment of a broad screening strategy with a clinical research enterprise that can use these data to accelerate development of new treatments. Here, we describe the genomic screening approach at Memorial Sloan Kettering Cancer Center, a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology designated MSK-IMPACT, and how it enables and supports a large clinical trial portfolio enriched for multi-histology, biomarker-selected, ‘basket’ studies of targeted therapies. PMID:26320725

  5. Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: The Memorial Sloan-Kettering Cancer Center experience

    SciTech Connect

    Arruda, Fernando F. de; Puri, Dev R.; Zhung, Joanne; Narayana, Ashwatha; Wolden, Suzanne; Hunt, Margie; Stambuk, Hilda; Pfister, David; Kraus, Dennis; Shaha, Ashok; Shah, Jatin; Lee, Nancy Y. . E-mail: leen2@mskcc.org

    2006-02-01

    Purpose: To review the Memorial Sloan-Kettering Cancer Center's experience in using intensity-modulated radiation therapy (IMRT) for the treatment of oropharyngeal cancer. Methods and Materials: Between September 1998 and June 2004, 50 patients with histologically confirmed cancer of the oropharynx underwent IMRT at our institution. There were 40 men and 10 women with a median age of 56 years (range, 28-78 years). The disease was Stage I in 1 patient (2%), Stage II in 3 patients (6%), Stage III in 7 (14%), and Stage IV in 39 (78%). Forty-eight patients (96%) received definitive treatment, and 2 (4%) were treated in the postoperative adjuvant setting. Concurrent chemotherapy was used in 43 patients (86%). Patients were treated using three different IMRT approaches: 76% dose painting, 18% concomitant boost with IMRT in both am and pm deliveries, and 6% concomitant boost with IMRT only in pm delivery. Regardless of the approach, the average prescription dose to the gross tumor planning target volume was 70 Gy, while the average dose delivered to the subclinical volume was 59.4 Gy in the dose painting group and 54 Gy in the concomitant boost group. Percutaneous endoscopic gastrostomy feeding tubes (PEGs) were placed before the beginning of treatment in 84% of the patients. Acute and late toxicity were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Toxicity was also evaluated using subjective criteria such as the presence of esophageal stricture, and the need for PEG usage. The local progression-free, regional progression-free, and distant metastases-free rates, and overall survival were calculated using the Kaplan-Meier method. Results: Three patients had persistent locoregional disease after treatment. The 2-year estimates of local progression-free, regional progression-free, distant metastases-free, and overall survival were 98%, 88%, 84%, and 98%, respectively. The worst acute mucositis experienced was Grade 1

  6. Melanoma and non-melanoma skin cancers in hairy cell leukaemia: a SEER population analysis and the 30-year experience at Memorial Sloan Kettering Cancer Center

    PubMed Central

    Watts, Justin M; Kishtagari, Ashwin; Hsu, Meier; Lacouture, Mario E; Postow, Michael A; Park, Jae H; Stein, Eytan M; Teruya-Feldstein, Julie; Abdel-Wahab, Omar; Devlin, Sean M; Tallman, Martin S

    2016-01-01

    Few studies have examined melanoma and non-melanoma skin cancer (NMSC) incidence rates after a diagnosis of hairy cell leukaemia (HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and Surveillance, Epidemiology and End Results (SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11.3%, melanoma 4.4% and NMSC 6.9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma. Of 4,750 SEER patients with HCL, 55 (1.2%) had a subsequent diagnosis of melanoma. Standardized incidence ratios (SIRs) did not show that melanoma was more common in HCL patients versus the general population (SIR 1.3, 95% CI 0.78–2.03). Analysis of SEER HCL patients diagnosed before and after 1990 (approximately before and after purine analogue therapy was introduced) showed no evidence of an increased incidence after 1990. A better understanding of any potential association between HCL and skin cancer is highly relevant given ongoing trials using BRAF inhibitors, such as vemurafenib, for relapsed HCL, as RAS-mutant skin cancers could be paradoxically activated in these patients. PMID:26115047

  7. Intensity-Modulated Radiotherapy in the Treatment of Oropharyngeal Cancer: An Update of the Memorial Sloan-Kettering Cancer Center Experience

    SciTech Connect

    Setton, Jeremy; Caria, Nicola; Romanyshyn, Jonathan; Koutcher, Lawrence; Wolden, Suzanne L.; Zelefsky, Michael J.; Rowan, Nicholas; Sherman, Eric J.; Fury, Matthew G.; Pfister, David G.; Wong, Richard J.; Shah, Jatin P.; Kraus, Dennis H.; Shi Weiji; Zhang Zhigang; Schupak, Karen D.; Gelblum, Daphna Y.; Rao, Shyam D.; Lee, Nancy Y.

    2012-01-01

    Purpose: To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). Methods and Materials: Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. Results: Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia {>=}Grade 2 was 11% and 29%, respectively. Conclusions: Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.

  8. Efficacy of sorafenib correlates with Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification and bone metastasis in Chinese patients with metastatic renal cell carcinoma.

    PubMed

    Zhang, Yushi; Li, Yongqiang; Cai, Yi; Wang, Ke; Li, Hanzhong

    2016-02-01

    Several prognostic models have been developed to assess the efficacy and safety of sorafenib for metastatic renal cell carcinoma (mRCC), but few studies have validated its use in Chinese patients. The objective of this single center, single arm retrospective study was to examine the efficacy and safety of sorafenib and its related prognostic clinico-pathologic factors in Chinese mRCC patients. One hundred thirty four mRCC patients were enrolled. All patients received 400 mg of sorafenib orally twice daily. The dose was subsequently adjusted in the event of treatment-induced toxicity. Tumor response, progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were determined. The median PFS and OS were 10 months (1-36 months) and 22 months (2-37 months), respectively. Complete, partial, and stable disease were observed in two (1.49%), 24 (17.91%), and 99 (73.88%) patients, respectively. Hand/foot skin reactions, diarrhea and fatigue were the most commonly observed AEs following sorafenib treatment. Among the AEs, only 13 grades 3 and 4 were observed. Multivariate analysis revealed that independent predictive factors for PFS included Eastern Cooperative Oncology Group (ECOG) status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk status, and bone metastasis (all p < 0.05). Factors associated with OS included MSKCC risk values, bone metastasis and sorafenib-induced hypertension (all p < 0.05). The introduction of sorafenib therapy for mRCC in Chinese patients may lead to a favorable disease control with acceptable tolerability. In addition, the parameters predicting favorable outcomes, including ECOG status, MSKCC risk status and bone metastasis, may have prognostic value in clinical practice.

  9. Treatment of Advanced or Recurrent Endometrial Carcinoma with Doxorubicin in Patients Progressing after Paclitaxel/Carboplatin: Memorial Sloan-Kettering Cancer Center (MSKCC) Experience from 1995-2009

    PubMed Central

    Makker, Vicky; Hensley, Martee L.; Zhou, Qin; Iasonos, Alexia; Aghajanian, Carol. A.

    2013-01-01

    Objective Long-term survival for patients with advanced endometrial carcinoma is poor, and limited options exist for the management of recurrent disease. Our goal was to investigate the activity of doxorubicin in the second-line setting in patients who progressed after paclitaxel/carboplatin adjuvant treatment. Methods We conducted a retrospective analysis of patients with recurrent endometrial carcinoma who were treated at Memorial Sloan-Kettering Cancer Center from 1995-2009, and who received paclitaxel/carboplatin adjuvant chemotherapy followed by second-line doxorubicin therapy at time of recurrence. The median PFS and OS times following paclitaxel/carboplatin and following second-line doxorubicin therapy were estimated using the Kaplan-Meier method. Toxicity was assessed by the treating physician at each visit and graded using version 4.0 of Common Terminology Criteria for Adverse Events (CTCAE). Patient presentation, treatment, patterns of recurrence, and patient outcomes were summarized. Results Seventeen patients were included in study analyses. The median PFS from completion of paclitaxel/carboplatin was 8.0 months (95% CI: 4.5-13.6 months). At the time of recurrence, all 17 patients were treated with doxorubicin as second-line therapy. No patient achieved objective response of stable disease. The median PFS of this cohort following doxorubicin treatment was 2.1 months (95% CI: 0.95-2.7) months. Median OS was 5.8 months (95% CI: 1.0-15.0 months). There is only one patient still alive; her median follow-up time is 49.4 months. Predominant doxorubicin-related grade 2 toxicities included nausea/vomiting (18.8%), fatigue (18.8%), and neutropenia (12.5%). No grade 3 or 4 toxicities occurred. Conclusions Among patients with advanced endometrial carcinoma who had received adjuvant paclitaxel/carboplatin, treatment with doxorubicin at time of disease recurrence failed to achieve any objective responses and was associated with a very short (2 months) time to

  10. Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience

    SciTech Connect

    Wolden, Suzanne L. . E-mail: woldens@mskcc.org; Chen, William C.; Pfister, David G.; Kraus, Dennis H.; Berry, Sean L.; Zelefsky, Michael J.

    2006-01-01

    Purpose: We previously demonstrated that intensity-modulated radiation therapy (IMRT) significantly improves radiation dose distribution over three-dimensional planning for nasopharynx cancer and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of patients with longer follow-up. Methods and Materials: Since 1998, all 74 patients with newly diagnosed, nonmetastatic nasopharynx cancer were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost, and more recently 15 received once-daily treatment with dose painting. With the exception of Stage I disease (n = 5) and patient preference (n = 1), 69 patients received concurrent and adjuvant platinum-based chemotherapy similar to that in the Intergroup 0099 trial. Results: Patient characteristics: median age 45; 32% Asian; 72% male; 65% World Health Organization III; 6% Stage I, 16% Stage II, 30% Stage III, 47% Stage IV. Median follow-up is 35 months. The 3-year actuarial rate of local control is 91%, and regional control is 93%; freedom from distant metastases, progression-free survival, and overall survival at 3 years are 78%, 67%, and 83%, respectively. There was 100% local control for Stage T1/T2 disease, compared to 83% for T3/T4 disease (p = 0.01). Six patients failed at the primary site, with median time to local tumor progression 16 months; 5 were exclusively within the 70 Gy volume, and 1 was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for 35 patients treated before 1998 with three-dimensional planning and chemotherapy (p 0.11). Six months posttherapy, 21%, 13%, 15%, and 0% of patients with follow-up audiograms (n = 24 patients) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n = 59), rates of long-term xerostomia were as follows: 26% none

  11. Melanoma and non-melanoma skin cancers in hairy cell leukaemia: a Surveillance, Epidemiology and End Results population analysis and the 30-year experience at Memorial Sloan Kettering Cancer Center.

    PubMed

    Watts, Justin M; Kishtagari, Ashwin; Hsu, Meier; Lacouture, Mario E; Postow, Michael A; Park, Jae H; Stein, Eytan M; Teruya-Feldstein, Julie; Abdel-Wahab, Omar; Devlin, Sean M; Tallman, Martin S

    2015-10-01

    Few studies have examined melanoma and non-melanoma skin cancer (NMSC) incidence rates after a diagnosis of hairy cell leukaemia (HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and Surveillance, Epidemiology and End Results (SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11·3%, melanoma 4·4% and NMSC 6·9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma. Of 4750 SEER patients with HCL, 55 (1·2%) had a subsequent diagnosis of melanoma. Standardized incidence ratios (SIRs) did not show that melanoma was more common in HCL patients versus the general population (SIR 1·3, 95% CI 0·78-2·03). Analysis of SEER HCL patients diagnosed before and after 1990 (approximately before and after purine analogue therapy was introduced) showed no evidence of an increased incidence after 1990. A better understanding of any potential association between HCL and skin cancer is highly relevant given ongoing trials using BRAF inhibitors, such as vemurafenib, for relapsed HCL, as RAS-mutant skin cancers could be paradoxically activated in these patients. © 2015 John Wiley & Sons Ltd.

  12. Randomized controlled trials of the efficacy of lung cancer screening by sputum cytology revisited: a combined mortality analysis from the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study.

    PubMed

    Doria-Rose, V Paul; Marcus, Pamela M; Szabo, Eva; Tockman, Melvyn S; Melamed, Myron R; Prorok, Philip C

    2009-11-01

    : Two randomized controlled trials of lung cancer screening initiated in the 1970s, the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study, compared 1 arm that received annual chest X-ray and 4-monthly sputum cytology (dual-screen) to a second arm that received annual chest X-ray only. Previous publications from these trials reported similar lung cancer mortality between the 2 groups. However, these findings were based on incomplete follow-up, and each trial on its own was underpowered to detect a modest mortality benefit. : The authors estimated the efficacy of lung cancer screening with sputum cytology in an intention-to-screen analysis of lung cancer mortality, using combined data from these trials (n = 20,426). : Over (1/2) of squamous cell lung cancers diagnosed in the dual-screen group were identified by cytology; these cancers tended to be more localized than squamous cancers diagnosed in the X-ray only arm. After 9 years of follow-up, lung cancer mortality was slightly lower in the dual-screen than in the X-ray only arm (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.05). Reductions were seen for squamous cell cancer deaths (RR, 0.79; 95% CI, 0.54-1.14) and in the heaviest smokers (RR, 0.81; 95% CI, 0.67-1.00). There were also fewer deaths from large cell carcinoma in the dual-screen group, although the reason for this is unclear. : These data are suggestive of a modest benefit of sputum cytology screening, although we cannot rule out chance as an explanation for these findings. Cancer 2009. (c) 2009 American Cancer Society.

  13. Randomized controlled trials of the efficacy of lung cancer screening by sputum cytology revisited: a combined mortality analysis from the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study

    PubMed Central

    Doria-Rose, V. Paul; Marcus, Pamela M.; Szabo, Eva; Tockman, Melvyn S.; Melamed, Myron R.; Prorok, Philip C.

    2009-01-01

    Background Two randomized controlled trials of lung cancer screening initiated in the 1970's, the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study, compared one arm which received annual chest x-ray and four-monthly sputum cytology (dual-screen) to a second arm which received annual chest x-ray only. Previous publications from these trials reported similar lung cancer mortality between the two groups. However, these findings were based on incomplete follow-up, and each trial on its own was underpowered to detect a modest mortality benefit. Methods We estimated the efficacy of lung cancer screening with sputum cytology in an intention-to-screen analysis of lung cancer mortality, using combined data from these trials (n=20,426). Results Over one-half of squamous cell lung cancers diagnosed in the dual-screen group were identified by cytology; these cancers tended to be more localized than squamous cancers diagnosed in the x-ray only arm. After nine years of follow-up, lung cancer mortality was slightly lower in the dual-screen than in the x-ray only arm (rate ratio (RR) 0.88, 95% confidence interval (CI) 0.74-1.05). Reductions were seen for squamous cell cancer deaths (RR 0.79, 95% CI 0.54-1.14) and in the heaviest smokers (RR 0.81, 95% CI 0.67-1.00). There were also fewer deaths from large cell carcinoma in the dual-screen group, though the reason for this is unclear. Conclusions These data are suggestive of a modest benefit of sputum cytology screening, though we cannot rule out chance as an explanation for these findings. PMID:19637354

  14. Role of External Beam Radiotherapy in Patients With Advanced or Recurrent Nonanaplastic Thyroid Cancer: Memorial Sloan-Kettering Cancer Center Experience

    SciTech Connect

    Terezakis, Stephanie A. Lee, Kyungmouk S.; Ghossein, Ronald A.; Rivera, Michael; Tuttle, Robert M.; Wolden, Suzanne L.; Zelefsky, Michael J.; Wong, Richard J.; Patel, Snehal G.; Pfister, David G.; Shaha, Ashok R.; Lee, Nancy Y.

    2009-03-01

    Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

  15. Development and assessment of Memorial Sloan Kettering Cancer Center's Surgical Secondary Events grading system.

    PubMed

    Strong, Vivian E; Selby, Luke V; Sovel, Mindy; Disa, Joseph J; Hoskins, William; Dematteo, Ronald; Scardino, Peter; Jaques, David P

    2015-04-01

    Studying surgical secondary events is an evolving effort with no current established system for database design, standard reporting, or definitions. Using the Clavien-Dindo classification as a guide, in 2001 we developed a Surgical Secondary Events database based on grade of event and required intervention to begin prospectively recording and analyzing all surgical secondary events (SSE). Events are prospectively entered into the database by attending surgeons, house staff, and research staff. In 2008 we performed a blinded external audit of 1,498 operations that were randomly selected to examine the quality and reliability of the data. Of 4,284 operations, 1,498 were audited during the third quarter of 2008. Of these operations, 79 % (N = 1,180) did not have a secondary event while 21 % (N = 318) had an identified event; 91 % of operations (1,365) were correctly entered into the SSE database. Also 97 % (129 of 133) of missed secondary events were grades I and II. There were 3 grade III (2 %) and 1 grade IV (1 %) secondary event that were missed. There were no missed grade 5 secondary events. Grade III-IV events are more accurately collected than grade I-II events. Robust and accurate secondary events data can be collected by clinicians and research staff, and these data can safely be used for quality improvement projects and research.

  16. Differential role of Sloan-Kettering Institute (Ski) protein in Nodal and transforming growth factor-beta (TGF-β)-induced Smad signaling in prostate cancer cells.

    PubMed

    Vo, BaoHan T; Cody, Bianca; Cao, Yang; Khan, Shafiq A

    2012-11-01

    Transforming growth factor-beta (TGF-β) signaling pathways contain both tumor suppressor and tumor promoting activities. We have demonstrated that Nodal, another member of the TGF-β superfamily, and its receptors are expressed in prostate cancer cells. Nodal and TGF-β exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1 and DU145 cells, whereas neither had any effect on the proliferation of LNCaP or PC3 cells. Interestingly, Nodal and TGF-β induced migration in PC3 cells, but not in DU145 cells. TGF-β induced predominantly phosphorylation of Smad3, whereas Nodal induced phosphorylation of only Smad2. We also determined the expression and differential role of Ski, a corepressor of Smad2/3, in Nodal and TGF-β signaling in prostate cancer cells. Similar levels of Ski mRNA were found in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cells and prostate cancer tissue samples. Exogenous Nodal and TGF-β had no effects on Ski mRNA levels. On the other hand, TGF-β induced a rapid degradation of Ski protein mediated by the proteasomal pathway, whereas Nodal had no effect on Ski protein. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous Ski reduced proliferation in DU145 cells and enhanced migration of PC3 cells. We conclude that high levels of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad3 signaling, but Ski protein levels do not influence Nodal and Smad2 signaling.

  17. Imaging of Oxidative Stress in Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    Prostate Cancer PRINCIPAL INVESTIGATOR: Brian M. Zeglis CONTRACTING ORGANIZATION: Memorial Sloan-Kettering Cancer Center New York, NY...27September2012-26September2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Imaging of Oxidative Stress in Prostate Cancer 5b. GRANT NUMBER...NUMBER Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10065 9. SPONSORING / MONITORING AGENCY NAME(S

  18. Radical cystectomy with or without prior irradiation in the treatment of bladder cancer.

    PubMed

    Whitmore, W F; Batata, M A; Ghoneim, M A; Grabstald, H; Unal, A

    1977-01-01

    This is a summary presentation on certain aspects of an experience with the use of radical cystectomy with or without prior irradiation in the treatment of selected patients with bladder cancer at the Memorial Sloan-Kettering Cancer Center.

  19. Use of positron emission tomography scan response to guide treatment change for locally advanced gastric cancer: the Memorial Sloan Kettering Cancer Center experience

    PubMed Central

    Won, Elizabeth; Shah, Manish A.; Schöder, Heiko; Strong, Vivian E.; Coit, Daniel G.; Brennan, Murray F.; Kelsen, David P.; Janjigian, Yelena Y.; Tang, Laura H.; Capanu, Marinela; Rizk, Nabil P.; Allen, Peter J.; Bains, Manjit S.

    2016-01-01

    Background Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non-responders. Methods Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m2, cisplatin 60 mg/m2 day 1, and capecitabine 625 mg/m2 bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., ≥35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m2, irinotecan 50 mg/mg2 day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders. Results Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30–85%] in responders compared with 56% in the non-responder group (95% CI, 20–80%, P=0.93). Conclusions The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial. PMID:27563439

  20. NCI's Dr. Barry Kramer on PBS NewsHour | Division of Cancer Prevention

    Cancer.gov

    Talking about New Cancer Definitions to Avoid Unnecessary Treatments. A panel of doctors and scientists proposed a change to the definition of cancer, in hopes of shifting the way we think about and treat the disease. Gwen Ifill discusses the recommendation with Dr. Barnett Kramer of the National Cancer Institute and Dr. Larry Norton of the Memorial Sloan-Kettering Cancer Center... |

  1. $540 million gift boosts cancer research.

    PubMed

    2014-03-01

    Ludwig Cancer Research, based in New York, NY, announced that it will disburse $540 million from the estate of Daniel K. Ludwig equally to Ludwig Centers at Harvard University, Johns Hopkins University, the Massachusetts Institute of Technology, Memorial Sloan-Kettering Cancer Center, Stanford University, and the University of Chicago.

  2. Genetic Factors in Breast Cancer: Center for Interdisciplinary Biobehavioral Research

    DTIC Science & Technology

    2006-10-01

    Hypnosis Intervention, Dr. Guy Montgomery, Associate Professor, Oncological Sciences 12/14/2005 Patient Navigation for CRC Screening with Low Income...Attending Psychologist Psychiatry and Behavioral Sciences Memorial Sloan-Kettering Cancer Center 4/20/2006 "It’s all in your head: The use of MRI in

  3. Radiation therapy for Ewing's sarcoma: Results from Memorial Sloan-Kettering in the modern era

    SciTech Connect

    La, Trang H.; Meyers, Paul A.; Wexler, Leonard H.; Alektiar, Kaled M.; Healey, John H.; Laquaglia, Michael P.; Boland, Patrick J.; Wolden, Suzanne L. . E-mail: woldens@mskcc.org

    2006-02-01

    Purpose: To evaluate the outcomes of patients with Ewing's sarcoma family of tumors (ESFT) treated with modern radiotherapy techniques with MRI along with optimal chemotherapy. Methods and Materials: The records of all 60 patients with ESFT who received radiation to the primary site between 1990 and 2004 were reviewed. All patients received chemotherapy, including vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. Radiation was used as the sole modality for local control in 31 patients and was given either before (n = 3) or after surgical resection (n = 26) in the remainder. All patients had MRI and CT scan-based treatment planning, and 43% received intensity-modulated radiation therapy. Radiation doses ranged from 30 Gy to 60 Gy (median, 51 Gy), and 35% received hyperfractionated radiotherapy. Results: Median age was 16 years (range, 2-40 years). Because of selection bias for radiotherapy, the majority of primary tumors were centrally located (72%): spine (n = 18), pelvis (n = 15), extremities (n 12), chest wall (n = 5), head and neck (n = 5), and other (n = 5). Thirty-eight percent of patients presented with metastatic disease, and 52% of primary tumors were {>=}8 cm. Actuarial 3-year local control was 77%. The presence of metastases at diagnosis was an adverse prognostic factor for local control (84% vs. 61%, p = 0.036). No other predictive factors for local failure were identified. In patients without metastatic disease, 3-year disease-free and overall survival rates were 70% and 86%, respectively, whereas in patients with metastases they were both 21%. Follow-up of surviving patients was 6-178 months (median, 41 months). Conclusion: In this unfavorable cohort of ESFT patients, radiation therapy was an effective modality for local control, especially for patients without metastases. The presence of metastases at diagnosis is a predictive factor not only for death but also for local failure.

  4. Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center.

    PubMed

    Horvat, Troy Z; Adel, Nelly G; Dang, Thu-Oanh; Momtaz, Parisa; Postow, Michael A; Callahan, Margaret K; Carvajal, Richard D; Dickson, Mark A; D'Angelo, Sandra P; Woo, Kaitlin M; Panageas, Katherine S; Wolchok, Jedd D; Chapman, Paul B

    2015-10-01

    Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival. Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticosteroid treatment for an irAE; 29 (10%) also required anti-TNFα therapy. Defining TTF as either starting a new treatment or death, estimated median TTF was 5.7 months. Twelve percent of patients experienced long-term disease control without receiving additional antimelanoma therapy. OS and TTF were not affected by the occurrence of irAEs or the need for systemic corticosteroids. IrAEs are common in patients treated with ipilimumab. In our experience, approximately one-third of ipilimumab-treated patients required systemic corticosteroids, and almost one-third of those required further immune suppression with anti-TNFα therapy. Practitioners and patients should be prepared to treat irAEs and should understand that such treatment does not affect OS or TTF. © 2015 by American Society of Clinical Oncology.

  5. Preoperative irradiation and cystectomy for bladder cancer.

    PubMed

    Smith, J A; Batata, M; Grabstald, H; Sogani, P C; Herr, H; Whitmore, W F

    1982-03-01

    Between 1971 and 1974, 101 patients at Memorial Sloan-Kettering Cancer Center underwent planned integrated treatment for bladder cancer with 2000 rads by megavoltage delivered to the whole pelvis over five consecutive days followed by radical cystectomy within a week. The overall five-year survival rate was 39%; the hospital mortality rate was 2%. In the pelvis alone tumor recurred in 9% of the patients. These results support other studies demonstrating the efficacy of this and other regimens of preoperative irradiation and cystectomy.

  6. Report From the Jerusalem Workshop on Lynch Syndrome-Hereditary Nonpolyposis Colorectal Cancer

    PubMed Central

    Boland, C. Richard; Shike, Moshe

    2011-01-01

    A Workshop was held in Jerusalem, Israel, on October 26 and 27, 2009 to discuss the management of Lynch syndrome-hereditary nonpolyposis colorectal cancer (CRC), with the primary goal to develop consensus for the optimal management of this disease. A second goal was to identify areas of research with the potential to advance the clinical management of Lynch syndrome. The perspectives and recommendations from the workshop are meant to be a platform for discussion and deliberation. The Workshop was organized by Moshe Shike (Memorial Sloan Kettering Cancer Center, New York) and sponsored by The Colon Cancer Foundation. More details of each presentation are available in an on-line supplement. PMID:20416305

  7. A communication tool for cancer patients with pain: the art therapy technique of the body outline.

    PubMed

    Luzzatto, Paola; Sereno, Valerie; Capps, Roy

    2003-06-01

    The multidimensional aspect of pain suggests the use of multimodal interventions. The Memorial Sloan-Kettering Cancer Center has recently utilized the art therapy modality to help patients communicate the painful side of their illness in such a way that they can feel understood and respected. In this paper we describe a simple innovative art therapy intervention that we have developed within the Art Therapy Service in the Psychiatric Department of Memorial Sloan-Kettering Cancer Center. The patients work with a Body Outline as a starting template, together with the art therapist, in sessions lasting approximately 45 minutes. They are encouraged to fill the space inside and outside the Body Outline. They can use colored pastels, markers, or watercolor or cut out images for a collage. Seventy hospitalized adult cancer patients, 60 women and 10 men, used this intervention between January 1999 and May 2000. We have analyzed the variety of responses from the 70 patients, and three main groups have emerged, which have focused on the following issues: (1) visualization of physical pain, (2) communication of emotions, and (3) search for meaning/spirituality. The results suggest that because of its abstract symbolic feature, the Body Outline is a very flexible therapeutic intervention. It must be offered within the relationship with the art therapist, and it may fulfill quite a variety of expressive needs, from the description of physical pain to the elaboration of spiritual longings.

  8. Functional results after radiochemotherapy and total mesorectal excision for rectal cancer.

    PubMed

    Coco, C; Valentini, V; Manno, A; Rizzo, G; Gambacorta, M A; Mattana, C; Verbo, A; Picciocchi, A

    2007-08-01

    The aim of this study was to prospectively define and measure evacuation and continence disorders after preoperative radiochemotherapy and total mesorectal excision (TME) for rectal cancer 1 year after surgery. We submitted 100 patients, who underwent neoadjuvant treatment and anterior resection with TME from 1996 to 2003, to a questionnaire on postoperative continence and evacuation. Anal sphincter function was further assessed by the Memorial Sloan-Kettering score. Factors influencing anorectal function were examined in univariate and multivariate analysis. Median evacuation score was 16.12 +/- 5.12 (range 0-28). Sensation of incomplete evacuation was reported in 58% of cases, necessity to return to the bathroom <15 min in 37% and inability to evacuate completely <15 min in 35%. Median continence score was 13.7 +/- 4.79 (range 0-20). Incontinence to flatus was reported in 46% of cases. Colonic J-pouch allows better evacuation and continence. Continence was also better in absence of postoperative complications. Sphincter function resulted excellent or good in 75% of patients according to the Memorial Sloan-Kettering score. The most frequent symptoms in our series are the sensation of incomplete evacuation, the incontinence to flatus, and the necessity to return to the bathroom <15 min. Colonic J-pouch warrants a better function. Postoperative complications compromise good functional results.

  9. [Means and methods of alternative therapy for cancer: acupuncture--the effects and mechanisms of action].

    PubMed

    Korman, D B

    2014-01-01

    Among means of alternative and complementary therapy for cancer, acupuncture holds a special place. This is because, unlike the most other methods of alternative and complementary therapy for cancer, efficacy and safety of acupuncture in the symptomatic treatment for cancer patients is considered as proven. Not accidentally such leading cancer centers in the USA as the Dana-Farber Cancer Institute in Boston, the Memorial Sloan-Kettering Cancer Center in New York, the M.D.Anderson Cancer Center in Houston integrated acupuncture in accepted in these centers treatment standards and are staffed by licensed professionals on acupuncture. Particular attention is drawn to the use of acupuncture in hospices. It is stressed that it is the most effective and safe in the performance by qualified licensed professionals

  10. Back to the Future: Are Tumor-Targeting Bacteria the Next-Generation Cancer Therapy?

    PubMed

    Hoffman, Robert M

    2015-01-01

    Cancer patients infected with various bacteria were reported, for at least two centuries, to have spontaneous remission. W.B. Coley, of what is now the Memorial Sloan-Kettering Cancer Center, pioneered bacterial therapy of cancer in the clinic with considerable success beginning in the late nineteenth century. After Coley died in 1936, bacterial therapy of cancer essentially ended. Currently there is much excitement in developing bacterial therapy for treating cancer using either obligate or facultative anaerobic bacteria. This chapter will demonstrate the potential and strategy of Salmonella typhimurium A1-R, an engineered tumor-targeting variant for the systemic treatment of metastatic cancer. A new concept using Salmonella typhimurium A1-R for cell cycle "decoy" chemotherapy of metastatic cancer is also described.

  11. Future of Bacterial Therapy of Cancer.

    PubMed

    Hoffman, Robert M

    2016-01-01

    Bacterial therapy of cancer has a centuries-long history and was first-line therapy at the hospital in New York City that would become Memorial Sloan-Kettering Cancer Center, under Dr. William B. Coley. However, after Coley's death in 1936, bacterial therapy of cancer ceased in the clinic until the present century. Clinical trials have been recently carried out for strains of the obligate anaerobe Clostridium novyi with the toxin gene deleted, and on an attenuated strain of Salmonella typhimurium (S. typhimurium), which is a facultative anaerobe that can grow in viable, as well as necrotic, areas of tumors, unlike Clostridium, which can only grow in the hypoxic areas. Our laboratory has developed the novel strain S. typhimurium A1-R that is effective against all tumor types in clinically-relevant mouse models, including patient-derived orthotopic xenograft (PDOX) mouse models. This chapter suggests future clinical applications for S. typhimurium A1-R.

  12. Exploring cell apoptosis and senescence to understand and treat cancer: an interview with Scott Lowe.

    PubMed

    Lowe, Scott; Cifra, Alessandra

    2015-11-01

    Scott W. Lowe is currently principal investigator at the Memorial Sloan-Kettering Cancer Center. After beginning his studies in chemical engineering, he decided to take another path and became fascinated by biochemistry, genetics and molecular biology, which ultimately led to an interest in human disease, particularly cancer. During his PhD at the Massachusetts Institute of Technology (MIT), Scott had the opportunity to benefit from the exceptional mentorship of Earl Ruley, David Housman and Tyler Jacks, and contributed to elucidating how the p53 (TP53) tumor suppressor gene limits oncogenic transformation and modulates the cytotoxic response to conventional chemotherapy. This important work earned him a fellowship from the Cold Spring Harbor Laboratory, which helped to launch his independent career. Scott is now a leading scientist in the cancer field and his work has helped to shed light on mechanisms of cell apoptosis and senescence to better understand and treat cancer. In this interview, he talks about this incredible scientific journey.

  13. Commentary on: "Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): A multicentre, randomised, double-blind, phase 3 trial." Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengeløv L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR, CA184-043 Investigators. Departments of Urology and Immunology and Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA, Electronic address: kwon.eugene@mayo.edu; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Brady Urological Institute, Baltimore, MD, USA; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA; Institut Gustave Roussy, University of Paris-Sud, Villejuif, France; Institut Gustave Roussy, Villejuif, France; VU University Medical Centre, Amsterdam, Netherlands; Vienna General Hospital, Medical University Vienna, Vienna, Austria; Institut Bergonié, Bordeaux, France; CHU Caremeau, Nimes, France; Centro Médico Austral, Buenos Aires, Argentina; Centre Jean Perrin, Clermont-Ferrand, France; St John of God Hospital, Subiaco, WA, Australia; University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy; Hospital de Caridade de Ijuí, Ijuí, Brazil; Nottingham University Hospital, Nottingham, UK; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Netherlands Cancer Institute and Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; Institute of Oncology Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania; Hospital Británico de Buenos Aires, Buenos Aires, Argentina; Herlev Hospital, Herlev, Denmark; Odense University Hospital, Odense, Denmark; University of Texas MD Anderson Cancer Center, Houston,

    PubMed

    Trump, Donald

    2016-05-01

    Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel chemotherapy. We did a multicentre, randomised, double-blind, phase 3 trial in which men with at least one bone metastasis from castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned in a 1:1 ratio to receive bone-directed radiotherapy (8Gy in one fraction) followed by either ipilimumab 10mg/kg or placebo every 3 weeks for up to four doses. Non-progressing patients could continue to receive ipilimumab at 10mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly assigned to either treatment group via a minimisation algorithm, and stratified by Eastern Cooperative Oncology Group performance status, alkaline phosphatase concentration, haemoglobin concentration, and investigator site. Patients and investigators were masked to treatment allocation. The primary endpoint was overall survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00861614. From May 26, 2009, to Feb 15, 2012, 799 patients were randomly assigned (399 to ipilimumab and 400 to placebo), all of whom were included in the intention-to-treat analysis. Median overall survival was 11.2 months (95% CI: 9.5-12.7) with ipilimumab and 10.0 months (8.3-11.0) with placebo (hazard ratio [HR] = 0.85, 0.72-1.00; P = 0.053). However, the assessment of the proportional hazards assumption showed that it was violated (P = 0.0031). A piecewise hazard model showed that the HR changed over time: the HR for 0-5 months was 1.46 (95% CI: 1.10-1.95), for 5-12 months was 0.65 (0.50-0.85), and beyond 12 months was 0.60 (0.43-0.86). The most common grade 3

  14. Factors of prognostic and therapeutic significance in patients with bladder cancer. [X ray

    SciTech Connect

    Batata, M.A.; Chu, F.C.H.; Hilaris, B.S.; Kim, Y.S.; Lee, M.Z.; Chung, S.; Whitmore, W.F.

    1981-05-01

    In a two-decade period, 451 patients with bladder cancer were treated by external megavoltage irradiation and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was performed in 137 patients. One-hundred nine patients underwent radical cystectomy for cancer recurrence or persistence +- 1 year after radical irradiation averaging 6000 rad tumor dose in 6 weeks. Planned preoperative pelvic irradiation either 4000 rad in 4 weeks in 119 patients or 2000 rad in 1 week in 86 patients was followed by radical cystectomy after average intervals of 6 weeks and 2 days, respectively. Similarly more favorable 5-year survival results were observed with prior radical or preoperative conventional or shorter regimen irradiation than with cystectomy alone. The main pelvic complications from this treatment are discussed.

  15. The handling of antineoplastic drugs in a major cancer center.

    PubMed

    Hoffman, D M

    1980-06-01

    It has long been known that many commonly used antineoplastic agents are carcinogenic. Yet most health care professionals take few precautions, if any, when handling these drugs. Recent findings suggest a possible hazard to personnel as evidenced by increased mutagenicity of urine of nurses exposed to anticancer drugs during preparation and administration of doses. Although more study is needed to determine the significance of these data, it would seem prudent to take measures to prevent any unnecessary exposure to these drugs by those preparing and administering them. The policies and procedures at the Memorial Sloan-Kettering Cancer Center require that chemotherapeutic drugs be prepared in a vertical laminar flow containment hood by personnel wearing sterile disposable gloves. Chemotherapeutic agents are specially labeled to ensure segregated disposal of waste, which is subsequently incinerated.

  16. EDI and imaging automate the business office.

    PubMed

    McBride, J S; Moynihan, J J

    1999-01-01

    By implementing electronic remittance posting and imaging in patient accounting, New York's Memorial Sloan-Kettering Cancer Center was able to eliminate 22 full-time equivalent supervisory and staff positions and save $365,000 in physical space, microfilm and media costs the first year the new system was operational. Memorial Sloan-Kettering currently is participating in a pilot program with its Medicare fiscal intermediary to determine how EDI can be used to manage claim-status information between payer and provider. By combining EDI, fax, and imaging technologies, Memorial Sloan-Kettering is making its patient accounting process more efficient and providing better service to its patients.

  17. Putting TCGA Data to Work - TCGA

    Cancer.gov

    Neurosurgeon Cameron Brennan of Memorial Sloan-Kettering Cancer Center used TCGA data to define subgroups of patients with a deadly brain cancer called glioblastoma multiforme. Learn more about his research in this TCGA in Action case study.

  18. Targeting ESR1-Mutant Breast Cancer

    DTIC Science & Technology

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1-Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...ORGANIZATION: Sloan Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: September 2015 TYPE OF REPORT: Annual Technical Report...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1-Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT

  19. Identifying Androgen Receptor-Independent Mechanisms of Prostate Cancer Resistance to Second-Generation Antiandrogen Therapy

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-15-1-0276 TITLE: Identifying Androgen Receptor-Independent Mechanisms of Prostate Cancer Resistance to Second-Generation...Antiandrogen Therapy PRINCIPAL INVESTIGATOR: David Wise, MD, PhD CONTRACTING ORGANIZATION: Sloan Kettering Institute for Cancer Research New York...of Prostate Cancer Resistance to Second-Generation Antiandrogen Therapy 5b. GRANT NUMBER W81XWH-15-1-0276 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  20. ERF is a Potential ERK Modulated Tumor Suppressor in Prostate Cancer

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0277 TITLE: ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rohit...Bose CONTRACTING ORGANIZATION: Sloan Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: October 2016 TYPE OF REPORT...4. TITLE AND SUBTITLE ERF is a Potential ERK-Modulated Tumor Suppressor in Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0277

  1. Clinical and genetic determinants of ovarian metastases from colorectal cancer.

    PubMed

    Ganesh, Karuna; Shah, Ronak H; Vakiani, Efsevia; Nash, Garrett M; Skottowe, Hugh P; Yaeger, Rona; Cercek, Andrea; Lincoln, Anne; Tran, Christina; Segal, Neil H; Reidy, Diane L; Varghese, Anna; Epstein, Andrew S; Sonoda, Yukio; Chi, Dennis; Guillem, Jose; Temple, Larissa; Paty, Philip; Hechtman, Jaclyn; Shia, Jinru; Weiser, Martin; Aguilar, Julio Garcia; Kemeny, Nancy; Berger, Michael F; Saltz, Leonard; Stadler, Zsofia K

    2017-04-01

    Ovarian metastases from colorectal cancer (OM-CRC) often are unresponsive to chemotherapy and are associated with poor survival. To the authors' knowledge, the clinicopathologic and genomic predictors of OM-CRC are poorly characterized and optimal clinical management remains unclear. Women with a histopathological diagnosis of OM-CRC who were treated at Memorial Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next-generation somatic mutation profiling (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]) was performed on 38 OM-CRC cases, including 21 matched tumor pairs/trios. Regression models were used to analyze variables associated with progression-free survival and overall survival (OS). Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations were more frequent in cases of OM-CRC than in instances of CRC occurring without OM. SMAD4 and lysine methyltransferase 2D (KMT2D) mutations were associated with reduced OS. Matched multisite tumor sequencing did not identify OM-specific genomic alterations. Of the 195 patients who underwent oophorectomy for OM-CRC (median age, 49 years with a progression-free survival of 9.4 months and an OS of 23 months from oophorectomy), 76% had extraovarian metastasis (EOM). In multivariable analysis, residual disease after surgery (R2 resection) was associated with worse survival. Patients with EOM were less likely to achieve R0/R1 surgical resection status (complete macroscopic resection without clinical/radiological evidence of disease) (48% vs 94%). However, if R0/R1 resection status was achieved, both patients with (35.9 months vs 12 months) and without (43.2 months vs 14.5 months) EOM were found to have better OS. Among 114 patients with R0/R1 resection status, 23 (20%) had no disease recurrence, including 10 patients (9%) with > 3 years of follow-up. Loss

  2. Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

    PubMed

    Morris, Michael J; Basch, Ethan M; Wilding, George; Hussain, Maha; Carducci, Michael A; Higano, Celestia; Kantoff, Philip; Oh, William K; Small, Eric J; George, Daniel; Mathew, Paul; Beer, Tomasz M; Slovin, Susan F; Ryan, Charles; Logothetis, Christopher; Scher, Howard I

    2009-01-01

    In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

  3. hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR.

    PubMed

    Xu, Bin; Tao, Tao; Wang, Yiduo; Fang, Fang; Huang, Yeqing; Chen, Shuqiu; Zhu, Weidong; Chen, Ming

    2016-10-01

    Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.

  4. Molecular classification of prostate cancer using curated expression signatures.

    PubMed

    Markert, Elke K; Mizuno, Hideaki; Vazquez, Alexei; Levine, Arnold J

    2011-12-27

    High Gleason score is currently the best prognostic indicator for poor prognosis in prostate cancer. However, a significant number of patients with low Gleason scores develop aggressive disease as well. In an effort to understand molecular signatures associated with poor outcome in prostate cancer, we analyzed a microarray dataset characterizing 281 prostate cancers from a Swedish watchful-waiting cohort. Patients were classified on the basis of their mRNA microarray signature profiles indicating embryonic stem cell expression patterns (stemness), inactivation of the tumor suppressors p53 and PTEN, activation of several oncogenic pathways, and the TMPRSS2-ERG fusion. Unsupervised clustering identified a subset of tumors manifesting stem-like signatures together with p53 and PTEN inactivation, which had very poor survival outcome, a second group with intermediate survival outcome, characterized by the TMPRSS2-ERG fusion, and three groups with benign outcome. The stratification was validated on a second independent dataset of 150 tumor and metastatic samples from a clinical cohort at Memorial Sloan-Kettering Cancer Center. This classification is independent of Gleason score and therefore provides useful unique molecular profiles for prostate cancer prognosis, helping to predict poor outcome in patients with low or average Gleason scores.

  5. Assessment of an existing and modified model for predicting non sentinel lymph node metastasis in breast cancer patients with positive sentinel node biopsy.

    PubMed

    Al-Masri, M; Darwazeh, G; El-Ghanem, M; Hamdan, B; Sughayer, M

    2013-01-01

    The Memorial Sloan Kettering Cancer Center (MSKCC) breast nomogram has been validated in different populations. In this study, the nomogram was validated for the first time in a Middle East population sample. Although our sample was found to have significant differences from the dataset from which the model was derived, the nomogram proved to be accurate in predicting non sentinel axillary lymph node metastasis. An attempt to use the proportions of involved sentinel lymph nodes instead of absolute numbers of positive and negative sentinel lymph nodes, yet using the same online calculator to predict the probability of non sentinel axillary lymph node metastasis, improved the accuracy, specificity, negative predictive value, and false negative rate. Axillary clearance is the standard of care in patients with invasive breast cancer and positive sentinel lymph node biopsy. However, in 40-60% of patients, the sentinel lymph nodes are the only involved lymph nodes in the axilla. The Memorial Sloan Kettering Cancer Center (MSKCC) breast nomogram serves to identify a subgroup of patients with low risk of non sentinel lymph node (NSLN) metastasis, in whom axillary lymph node dissection (ALND) could be spared, and thereby, preventing the unwarranted associated morbidity. The MSKCC nomogram was applied on 91 patients who met the criteria. A modified predictive model was developed by substituting proportions of positive and negative SLN for their absolute numbers. The accuracy was assessed by calculating the area under the receiver-operator characteristic (ROC) curve. The MSKCC nomogram achieved an area under the ROC curve of 0.76. The area under the curve for the modified predictive model was 0.81. The specificity, negative predictive value, and false negative were 30%, 71%, 20% (MSKCC model) and 55%, 84%, 17% (modified model) at 20% predicted probability cut-off values. Although differences existed in characteristics of our breast cancer population, and in the methods of

  6. Meeting Report From the Prostate Cancer Foundation Scientific Working Group on Radium-223.

    PubMed

    Miyahira, Andrea K; Morris, Michael; Soule, Howard R

    2017-02-01

    The Prostate Cancer Foundation (PCF) convened a Scientific Working Group Meeting on Radium-223 on September 8, 2016, at The Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center. The meeting was attended by 18 investigators with expertise in radium-223, bone biology, molecular imaging, biomarkers, and prostate cancer clinical trials. The goal of this meeting was to discuss the known and unknown surroundings the therapeutic effects of the bone targeting agent radium-223, in bone metastatic prostate cancer therapy, and to outline the most critical studies needed to improve the clinical use of this agent. Three major topic areas were discussed: (1) the basic science of radium; (2) immuno-adjuvant properties of radium therapy; and (3) high impact clinical trials and correlative science. This article reviews the major topics discussed at the meeting for the purpose of accelerating studies that will improve the use of radium-223 in the treatment of prostate cancer patients. Prostate 77:245-254, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Spectrum of nonconvulsive status epilepticus in patients with cancer.

    PubMed

    Spindler, Meredith; Jacks, Lindsay M; Chen, Xi; Panageas, Katherine; DeAngelis, Lisa M; Avila, Edward K

    2013-08-01

    Determine incidence, clinical presentation, electrographic correlates, and outcome of nonconvulsive status epilepticus (NCSE) in cancer patients on whom an EEG was performed. Retrospective review of 947 EEG reports on 658 patients in whom any type of EEG was performed at Memorial Sloan-Kettering Cancer Center (July 2006 to March 2008). Using the Epilepsy Research Foundation criteria, patients were classified as definite or probable NCSE. Medical records were reviewed for diagnosis, causes of NCSE, response to treatment, and outcome. Mortality was determined for patients with NCSE. Twenty-six episodes of NCSE were identified in 25 patients (25/658, 4%). Eleven patients had primary brain tumor, 12 patients systemic cancer, and two had both. At diagnostic EEG, 18 were awake, 3 were lethargic, and 5 patients were comatose. EEG revealed a seizure in 62% of the patients, periodic lateralized epileptiform discharges in 42%, and periodic epileptiform discharges in 7.7%. Neuroimaging revealed new intracranial pathology in 54% of the patients. Seventy-seven percent of the patients achieved control; 65% required ≥3 antiepileptic drugs, and 33% required intubation. Three patients died from NCSE. In our cohort, awake NCSE was more common than comatose NCSE. Treatment was successful in patients with heterogeneous central nervous system disease. EEG evaluation should be considered in patients with cancer because NCSE is treatable despite a high prevalence of structural brain disease. Nonconvulsive status epilepticus control did not always require intubation and burst suppression, but frequently required three or more antiepileptic drugs.

  8. Comprehensive detection of germline variants by MSK-IMPACT, a clinical diagnostic platform for solid tumor molecular oncology and concurrent cancer predisposition testing.

    PubMed

    Cheng, Donavan T; Prasad, Meera; Chekaluk, Yvonne; Benayed, Ryma; Sadowska, Justyna; Zehir, Ahmet; Syed, Aijazuddin; Wang, Yan Elsa; Somar, Joshua; Li, Yirong; Yelskaya, Zarina; Wong, Donna; Robson, Mark E; Offit, Kenneth; Berger, Michael F; Nafa, Khedoudja; Ladanyi, Marc; Zhang, Liying

    2017-05-19

    The growing number of Next Generation Sequencing (NGS) tests is transforming the routine clinical diagnosis of hereditary cancers. Identifying whether a cancer is the result of an underlying disease-causing mutation in a cancer predisposition gene is not only diagnostic for a cancer predisposition syndrome, but also has significant clinical implications in the clinical management of patients and their families. Here, we evaluated the performance of MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) in detecting genetic alterations in 76 genes implicated in cancer predisposition syndromes. Output from hybridization-based capture was sequenced on an Illumina HiSeq 2500. A custom analysis pipeline was used to detect single nucleotide variants (SNVs), small insertions/deletions (indels) and copy number variants (CNVs). MSK-IMPACT detected all germline variants in a set of 233 unique patient DNA samples, previously confirmed by previous single gene testing. Reproducibility of variant calls was demonstrated using inter- and intra- run replicates. Moreover, in 16 samples, we identified additional pathogenic mutations other than those previously identified through a traditional gene-by-gene approach, including founder mutations in BRCA1, BRCA2, CHEK2 and APC, and truncating mutations in TP53, TSC2, ATM and VHL. This study highlights the importance of the NGS-based gene panel testing approach in comprehensively identifying germline variants contributing to cancer predisposition and simultaneous detection of somatic and germline alterations.

  9. Radiation therapy before cystectomy in the management of patients with bladder cancer.

    PubMed

    Batata, M A; Chu, F C; Hilaris, B S; Kim, Y; Lee, M; Chang, B; Whitmore, W F

    1982-01-01

    During the preceding two decades, 309 patients with bladder cancer were treated by irradiation before cystectomy at the Memorial Sloan-Kettering Cancer Center. A radical tumour dose averaging 6000 cGy (rad) in six weeks was given to 104 patients who underwent radical cystectomy +/- one year later for persistent or recurrent cancer. Pre-operative pelvic irradiation was planned in 205 patients who received either 4000 cGy in four weeks (119) or 2000 cGy in one week (86) and underwent radical cystectomy after +/- six weeks and two days, respectively. The determinate five-year survival rates (41-43%) were similar with the three irradiation regimes; mortality under five years was mainly due to cancer recurrence locally and/or distally. Incidence of recurrence with radiation-induced stage reduction (21%) was lower, especially within the pelvis, than with no stage reduction (51%). Treatment results with planned pre-operative irradiation, especially in high stage tumours, were more favourable with the shorter 2000 cGy regimen of high fractional doses than with the conventionally fractionated 4000 cGy regimen.

  10. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    SciTech Connect

    Dikken, Johan L.; Coit, Daniel G.; Baser, Raymond E.; Gönen, Mithat; Goodman, Karyn A.; Brennan, Murray F.; Jansen, Edwin P.M.; Boot, Henk; Velde, Cornelis J.H. van de; Cats, Annemieke; Verheij, Marcel

    2014-03-01

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

  11. Electronic patient self-assessment and management (SAM): a novel framework for cancer survivorship.

    PubMed

    Vickers, Andrew J; Salz, Talya; Basch, Ethan; Cooperberg, Matthew R; Carroll, Peter R; Tighe, Foss; Eastham, James; Rosen, Raymond C

    2010-06-17

    We propose a novel framework for management of cancer survivorship: electronic patient Self-Assessment and Management (SAM). SAM is a framework for transfer of information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice. Patients who participate in the SAM system are contacted by email at regular intervals and asked to complete validated questionnaires online. Patient responses on these questionnaires are then analyzed in order to provide patients with real-time, online information about their progress and to provide them with tailored and standardized medical advice. Patient-level data from the questionnaires are ported in real time to the patient's health care provider to be uploaded to clinic notes. An initial version of SAM has been developed at Memorial Sloan-Kettering Cancer Center (MSKCC) and the University of California, San Francisco (UCSF) for aiding the clinical management of patients after surgery for prostate cancer. Pilot testing at MSKCC and UCSF suggests that implementation of SAM systems are feasible, with no major problems with compliance (> 70% response rate) or security. SAM is a conceptually simple framework for passing information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice.

  12. Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy.

    PubMed

    Estilo, Cherry L; Van Poznak, Catherine H; Wiliams, Tijaana; Bohle, George C; Lwin, Phyu T; Zhou, Qin; Riedel, Elyn R; Carlson, Diane L; Schoder, Heiko; Farooki, Azeez; Fornier, Monica; Halpern, Jerry L; Tunick, Steven J; Huryn, Joseph M

    2008-08-01

    Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past 5 years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate (IVBP) therapy, but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. To further categorize risk factors associated with ONJ and potential clinical outcomes of this condition, we performed a retrospective study of patients with metastatic bone disease treated with intravenous bisphosphonates who have been evaluated by the Memorial Sloan-Kettering Cancer Center Dental Service between January 1, 1996 and January 31, 2006. We identified 310 patients who met these criteria. Twenty-eight patients were identified as having ONJ at presentation to the Dental Service and an additional 7 patients were subsequently diagnosed with ONJ. Statistically significant factors associated with increased likelihood of ONJ included type of cancer, duration of bisphosphonate therapy, sequential IVBP treatment with pamidronate followed by zoledronic acid, comorbid osteoarthritis or rheumatoid arthritis, and benign hematologic conditions. Our data do not support corticosteroid use or oral health as a predictor of risk for ONJ. Clinical outcomes of patients with ONJ were variable with 11 patients demonstrating improvement or healing with conservative management. Our ONJ experience is presented here.

  13. Contralateral Breast Cancers: Independent Cancers or Metastases?

    PubMed

    Begg, Colin B; Ostrovnaya, Irina; Geyer, Felipe C; Papanastasiou, Anastasios D; Ng, Charlotte Ky; Sakr, Rita; Bernstein, Jonine L; Burke, Kathleen A; King, Tari A; Piscuoglio, Salvatore; Mauguen, Audrey; Orlow, Irene; Weigelt, Britta; Seshan, Venkatraman E; Morrow, Monica; Reis-Filho, Jorge S

    2017-09-16

    A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995-2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center. We report results from 49 patients successfully analyzed by a targeted massively parallel sequencing assay. Somatic mutations and copy number alterations were defined by state-of-the-art algorithms. Clonal relatedness was evaluated by statistical tests specifically designed for this purpose. We found evidence that the tumors in contralateral breasts were clonally related in 3 cases (6%) on the basis of matching mutations at codons where somatic mutations are rare. Clinical data and the presence of similar patterns of gene copy number alterations were consistent with metastasis for all 3 cases. In 3 additional cases there was a solitary matching mutation at a common PIK3CA locus. The results suggest that a subset of contralateral breast cancers represent metastases rather than independent primary tumors. Massively parallel sequencing analysis can provide important evidence to clarify the diagnosis. However, given the inter-tumor mutational heterogeneity in breast cancer, sufficiently large gene panels need to be employed to define clonality convincingly in all cases. This article is protected by copyright. All rights reserved. © 2017 UICC.

  14. Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer. Long-term results

    PubMed Central

    Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana García; Payá, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, María; Vázquez, Andrés; Pacheco, Maite; Sanchez, Jesica

    2016-01-01

    ABSTRACT Objectives We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the “Phoenix consensus”. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. PMID:27136466

  15. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  16. An innovative off-campus infusion suite designed to improve experiences of patients with cancer.

    PubMed

    Gordon, Jeanine; Gruber, Marcia

    2012-08-01

    The Brooklyn Infusion Center of Memorial Sloan-Kettering Cancer Center was established in 2010 to better meet the needs of patients with cancer living in the Brooklyn neighborhood and surrounding areas. A multidisciplinary team comprising clinical, administrative, planning, and other representatives were charged to identify and develop a location that would provide oncology care for patients closer to home and improve the patients' experience. The primary objectives were to provide patient-centered care that accommodates the patients' preference to receive treatment closer to home and to take advantage of technology to establish processes that will provide safe, efficient, convenient, and high-quality care in a cost-effective manner. To achieve these objectives, no laboratory processing or pharmacy services were included in the plan for the Brooklyn location. This allowed the elimination of most of the challenges involved with same-day blood draws and chemotherapy orders. In addition, computer technology is used for teledermatology and other medical visits to maintain the continuity of the patients' care with their multidisciplinary teams at the Manhattan, NY, location. The data presented will illustrate how these processes have improved patients' experiences by reducing wait times for treatment, providing treatment closer to home, and implementing a truly patient-centered nursing care model.

  17. Treatment outcomes and secondary cancer incidence in young patients with hairy cell leukaemia.

    PubMed

    Getta, Bartlomiej M; Woo, Kaitlin M; Devlin, Sean; Park, Jae H; Abdel-Wahab, Omar; Saven, Alan; Rai, Kanti; Tallman, Martin S

    2016-11-01

    Repeated therapy of hairy cell leukaemia (HCL) with treatments that have potential long-term toxicities has raised concerns regarding increased risk for younger patients. We compared clinical outcomes and disease complications in 63 patients with HCL aged ≤40 years at diagnosis with 268 patients >40 years treated at Memorial Sloan Kettering Cancer Center. The rate of complete remission following initial therapy was 87% and 83% (P = 0·71) and estimated 10-year overall survival was 100% and 82% (P = 0·25) in younger and older patients, respectively. Younger patients required therapy earlier and had a significantly shorter time between first and second therapy (median: 63 months vs. 145 months) (P = 0·008). Younger patients required significantly more lines of therapy during follow-up. The 10-year cumulative incidence of secondary malignancies in young and old patients was 0·205 and 0·287, respectively (P = 0·22). The incidence of secondary cancers in patients aged >40 years at diagnosis increased with the number of treatments for HCL (P = 0·018). These results highlight that young patients with HCL have shorter responses to treatment and require more lines of therapy to maintain disease control, while attaining similar long-term survival. This has implications in the design of future clinical trials given our findings that secondary malignancies increase with more chemotherapy exposure. © 2016 John Wiley & Sons Ltd.

  18. Prognostic Model for Predicting Survival of Patients With Metastatic Urothelial Cancer Treated With Cisplatin-Based Chemotherapy

    PubMed Central

    2013-01-01

    A prognostic model that predicts overall survival (OS) for metastatic urothelial cancer (MetUC) patients treated with cisplatin-based chemotherapy was developed, validated, and compared with a commonly used Memorial Sloan-Kettering Cancer Center (MSKCC) risk-score model. Data from 7 protocols that enrolled 308 patients with MetUC were pooled. An external multi-institutional dataset was used to validate the model. The primary measurement of predictive discrimination was Harrell’s c-index, computed with 95% confidence interval (CI). The final model included four pretreatment variables to predict OS: visceral metastases, albumin, performance status, and hemoglobin. The Harrell’s c-index was 0.67 for the four-variable model and 0.64 for the MSKCC risk-score model, with a prediction improvement for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .002). In the validation cohort, the c-indices for the four-variable and the MSKCC risk-score models were 0.63 (95% CI = 0.56 to 0.69) and 0.58 (95% CI = 0.52 to 0.65), respectively, with superiority of the four-variable model compared with the MSKCC risk-score model for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .02). PMID:23411591

  19. Validation and limitations of use of a breast cancer nomogram predicting the likelihood of non-sentinel node involvement after positive sentinel node biopsy.

    PubMed

    Alran, Séverine; De Rycke, Yann; Fourchotte, Virginie; Charitansky, Hélène; Laki, Fatima; Falcou, Marie Christine; Benamor, Myriam; Freneaux, Paul; Salmon, Rémy Jacques; Sigal-Zafrani, Brigitte

    2007-08-01

    Axillary lymph node dissection (ALND) for patients with positive sentinel lymph nodes (SLNs) is currently under discussion in the literature. The breast cancer nomogram (BCN), an online tool developed by the Memorial Sloan-Kettering Cancer Center (MSKCC), aims to predict the risk of positive non-SLN in SLN-positive patients. The purpose of this study was to test the accuracy of the nomogram on patients with macrometastatic and micrometastatic SLN-positive biopsy findings. Patient characteristics, tumor pathology, and positive SLN characteristics were collected on 588 consecutive patients who underwent completion ALND. The MSKCC BCN tool was used to calculate risk of metastases for all 588 cases that included a subgroup of the 213 patients with SLN micrometastases. The BCN was performed for positive SLN biopsy findings regardless of the method of metastasis detection. Evaluation of the BCN was performed by the area under the curve method. The BCN applied to all 588 patients achieved an area under the receiver operating characteristic curve (ROC) of .724 (range, .677-.771) compared with .76 in the MSKCC study. When the tool was applied solely to micrometastases found by hematoxylin and eosin staining and metastases found by immunohistochemistry, the area under the ROC was .538 (range, .423-.653). The MSKCC nomogram has been validated for all the patients having a metastatic SLN at the Institut Curie. However, this model was not reliably predictive for positive non-SLN in cases with micrometastic positive SLN.

  20. Which prediction models best identify additional axillary disease after a positive sentinel node biopsy for breast cancer?

    PubMed

    Berrang, Tanya S; Lesperance, Mary; Truong, Pauline T; Walter, Caroline; Hayashi, Allen H; Olivotto, Ivo A

    2012-06-01

    To determine which web-based model best identifies women at low risk of further axillary disease after a positive sentinel lymph node (SLN+) biopsy. 673 women with T1-2cN0M0 SNB+ breast cancer who underwent completion axillary dissection (AxD) were identified. A subgroup not eligible to avoid AxD as part of the Z0011 study was defined (Z0011 exclusion group). Predicted risk of further axillary disease was generated using seven web-based models. "Low risk" was defined as a ≤10% risk of further axillary disease. False negative ("low risk" prediction but AxD+) rates (FNRs), area under the receiver operating characteristic curve (AUC), and Brier score were determined for each model. 6 of 7 models identified "low risk" patients but FNRs ranged from 14 to 30%. The Stanford and Memorial Sloan-Kettering (MSKCC) models had the best FNRs. FNRs were lower with SLN micrometastasis (7-15%) and higher in the Z0011 exclusion group (21-41%). All models under-predicted further nodal disease in low risk patients and over-predicted in higher-risk patients. The Stanford and MSKCC models were able to identify women with SLN micrometastasis with a ≤10% FNR. Models were not able to accurately identify low risk women from a cohort that would have been excluded from Z0011.

  1. Traditional Chinese medicine use among Chinese immigrant cancer patients.

    PubMed

    Leng, Jennifer C F; Gany, Francesca

    2014-03-01

    Traditional Chinese Medicine (TCM) includes both herbal remedies and non-herbal practices. Chinese cancer patients are particularly at high risk for herb-drug interactions. Providers, both primary care physicians and oncologists, frequently do not ask patients about TCM use, which has potentially dangerous consequences. This study describes an assessment of TCM use while undergoing conventional cancer treatment, among a cohort of Chinese immigrant cancer patients in New York City. The Immigrant Health and Cancer Disparities Service at Memorial Sloan-Kettering Cancer Center assists underserved cancer patients through a patient navigation program, the Cancer Portal Project. Six questions related to TCM are included in the existing Portal Needs Assessment Intake. Mandarin- or Cantonese-speaking Portal patients enrolled between January 2010 and May 2012 were surveyed. One hundred nine Chinese-speaking patients were enrolled in the Portal Project during the study period. Forty-six completed the TCM questions. Ninety-six percent preferred to speak Mandarin, Cantonese, or Fujianese in the healthcare setting. Thirty-nine percent (n = 18) of the 46 participants reported using TCM since being diagnosed with cancer. Nearly all (n = 16) who used TCM reported using herbal medicines. Ten TCM users did not describe sharing their use with Western doctors. Eight (44%) of TCM users reported concurrently using TCM and conventional cancer treatment. Larger scale studies should further explore the concurrent use of TCM and conventional cancer treatment in this unique population. Future research should also address patient-provider communication related to the concurrent use of TCM and cancer treatment. This is also an important area of education for both patients and providers.

  2. Traditional Chinese Medicine Use among Chinese Immigrant Cancer Patients

    PubMed Central

    Leng, Jennifer C.F.; Gany, Francesca

    2017-01-01

    Background Traditional Chinese Medicine (TCM) includes both herbal remedies and non-herbal practices. Chinese cancer patients are at particularly high risk for herb-drug interactions. Providers, both primary care physicians (PCPs) and oncologists, frequently do not ask patients about TCM use, with potentially dangerous consequences. Objective This study describes an assessment of TCM use while undergoing conventional cancer treatment, among a cohort of Chinese immigrant cancer patients in New York City. Design and Participants The Immigrant Health and Cancer Disparities Service at Memorial Sloan-Kettering Cancer Center (MSKCC) assists underserved cancer patients through a patient navigation program, the Cancer Portal Project. Six questions related to TCM are included in the existing Portal Needs Assessment Intake. Mandarin or Cantonese speaking Portal patients enrolled between January 2010 and May 2012 were surveyed. Results 109 Chinese-speaking patients were enrolled in Portal during the study period. 46 completed the TCM questions. 96% preferred to speak Mandarin, Cantonese, or Fujianese in the healthcare setting. 39% (n=18) of the 46 participants reported using TCM since being diagnosed with cancer. Nearly all (n=16) who used TCM reported using herbal medicines. Ten TCM users did not describe sharing their use with Western doctors. Eight (44%) of TCM users reported concurrently using TCM and conventional cancer treatment. Conclusions Larger scale studies should further explore the concurrent use of TCM and conventional cancer treatment in this unique population. Future research should also address patient-provider communication related to concurrent use of TCM and cancer treatment. This is also an important area of education for both patients and providers. PMID:24072455

  3. Use and limitations of a nomogram predicting the likelihood of non-sentinel node involvement after a positive sentinel node biopsy in breast cancer patients.

    PubMed

    Kocsis, Lajos; Svébis, Mihály; Boross, Gábor; Sinkó, Mária; Maráz, Róbert; Rajtár, Mária; Cserni, Gábor

    2004-11-01

    After a positive sentinel lymph node (SLN) biopsy, some patients may be considered to have a very low risk of non-SLN involvement and could be candidates for axillary sparing. The aim of this study was to validate the nomogram created at the Memorial Sloan-Kettering Cancer Center (MSKCC) for the prediction of non-SLN involvement in an independent set of 140 patients with both positive SLNs and axillary dissection. The predicted proportions of positive non-SLNs were compared with the observed percentages of non-SLN metastasis. Although the SLN metastasis size and tumor size did influence the risk of non-SLN involvement, the correlation between the predicted and observed proportions was weaker for our patients (R: 0.84) than for the patients assessed at the MSKCC (R: 0.97). Differences were noted in the intraoperative assessment and in the final histology of the SLNs (imprints vs frozen sections and more detailed vs less detailed, respectively), and these could partly explain the lower level of the correlation. The nomogram could not be validated and was found to be of only limited use for the prediction of non-SLN involvement in patients operated on under similar, though not fully identical conditions. We therefore warn against the unvalidated use of this prediction tool.

  4. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance.

    PubMed

    Lou, Feiran; Huang, James; Sima, Camelia S; Dycoco, Joseph; Rusch, Valerie; Bach, Peter B

    2013-01-01

    At present, there is no consensus on the optimal strategy for follow-up care after curative resection for lung cancer. We sought to understand the patterns of recurrence and second primary lung cancer, and their mode of detection, after resection for early-stage non-small cell lung cancer in patients who were followed by routine surveillance computed tomography scan. We reviewed the outcomes of consecutive patients who underwent resection for early-stage non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center between 2004 and 2009. A total of 1294 consecutive patients with early-stage non-small cell lung cancer underwent resection. The median length of follow-up was 35 months. Recurrence was diagnosed in 257 patients (20%), and second primary lung cancer was diagnosed in 91 patients (7%). The majority of new primary cancers (85 [93%]) were identified by scheduled routine computed tomography scan, as were a smaller majority of recurrences (157 [61%]). During the first 4 years after surgery, the risk of recurrence ranged from 6% to 10% per person-year but decreased thereafter to 2%. Conversely, the risk of second primary lung cancer ranged from 3% to 6% per person-year and did not diminish over time. Additional testing after false-positive surveillance computed tomography scan results was performed for 329 patients (25%), but only 4 of these patients (0.3%) experienced complications as a result of subsequent invasive diagnostic procedures. Almost all second primary cancers and the majority of recurrences were detected by post-therapeutic surveillance computed tomography scan. The risk of recurrence for early-stage non-small cell lung cancer survivors persisted during the first 4 years after resection, and vigilance in surveillance should be maintained. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  5. Comparison of the Luminex xTAG RVP Fast assay and the Idaho Technology FilmArray RP assay for detection of respiratory viruses in pediatric patients at a cancer hospital.

    PubMed

    Babady, N Esther; Mead, Peter; Stiles, Jeffrey; Brennan, Carrie; Li, Haijing; Shuptar, Susan; Stratton, Charles W; Tang, Yi-Wei; Kamboj, Mini

    2012-07-01

    Respiratory viruses are increasingly recognized as serious causes of morbidity and mortality in immunocompromised patients. The rapid and sensitive detection of respiratory viruses is essential for the early diagnosis and administration of appropriate antiviral therapy, as well as for the effective implementation of infection control measures. We compared the performance of two commercial assays, xTAG RVP Fast (Luminex Diagnostics, Toronto, Canada) and FilmArray RVP (FA RVP; Idaho Technology, Salt Lake City, UT), in pediatric patients at Memorial Sloan-Kettering Cancer Center. These assays detect the following viruses: respiratory syncytial virus; influenza A and B viruses; parainfluenza viruses 1, 2, 3, and 4; human metapneumovirus; adenovirus; enterovirus-rhinovirus; coronaviruses NL63, HKU1, 229E, and OC43; and bocavirus. We tested a total of 358 respiratory specimens from 173 pediatric patients previously tested by direct fluorescence assay (DFA) and viral culture. The overall detection rate (number of positive specimens/total specimens) for viruses tested by all methods was 24% for DFA/culture, 45% for xTAG RVP Fast, and 51% for FA RVP. The agreement between the two multiplex assays was 84.5%, and the difference in detection rate was statistically significant (P < 0.0001). Overall, the FA RVP assay was more sensitive than the xTAG RVP Fast assay and had a turnaround time of approximately 1 h. The sensitivity, simplicity, and random-access platform make FA RVP an excellent choice for laboratory on-demand service with low to medium volume.

  6. Peripheral Neutrophil to Lymphocyte Ratio Improves Prognostication in Colon Cancer.

    PubMed

    Rashtak, Shahrooz; Ruan, Xiaoyang; Druliner, Brooke R; Liu, Hongfang; Therneau, Terry; Mouchli, Mohamad; Boardman, Lisa A

    2017-06-01

    We studied the role of peripheral neutrophil to lymphocyte ratio (NLR) on survival outcomes in colon and rectal cancer to determine if its inclusion improved prognostication within existing staging systems. Disease-free (DFS) and overall survival (OS) hazard ratios (HRs) of pretreatment NLR were calculated for 2536 patients with stage I to III colon or rectal cancer and adjusted for age, positive/total number of nodes, T stage, and grade. The association of NLR with clinicopathologic features and survival was evaluated and compared with the American Joint Committee on cancer (AJCC) TNM staging and Memorial Sloan Kettering Cancer Center (MSKCC) models. High NLR was significantly associated with worse DFS (HR, 1.36; 95% confidence interval [CI], 1.08-1.70; P = .009) and OS (HR, 1.65; 95% CI, 1.29-2.10; P < .0005) in all stages for patients with colon, but not rectal, cancer. High NLR was significantly associated with site-specific worse prognosis, which was stronger in the left versus right colon; an inverse relationship with grade was found. The impact of high NLR on DFS and OS occurred early, with the majority of deaths within 2 years following surgery. Adjusted HRs for 5-year and 2-year outcomes in colon cancer per each additional 2-unit increase in NLR were 1.15 (95% CI, 1.08-1.23) and 1.20 (95% CI, 1.10-1.30), respectively. The addition of NLR enhanced the prognostic utility of TNM (TNM alone vs. TNM + NLR: concordance index, 0.60 vs. 0.68), and MSKCC (MSKCC alone vs. MSKCC + NLR: concordance index, 0.71 vs. 0.73) models for colon cancer patients. NLR is an independent prognostic variable for nonmetastatic colon cancer that enhances existing clinical staging systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Physical and psychologic readjustment after mastectomy: an evaluation of Memorial Hospitals' PMRG program.

    PubMed

    Winick, L; Robbins, G F

    1977-02-01

    Memorial Hospital in New York City, the clinical section of the Memorial Sloan-Kettering Cancer Center, has developed a Post-Mastectomy Rehabilitation Group (PMRG) Program. The PMRG Program is comprised of a series of structured exercise, information, discussion, and group therapy sessions conducted by a social worker, nurse, physical therapist, and a volunteer from Reach to Recovery. The specific purposes of the program are to help a patient to begin to regain functional use of her arm and shoulder on the affected side, and to adapt functionally, psychologically, and emotionally to the loss of her breast and to the diagnosis of cancer in the shortest time possible. Approximately 1,700 women who underwent mastectomy participated in the program between 1970 and 1974. Some results and conclusions are: the patient's age and type of operation are related to physical recovery, resumption of normal activities, return to work, and emotional stress; 84% (661 of 790 patients) resumed normal activities within the four-month postoperative period; 74% (237 of 317 patients) returned to work (full time) within three months of their mastectomies; 13% (52 of 406 patients) experienced moderate or severe emotional stress; activity per se (any activity, doing something, keeping busy) affects readjustment; the apparent disadvantage of greater trauma with more extensive surgery may be more than compensated for by the relatively young age of that population, and the relatively less physical trauma and injury, resulting from simple mastectomies may be overshadowed by the patient's age and general physical condition; 98% (284 of 291 patients) reported the PMRG program helpful.

  8. The chronology of distress, anxiety, and depression in older prostate cancer patients

    PubMed Central

    Nelson, Christian J.; Weinberger, Mark I.; Balk, Eliana; Holland, Jimmie; Breitbart, William; Roth, Andrew J.

    2010-01-01

    Objective Current research suggests that older cancer patients report less distress compared to younger cancer patients. However, this research has generally not teased apart the differences between general distress, anxiety, and depression. Methods We conducted a secondary analysis of merged datasets using cross-sectional data on 736 men with prostate cancer (Mean Age 68±10 years of age, range 50 to 93). Approximately half the participants were recruited from doctors’ offices throughout the United States and the other half from Memorial Sloan-Kettering Cancer Center (New York, NY). Participants were asked to complete the Distress Thermometer, the Hospital Anxiety and Depression Scale (HADS), the FACT-P Quality of Life questionnaire, and a demographic questionnaire. Results Aging was related to reduced distress (r=−0.14), less anxiety (r=−0.22), and increased emotional quality of life (r= 0.16). In contrast, aging was associated with greater depressive symptoms in these cancer patients (r= 0.18). The mean depression scores of 5-year cohorts consistently trended upward. The significant association between age and depression remained after controlling for stage of disease, hormone therapy use, time since diagnosis, and social, physical and functional well-being. Conclusions Despite theoretical and empirical evidence that older cancer patients may cope more effectively than younger cancer patients, depressive symptoms remain an important concern for aging cancer patients and greater attention to this area is warranted. The increase in depression is in contrast to some findings in the general aging literature, raising the possibility that this trend is unique to older cancer patients. PMID:19738000

  9. A National Network to Advance the Field of Cancer and Female Sexuality

    PubMed Central

    Goldfarb, Shari B.; Abramsohn, Emily; Andersen, Barbara L.; Baron, Shirley R.; Carter, Jeanne; Dickler, Maura; Florendo, Judith; Freeman, Leslie; Githens, Katherine; Kushner, David; Makelarski, Jennifer A.; Yamada, Diane; Lindau, Stacy Tessler

    2013-01-01

    Introduction Understanding sexual health issues in cancer patients is integral to care for the continuously growing cancer survivor population. Aim To create a national network of active clinicians and researchers focusing on the prevention and treatment of sexual problems in woman and girls with cancer. Methods Interdisciplinary teams from the University of Chicago and Memorial Sloan-Kettering Cancer Center jointly developed the mission for a national conference to convene clinicians and researchers in the field of cancer and female sexuality. The invitee list was developed by both institutions and further iterated through suggestions from invitees. The conference agenda focused on three high-priority topics under the guidance of a professional facilitator. Breakout groups were led by attendees recognized by collaborators as experts in those topics. Conference costs were shared by both institutions. Main Outcome Measure Development of Scientific Working Groups (SWGs) Results One hundred two clinicians and researchers were invited to attend the 1st National Conference on Cancer and Female Sexuality. Forty-three individuals from 20 different institutions across 14 states attended, including representation from eight NCI-funded cancer centers. Attendees included PhD researchers (n=19), physicians (n=16), and other health care professionals (n=8). Breakout groups included: 1) Defining Key Life Course Sexuality Issues; 2) Building a Registry; and 3) Implementing Sexual Health Assessment. Breakout group summaries incorporated group consensus on key points and priorities. These generated six SWGs with volunteer leaders to accelerate future research and discovery: 1) Technology-Based Interventions; 2) Basic Science; 3) Clinical Trials; 4) Registries; 5) Measurement; and 6) Secondary Data Analysis. Most attendees volunteered for at least one SWG (n=35), and many volunteered for two (n=21). Conclusion This 1st National Conference demonstrated high motivation and broad

  10. History of International Workshop on Mini-Micro- and Nano- Dosimetry (MMND) and Innovation Technologies in Radiation Oncology (ITRO)

    NASA Astrophysics Data System (ADS)

    Rosenfeld, Anatoly B.; Zaider, Marco; Yamada, Josh; Zelefsky, Michael J.

    2017-01-01

    The biannual MMND (former MMD) - IPCT workshops was founded in collaboration between the Centre for Medical Radiation Physics, University of Wollongong and the Memorial Sloan Kettering Cancer Center (MSKCC) in 2001 and has become an important international multidisciplinary forum for the discussion of advanced quality assurance (QA) dosimetry technology for radiation therapy and space science, as well as advanced technologies for clinical cancer treatment.

  11. Bringing Precision Medicine to Community Oncologists.

    PubMed

    2017-01-01

    Quest Diagnostics has teamed up with Memorial Sloan Kettering Cancer Center and IBM Watson Health to offer IBM Watson Genomics to its network of community cancer centers and hospitals. This new service aims to advance precision medicine by combining genomic tumor sequencing with the power of cognitive computing.

  12. AACR precision medicine series: Highlights of the integrating clinical genomics and cancer therapy meeting.

    PubMed

    Maggi, Elaine; Montagna, Cristina

    2015-12-01

    The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice. The plenary sessions and panel discussions covered current platforms and sequencing approaches adopted for NGS assays of cancer genome at several national and international institutions, different approaches used to map and classify targetable sequence variants, and how information acquired with the sequencing of the cancer genome is used to guide treatment options. While challenges still exist from a technological perspective, it emerged that there exists considerable need for the development of tools to aid the identification of the therapy most suitable based on the mutational profile of the somatic cancer genome. The process to match patients to ongoing clinical trials is still complex. In addition, the need for centralized data repositories, preferably linked to well annotated clinical records, that aid sharing of sequencing information is central to begin understanding the contribution of variants of unknown significance to tumor etiology and response to therapy. Here we summarize the highlights of this stimulating four-day conference with a major emphasis on the open problems that the clinical genomics community is currently facing and the tools most needed for advancing this field. Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  13. Expression and Functional Role of Orphan Receptor GPR158 in Prostate Cancer Growth and Progression

    PubMed Central

    Patel, Nitin; Itakura, Tatsuo; Jeong, Shinwu; Liao, Chun-Peng; Roy-Burman, Pradip; Zandi, Ebrahim; Groshen, Susan; Pinski, Jacek; Coetzee, Gerhard A.; Gross, Mitchell E.; Fini, M. Elizabeth

    2015-01-01

    Prostate cancer (PCa) is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth is dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT). Eventually however, the disease progresses to castration-resistant prostate cancer (CRPC), a lethal form in need of more effective treatments. G-protein coupled receptors (GPCRs) comprise a large clan of cell surface proteins that have been implicated as therapeutic targets in PCa growth and progression. The findings reported here provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression. We found that GPR158 promotes PCa cell proliferation independent of androgen receptor (AR) functionality and that this requires its localization in the nucleus of the cell. This suggests that GPR158 acts by mechanisms different from other GPCRs. GPR158 expression is stimulated by androgens and GPR158 stimulates AR expression, implying a potential to sensitize tumors to low androgen conditions during ADT via a positive feedback loop. Further, we found GPR158 expression correlates with a neuroendocrine (NE) differentiation phenotype and promotes anchorage-independent colony formation implying a role for GPR158 in therapeutic progression and tumor formation. GPR158 expression was increased at the invading front of prostate tumors that formed in the genetically defined conditional Pten knockout mouse model, and co-localized with elevated AR expression in the cell nucleus. Kaplan-Meier analysis on a dataset from the Memorial Sloan Kettering cancer genome portal showed that increased GPR158 expression in tumors is associated with lower disease-free survival. Our findings strongly suggest that pharmaceuticals targeting GPR158 activities could represent a novel and innovative approach to the prevention and management of CRPC. PMID:25693195

  14. Expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression.

    PubMed

    Patel, Nitin; Itakura, Tatsuo; Jeong, Shinwu; Liao, Chun-Peng; Roy-Burman, Pradip; Zandi, Ebrahim; Groshen, Susan; Pinski, Jacek; Coetzee, Gerhard A; Gross, Mitchell E; Fini, M Elizabeth

    2015-01-01

    Prostate cancer (PCa) is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth is dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT). Eventually however, the disease progresses to castration-resistant prostate cancer (CRPC), a lethal form in need of more effective treatments. G-protein coupled receptors (GPCRs) comprise a large clan of cell surface proteins that have been implicated as therapeutic targets in PCa growth and progression. The findings reported here provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression. We found that GPR158 promotes PCa cell proliferation independent of androgen receptor (AR) functionality and that this requires its localization in the nucleus of the cell. This suggests that GPR158 acts by mechanisms different from other GPCRs. GPR158 expression is stimulated by androgens and GPR158 stimulates AR expression, implying a potential to sensitize tumors to low androgen conditions during ADT via a positive feedback loop. Further, we found GPR158 expression correlates with a neuroendocrine (NE) differentiation phenotype and promotes anchorage-independent colony formation implying a role for GPR158 in therapeutic progression and tumor formation. GPR158 expression was increased at the invading front of prostate tumors that formed in the genetically defined conditional Pten knockout mouse model, and co-localized with elevated AR expression in the cell nucleus. Kaplan-Meier analysis on a dataset from the Memorial Sloan Kettering cancer genome portal showed that increased GPR158 expression in tumors is associated with lower disease-free survival. Our findings strongly suggest that pharmaceuticals targeting GPR158 activities could represent a novel and innovative approach to the prevention and management of CRPC.

  15. Final Report - DOE Center for Laser Imaging and Cancer Diagnostics

    SciTech Connect

    Alfano, Robert R.; Koutcher, Jason A.

    2002-10-31

    This Final Report summarizes the significant progress made by the researchers, students and staff of the Center for Laser Imaging and Cancer Diagnostics (CLICD) from January 1998 through May 2002. During this period, the Center supported several projects. Most projects were proposed initially, some were added subsequently as their relevance and importance to the DOE mission became evident. DOE support has been leveraged to obtain continuing funding for some projects. Leveraged funds come from various sources, including NIH, Army, NSF and the Air Force. The goal of the Center was to develop laser-based instruments for use in the detection and diagnosis of major diseases, with an emphasis on detection and diagnosis of various cancers. Each of the supported projects is a collaborative effort between physicists and laser scientists and the City College of New York and noted physicians, surgeons, pathologists, and biologists located at medical centers in the Metropolitan area. The participating institutions were: City College of New York Institute for Ultrafast Lasers and Spectroscopy, Hackensack University Medical Center, Lawrence Livermore National Laboratory, Memorial Sloan Kettering Cancer Center, and New York Eye and Ear Institute. Each of the projects funded by the Center is grouped into one of four research categories: a) Disease Detection, b) Non-Disease Applications, c) New Diagnostic Tools, and, d) Education, Training, Outreach and Dissemination. The progress achieved by the multidisciplinary teams was reported in 51 publications and 32 presentations at major national conferences. Also, one U.S. patent was obtained and six U.S. patent applications have been filed for innovations resulting from the projects sponsored by the Center.

  16. American Society of Clinical Oncology

    MedlinePlus

    ... The 10th Joint MSKCC/HSS/IOR Course in Musculoskeletal Tumor Pathology and Clinical Oncology New York, New York, United ... The 10th Joint MSKCC/HSS/IOR Course in Musculoskeletal Tumor Pathology and Clinical Oncology Memorial Sloan Kettering Cancer Center ...

  17. Late effects and quality of life after chemo-radiation for the treatment of anal cancer.

    PubMed

    Knowles, Gillian; Haigh, Rachel; McLean, Catriona; Phillips, Hamish

    2015-10-01

    The aim of this study was to evaluate the late effects and quality of life of patients following chemo-radiation treatment for anal cancer. All surviving anal cancer patients treated within NHS Lothian between 1990 and 2007 were invited to participate. Data were collected using the EORTC QLQ-C30, the EORTC QLQ-CR38 and the Memorial Sloan-Kettering Cancer Centre Bowel Function Instrument (MSKCC). Overall response rate was 46% (n = 42); mean age 54.7 years and with a median time interval of 63.8 months between treatment and completion of the questionnaires. Thirty-five percent of the participants were 'rarely' or 'never' able to wait 15 min to get to the toilet; 50% were 'rarely' or 'never' able to control the passage of gas; 35% limited the types of solid foods they eat; 22% had leakage of stool during the day; 39% required to use a protective pad and 29% altered their daily activities because of bowel function 'always' or 'most of the time'. Seventeen percent of patients reported financial difficulties ('quite a bit' and 'very much'). Both men and women reported high symptomology for sexual problems with a median score of 83.3 (50.0. 100.0). This study has shown that in a sub-set of patients treated with chemo-radiation for anal cancer, persistent treatment related issues are reported at a medium time interval of 5.3 years. Further work is now required to understand the impact of symptoms on day-to-day life and the challenges that people face in managing these inter-related and complex problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Ovarian vein thrombosis after debulking surgery for ovarian cancer: epidemiology and clinical significance.

    PubMed

    Mantha, Simon; Sarasohn, Debra; Ma, Weining; Devlin, Sean M; Chi, Dennis S; Roche, Kara Long; Suidan, Rudy S; Woo, Kaitlin; Soff, Gerald A

    2015-08-01

    Ovarian vein thrombosis is associated with pregnancy and pelvic surgery. Postpartum ovarian vein thrombosis is associated with infection and a high morbidity rate and is treated with anticoagulant and intravenous antibiotic therapy. The natural history of such thrombotic events after debulking surgery for ovarian cancer has not been well described. Our objective was to characterize the presentation and outcomes for patients with this condition at our institution. We conducted a retrospective study of patients who underwent surgical debulking for ovarian cancer at Memorial Sloan Kettering Cancer Center between the years 2001 and 2010. Patients were included if contrast computed tomography scans of both the abdomen and pelvis were performed within 12 weeks before and 12 weeks after the surgery. The images were reviewed to assess for the presence and extent of a new postoperative ovarian vein thrombosis. When available, subsequent studies were assessed for thrombus progression. Medical records were reviewed to determine whether anticoagulation was used for treatment of the thrombotic episode and to record the occurrence of any new significant venous thromboembolic event in the next year. One hundred fifty-nine patients had satisfactory imaging. New ovarian vein thrombosis was a common complication of debulking surgery, as found in 41 of patients (25.8%). Only 5 women with ovarian vein thrombosis were started on anticoagulation, of which 2 individuals had an independent venous thromboembolic event as indication for treatment. Only 2 of the ovarian vein thromboses (4.9%) progressed to the inferior vena cava or left renal vein on subsequent scan. The estimated cumulative incidence of venous thromboembolism 1 year after the first postoperative scan was 17.1% for patients in the new ovarian vein thrombosis group vs 15.3% of individuals for the group without a postoperative ovarian vein thrombosis (P = .78). Ovarian vein thrombosis is commonly encountered after debulking

  19. The relation of visualization of internal mammary lymph nodes on lymphoscintigraphy to axillary lymph node metastases in breast cancer.

    PubMed

    Kim, Heeyoung; Shin, Myung-Jun; Kim, Seong-Jang; Kim, In-Joo; Park, Ilkyu

    2014-12-01

    A few studies about lymphoscintigraphy in breast cancer patients have reported a correlation between decreased sentinel lymph node (LN) uptake and increased risk of axillary involvement with the hypothesis of blocked lymphatic passage of radiotracers by metastatic burden. This study is designed to investigate whether the visible internal mammary LN of lymphoscintigraphy (IM-LPS) is related to axillary LN metastasis, rather than identifying sentinel LN in the internal mammary area. We retrospectively reviewed medical records of 401 breast cancer patients who underwent sentinel lymphoscintigraphy using Tc-99m phytate and subsequent axillary LN dissection. The IM-LPS was divided into positive or negative groups, and axillary lymphoscintigraphy (A-LPS) was visually graded into four groups according to the method suggested by Lee et al. (1) To evaluate the relation of positive IM-LPS and A-LPS pattern with axillary LN metastasis, multivariate logistic regression analysis was done with covariates of Memorial Sloan-Kettering Cancer Center model. Positive IM-LPS was found in 32 patients. On the univariate logistic regression analysis, positive IM-LPS (p=0.01) and A-LPS pattern (p<0.05) successfully predicted the axillary LN status. On the multivariate logistic regression model, positive IM-LPS (OR 2.6362; 95% CI 1.0382-6.6938; p=0.04) and group II A-LPS (OR 1.9773; 95% CI 1.1336-3.4491; p=0.01) remained statistically significant variables for the predictor of axillary LN metastasis. This study suggests that IM-LPS and A-LPS pattern might be useful to show the burden of axillary LN metastasis in breast cancer patients, as an indicator of altered lymphatic pathway.

  20. Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers.

    PubMed

    Eng, Juliana; Hsu, Meier; Chaft, Jamie E; Kris, Mark G; Arcila, Maria E; Li, Bob T

    2016-09-01

    Human epidermal growth factor receptor 2 (HER2, ERBB2) mutations occur in 3% of lung adenocarcinomas. While case reports and series have shown activity of HER2 targeted agents in these patients, little is known about outcomes of chemotherapies. Patients with stage IV HER2-mutant lung cancers at Memorial Sloan Kettering were reviewed. Patient demographics, types of HER2 mutations, duration of systemic treatments and survival were analyzed. We identified 38 patients with HER2-mutant lung cancers: median age 62; majority were women (n=24), never smokers (n=22), and all had adenocarcinomas. A 12 base pair in-frame insertion YVMA in exon 20 (p.A775_G776insYVMA) was present in 24 (63%, 95% CI 46-78%) patients. In addition, there were four 9 base pair insertions, one 6 base pair insertion, and five 3 base pair insertions in exon 20, and four single bp substitutions (exon 20 L755F, V777L, D769H, exon 8 S310F). The median overall survival from date of diagnosis of stage IV disease was 2.3 years (95% CI 1.2-2.6). The median duration of chemotherapy was 4.3 months (68 treatments, range 0-21 months): 6.2 months for pemetrexed ±platinum/bevacizumab, 4 months for taxane ±platinum/bevacizumab, 2.6 months for gemcitabine, 3.5 months for vinorelbine. The median duration of HER2 tyrosine kinase inhibitors was 2.2 months (28 treatments, range 0.3-16.3 months). As we search for better targeted therapies for patients with HER2-mutant lung cancers, chemotherapy remains an important component of care.

  1. Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

    PubMed Central

    Deal, Allison M.; Kris, Mark G.; Scher, Howard I.; Hudis, Clifford A.; Sabbatini, Paul; Rogak, Lauren; Bennett, Antonia V.; Dueck, Amylou C.; Atkinson, Thomas M.; Chou, Joanne F.; Dulko, Dorothy; Sit, Laura; Barz, Allison; Novotny, Paul; Fruscione, Michael; Sloan, Jeff A.; Schrag, Deborah

    2016-01-01

    Purpose There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. Methods We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. Results Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. Conclusion Clinical benefits were associated with symptom self-reporting during cancer care. PMID:26644527

  2. Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

    SciTech Connect

    Krengli, Marco; Terrone, Carlo; Ballare, Andrea; Loi, Gianfranco; Tarabuzzi, Roberto; Marchioro, Giansilvio; Beldi, Debora; Mones, Eleonora; Bolchini, Cesare R.T.; Volpe, Alessandro; Frea, Bruno

    2010-03-15

    Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Administration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4-8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15-45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

  3. Bladder cancer in men and women treated by radiation therapy and/or radical cystectomy.

    PubMed

    Batata, M A; Chu, F C; Hilaris, B S; Whitmore, W F; Kim, Y S; Lee, M Z

    1981-07-01

    Four-hundred fifty-one patients with bladder cancer, 348 men and 103 women, were treated by radiation therapy and/or radical cystectomy during the last two decades at Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment in 98 men and 39 women. Radical radiation therapy to an average tumor dose of 6,000 rad in six weeks was given to 79 men and 30 women +/- one year before salvage cystectomy was done for recurrent or persistent tumors. Planned preoperative irradiation was delivered to the true pelvis either 4,000 rad in four weeks in 95 men and 24 women or 2,000 rad in one week in 76 men and 10 women +/- six weeks and two days, respectively, before radical cystectomy. Over-all survival and recurrence results in both sexes were similar, 40 per cent of men and 36 per cent of women were alive at five years without recurrence, 45 per cent of men and 48 per cent of women died in five or more years with local and/or distant recurrences, and 21 per cent of men and 15 per cent of women died before five years from causes other than cancer recurrence. Higher five-year survival for high clinical stage B2 to D1 tumors was noted similarly in the irradiated men (30 per cent) and women (37 per cent) than in the cystectomy alone patients (19 per cent in men and 4 per cent in women). Similar survival rates (52 to 57 per cent) were observed in men and women with low clinical stage O to B1 tumors treated with or without irradiation.

  4. Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial.

    PubMed

    Basch, Ethan; Deal, Allison M; Kris, Mark G; Scher, Howard I; Hudis, Clifford A; Sabbatini, Paul; Rogak, Lauren; Bennett, Antonia V; Dueck, Amylou C; Atkinson, Thomas M; Chou, Joanne F; Dulko, Dorothy; Sit, Laura; Barz, Allison; Novotny, Paul; Fruscione, Michael; Sloan, Jeff A; Schrag, Deborah

    2016-02-20

    There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. Clinical benefits were associated with symptom self-reporting during cancer care. © 2015 by American Society of Clinical Oncology.

  5. The TNM system (version 7) is the most accurate staging system for the prediction of loss of life expectancy in differentiated thyroid cancer.

    PubMed

    Tanase, Karina; Thies, Elena-Daphne; Mäder, Uwe; Reiners, Christoph; Verburg, Frederik A

    2015-03-04

    Many prognostic systems have been developed for differentiated thyroid cancer. It is unclear which one of these performs 'best'. Our aim was to compare staging systems applicable to our patient database to identify which best predicts DTC-related loss of life expectancy and DTC-specific mortality. Database study of patients with DTC treated in our centre between 1978 (earliest available data) up to and including 1 July 2014. All were staged in accordance with the AMES, Clinical Class, Memorial Sloan Kettering, Ohio State University, TNM versions 5 and 6/7, University of Alabama, University of Münster and qTNM systems. A total of 2257 patients with differentiated thyroid cancer. Loss of life expectancy expressed as relative survival and thyroid cancer-specific mortality. Comparison was based on P values of univariate Cox regression analyses as well as analysis of the proportion of variance explained (PVE). Median available follow-up time was 7·2 years (range: 0-35·1 years). Three hundred and twenty-seven patients died, 149 of whom died of DTC. Version 7 of the TNM system was best for predicting DTC-related mortality (P = 7·1 × 10(-52) ; PVE = 0·296), followed by TNM version 5 (P = 6·7 × 10(-44) ; PVE = 0·255). For prediction of loss of life expectancy, version 7 of the TNM system was also best, closely followed by the Clinical Class system (P both < 2 × 10(-16) ). The UICC/AJCC TNM system version 7 outperforms other prognostic classification systems based on extent of disease at the start of treatment both for prediction of differentiated thyroid cancer-related death and for prediction of loss life expectancy. © 2015 John Wiley & Sons Ltd.

  6. Patterns of Utilization of Adjuvant Radiotherapy and Outcomes in Black Women After Breast Conservation at a Large Multidisciplinary Cancer Center;Black women; Breast cancer; Radiotherapy; RT; Breast conservation

    SciTech Connect

    Edwards-Bennett, Sophia M.; Jacks, Lindsay M.; McCormick, Beryl; Zhang, Zhigang; Azu, Michelle; Ho, Alice; Powell, Simon; Brown, Carol

    2011-07-15

    Purpose: Population-based studies have reported that as many of 35% of black women do not undergo radiotherapy (RT) after breast conservation surgery (BCS). The objective of the present study was to determine whether this trend persisted at a large multidisciplinary cancer center, and to identify the factors that predict for noncompliance with RT and determine the outcomes for this subset of patients. Methods and Materials: Between January 2002 and December 2007, 83 black women underwent BCS at Memorial Sloan-Kettering Cancer Center and were therefore eligible for the present study. Of the 83 women, 38 (46%) had Stage I, 38 (46%) Stage II, and 7 (8%) Stage III disease. Of the study cohort, 31 (37%) had triple hormone receptor-negative tumors. RT was recommended for 81 (98%) of the 83 patients (median dose, 60 Gy). Results: Of the 81 women, 12 (15%) did not receive the recommended adjuvant breast RT. Nonreceipt of chemotherapy (p = .003) and older age (p = .009) were associated with nonreceipt of RT. With a median follow-up of 70 months, the 3-year local control, locoregional control, recurrence-free survival, disease-free survival, and overall survival rate was 99% (actuarial 5-year rate, 97%), 96% (actuarial 5-year rate, 93%), 95% (actuarial 5-year rate, 92%), 92% (actuarial 5-year rate, 89%), and 95% (actuarial 5-year rate, 91%), respectively. Conclusion: We found a greater rate of utilization adjuvant breast RT (85%) among black women after BCS than has been reported in recent studies, indicating that excellent outcomes are attainable for black women after BCS when care is administered in a multidisciplinary cancer center.

  7. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer.

    PubMed

    Cercek, Andrea; Goodman, Karyn A; Hajj, Carla; Weisberger, Emily; Segal, Neil H; Reidy-Lagunes, Diane L; Stadler, Zsofia K; Wu, Abraham J; Weiser, Martin R; Paty, Philip B; Guillem, Jose G; Nash, Garrett M; Temple, Larissa K; Garcia-Aguilar, Julio; Saltz, Leonard B

    2014-04-01

    Standard therapy for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy and postoperative chemotherapy. At Memorial Sloan-Kettering Cancer Center (MSKCC) the authors began offering FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as initial treatment for patients with high-risk LARC to target micrometastases while treating the primary tumor. The purpose of this study is to report the safety and efficacy of initial FOLFOX given before chemoradiotherapy on tumor downsizing and pathologic complete response (pathCR) in LARC. The records of patients with stage II/III rectal cancer treated at MSKCC between 2007 and 2012 were reviewed. Of approximately 300 patients with LARC treated at MSKCC, 61 received FOLFOX as initial therapy. Of these 61 patients, 57 received induction FOLFOX (median 7 cycles) followed by chemoradiation, and 4 experienced an excellent response, declined chemoradiation, and underwent total mesorectal excision (TME). Twelve of the 61 patients did not undergo TME: 9 had a complete clinical response (CCR), 1 declined despite persistent tumor, 1 declined because of comorbidities, and 1 developed metastatic disease. Among the 61 patients receiving initial FOLFOX, 22 (36%) had either a pathCR (n=13) or a CCR (n=9). Of the 49 patients who underwent TME, all had R0 resections and 23 (47%) had tumor response greater than 90%, including 13 (27%) who experienced a pathCR. Of the 28 patients who received all 8 cycles of FOLFOX, 8 experienced a pathCR (29%) and 3 a CCR (11%). No serious adverse events occurred that required a delay in treatment during FOLFOX or chemoradiation. FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.

  8. Visible ink: A flexible and individually tailored writing intervention for cancer patients

    PubMed Central

    CORNER, GEOFFREY W.; JHANWAR, SABRINA M.; KELMAN, JUDITH; PESSIN, HAYLEY; STEIN, EMMA; BREITBART, WILLIAM

    2017-01-01

    Objectives Subjective reports on the effectiveness of and satisfaction with writing interventions in medical populations have indicated that they can have a profound impact on patients. Further, past research on these programs has demonstrated that they can lead to a number of different positive outcomes depending on the personal characteristics of the participating patients and the type of writing with which they are tasked. For this reason, a flexible and individually tailored writing intervention may be particularly effective for patients, molding its approach to their desires and backgrounds. This paper examines Visible Ink, a writing program for cancer patients at Memorial Sloan-Kettering Cancer Center (MSKCC) that follows this model. Methods At Visible Ink’s First Fall Writing Festival in November 2012, an optional survey was provided to all program participants in attendance, capturing both quantitative and qualitative information on patient experiences in the program. Twenty-nine surveys were completed. Results The program appears to have a variety of positive effects, including fostering personal growth and providing a positive distraction. Respondents reported that they write in a number of different genres on topics both related and not related to their illnesses, which supports the flexible model of the program. All respondents indicated that they would recommend the program to others, and satisfaction with the program’s general approach (i.e., individualized work with a writing coach) was unanimous. A few areas for potential improvement were also identified, most of which involved expanding the services and events offered by the program. Significance of results Despite the limitations of this survey (e.g., small sample size and low response rate), its results support the promise of the Visible Ink model and demonstrate participants’ satisfaction with the program. Future research can more thoroughly examine Visible Ink’s effectiveness, and

  9. Visible ink: A flexible and individually tailored writing intervention for cancer patients.

    PubMed

    Corner, Geoffrey W; Jhanwar, Sabrina M; Kelman, Judith; Pessin, Hayley; Stein, Emma; Breitbart, William

    2015-04-01

    Subjective reports on the effectiveness of and satisfaction with writing interventions in medical populations have indicated that they can have a profound impact on patients. Further, past research on these programs has demonstrated that they can lead to a number of different positive outcomes depending on the personal characteristics of the participating patients and the type of writing with which they are tasked. For this reason, a flexible and individually tailored writing intervention may be particularly effective for patients, molding its approach to their desires and backgrounds. This paper examines Visible Ink, a writing program for cancer patients at Memorial Sloan-Kettering Cancer Center (MSKCC) that follows this model. At Visible Ink's First Fall Writing Festival in November 2012, an optional survey was provided to all program participants in attendance, capturing both quantitative and qualitative information on patient experiences in the program. Twenty-nine surveys were completed. The program appears to have a variety of positive effects, including fostering personal growth and providing a positive distraction. Respondents reported that they write in a number of different genres on topics both related and not related to their illnesses, which supports the flexible model of the program. All respondents indicated that they would recommend the program to others, and satisfaction with the program's general approach (i.e., individualized work with a writing coach) was unanimous. A few areas for potential improvement were also identified, most of which involved expanding the services and events offered by the program. Despite the limitations of this survey (e.g., small sample size and low response rate), its results support the promise of the Visible Ink model and demonstrate participants' satisfaction with the program. Future research can more thoroughly examine Visible Ink's effectiveness, and additional resources could enable the program to expand.

  10. Geriatric Assessment as a Predictor of Delirium and Other Outcomes in Elderly Patients With Cancer.

    PubMed

    Korc-Grodzicki, Beatriz; Sun, Sung W; Zhou, Qin; Iasonos, Alexia; Lu, Bryan; Root, James C; Downey, Robert J; Tew, William P

    2015-06-01

    This study aimed to describe the implementation of preoperative geriatric assessment (GA) in patients undergoing major cancer surgery and to determine predictors of postoperative delirium. Geriatric surgical patients have unique vulnerabilities and are at increased risk of developing postoperative delirium. Geriatricians at Memorial Sloan Kettering Cancer Center risk-stratify surgical patients with solid tumors, ages 75 years and older, using preoperative GA, which includes basic and instrumental activities of daily living (ADLs, IADLs), cognition (Mini-Cog test), history of falls, nutritional state, and comorbidities (Charlson Comorbidity Index). The Geriatrics Service evaluates patients for postoperative delirium using the confusion assessment method. A retrospective review was performed. The associations between GA and postoperative outcomes were evaluated. Univariate logistic regression analysis was performed to determine the predictive value of GA for postoperative delirium, and a multivariate model was built. In total, 416 patients who received preoperative evaluation by the Geriatrics Service between September 1, 2010, and December 31, 2011, were included. Delirium occurred in 19% of patients. Patients with delirium had longer length of hospital stay (P < 0.001) and greater likelihood of discharge to a rehabilitation facility (P < 0.001). Charlson Comorbidity Index score, history of falls, dependent on IADL, and abnormal Mini-Cog test results predicted postoperative delirium on univariate analysis. Developed using a stepwise selection method, a multivariate model to predict delirium is presented including Charlson Comorbidity Index score (P = 0.032), dependence IADLs (P = 0.011), and falls history (P = 0.056). Preoperative GA is feasible and may achieve a better understanding of older patients' perioperative risks, including delirium.

  11. Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer

    PubMed Central

    McNamara, William F.; Wang, Laura Y.; Palmer, Frank L.; Nixon, Iain J.; Shah, Jatin P.; Patel, Snehal G.; Ganly, Ian

    2016-01-01

    Background The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence. Methods A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method. Results A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001). Conclusion Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease. PMID:26994486

  12. Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer.

    PubMed

    McNamara, William F; Wang, Laura Y; Palmer, Frank L; Nixon, Iain J; Shah, Jatin P; Patel, Snehal G; Ganly, Ian

    2016-06-01

    The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence. A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method. A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001). Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Indocyanine green fluorescence imaging of lymph nodes during robotic-assisted laparoscopic operation for endometrial cancer. A prospective validation study using a sentinel lymph node surgical algorithm.

    PubMed

    Hagen, Bjørn; Valla, Marit; Aune, Guro; Ravlo, Merethe; Abusland, Anne Britt; Araya, Elisabeth; Sundset, Marit; Tingulstad, Solveig

    2016-12-01

    A sentinel lymph node (SLN) strategy may have particular value in endometrial cancer (EC) because a therapeutic effect of lymphadenectomy per se is unproven. The aim was to evaluate indocyanine green (ICG) and near-infrared (NIR) fluorescence mapping using a surgical algorithm. From November 2012 through December 2015, women with apparently early stage EC underwent robot-assisted laparoscopic hysterectomy including ICG fluorescence SLN mapping following the Memorial Sloane Kettering Cancer Center (MSKCC) surgical algorithm. Among 108 patients included, ≥1 SLNs was identified in 104 (96%), bilaterally in 84 (78%) and unilaterally in 20 patients (18%). Four patients failed SLN mapping. All SLN-positive patients had pelvic SLNs. Median number of nodes were 4.0 and 6.0 (p<0.001), when SLNs only and SLNs plus non-SLNs were removed, respectively. Lymph node metastases were detected in 17 patients (16%). One patient who failed SLN mapping had a non-SLN metastasis. The remaining 16 patients had metastases in SLNs, 12 in SLNs only and four in both SLNs and non-SLNs. Routine pathology detected 75% of patients with cancer positive SLNs while 25% were based on extended pathology. Lymph node metastases were found among 9% with low-, 11% with intermediate- and 32% with high-risk profiles, respectively. We have reproduced the high total and bilateral SLN mapping using cervical ICG injection and NIR fluorescence. Practical application of the MSKCC algorithm allowed high lymph node metastasis detection in combination with a low extent of lymph node removal. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Advising patients on the use of non-herbal nutritional supplements during cancer therapy: a need for doctor-patient communication.

    PubMed

    Ben-Arye, Eran; Polliack, Aaron; Schiff, Elad; Tadmor, Tamar; Samuels, Noah

    2013-12-01

    Many cancer patients are using non-herbal nutritional supplements (NHNS), often without informing their oncologists. To review the literature and summarize the beneficial effects and safety of NHNS in the prevention and reduction of treatment-related symptoms. Databases were searched for randomized, controlled clinical trials (Jadad score ≥ 2) using AltHealthWatch, Cochrane Database of Systematic Reviews, Embase, MEDLINE, Memorial Sloan-Kettering Integrative Medicine Service Database, Natural Standard Database, and PubMed. The key words searched were the following: alternative and/or complementary medicine, nutritional and/or dietary supplements, quality of life, symptoms and/or side effects, specific toxicities (e.g., neuropathy, mucositis), and specific supplements (e.g., vitamin E, glutamine, etc.). A number of NHNS products were found to be effective. The incidence and severity of peripheral sensory neuropathy associated with taxane-agents such as paclitaxel can be reduced with vitamin E, glutamine, and acetyl-L-carnitine. Vitamin E and glutamine also have been shown to reduce oral mucositis resulting from radiation and chemotherapy, and glutamine and probiotics can reduce chemotherapy-induced diarrhea. There is a need to develop an open and nonjudgmental dialogue between oncologists and cancer patients, addressing the needs of the patient while dealing with issues related to the efficacy and safety of these products. Referral of patients to an integrative medicine consultant may help achieve these goals, providing both parties with the option of reaching an informed and respectful decision about treatment. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  15. Improvement in pain after lumbar surgery in cancer patients with mechanical radiculopathy.

    PubMed

    Moliterno, Jennifer; Veselis, Clinton A; Hershey, Michael A; Lis, Eric; Laufer, Ilya; Bilsky, Mark H

    2014-10-01

    Lumbar metastases can result in spinal instability and mechanical radiculopathy, characterized by radicular pain produced by axial loading. This pain pattern represents a definitive symptom of neoplastic instability and may serve as a reliable indication for surgical stabilization. We examined the results of surgical decompression and fixation in the treatment of mechanical radiculopathy. A retrospective clinical study. An internally maintained spine neurosurgery database was queried between February 2002 and April 2010. Patients were identified and deemed eligible for inclusion in this study based on the presence of all the following: metastatic tumor, lumbar surgery, and lumbar radiculopathy. Visual analog scale (VAS) of pain and Eastern Cooperative Oncology Group (ECOG) status. The Memorial Sloan-Kettering Cancer Center Department of Neurosurgery operative database was queried over an 8-year period to identify all patients with spinal metastases who underwent lumbar surgery. Only patients whose operative indication included mechanical radiculopathy were included. Pre- and postoperative pain was assessed with the VAS of pain, whereas pre- and postoperative performance status was evaluated using the ECOG. Fifty-five patients were included in the cohort. L2 and L3 were the most common levels involved, and most patients underwent multilevel posterior decompression and instrumented fusion. After surgery, 98% of patients reported pain relief. A significant difference between average pre- and postoperative pain scores was found (p<.01). Overall, 41.5% of patients experienced improvement in their ECOG score postoperatively. Mechanical radiculopathy in patients with spinal metastases represents a highly reliable surgical indication. Spinal decompression and fixation is an effective treatment for pain palliation in this patient population. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Regional Differences in Gallbladder Cancer Pathogenesis: Insights from a Comparison of Cell Cycle-Regulatory, PI3K, and Pro-Angiogenic Protein Expression

    PubMed Central

    Butte, Jean M.; Torres, Javiera; Veras, Emanuela F.; Matsuo, Kenichi; Gönen, Mithat; D’Angelica, Michael I.; Waugh, Enrique; Meneses, Manuel; Inayama, Yoshiyaki; Fong, Yuman; DeMatteo, Ronald P.; De La Fuente, Hernan; Endo, Itaru; Klimstra, David S.; Jarnagin, William R.

    2014-01-01

    Background The variable incidence of gallbladder cancer (GBCA) suggests regional pathogenetic differences. This study compares cell cycle-regulatory, angiogenesis-related, and PI3K pathway protein expression in GBCAs from three continents. Methods Immunohistochemical expression of several proteins was assessed, correlated with clinicopathologic variables, and compared among centers from Chile (Fundación Arturo López Pérez [FALP]), Japan (Yokohama City University [YCU]), and the United States (Memorial Sloan-Kettering Cancer Center [MSKCC]). Hierarchical clustering was used to partition the data based on protein-expression and treatment center. Results Tissue from 117 patients (MSKCC = 76; FALP = 22; YCU = 19) was analyzed. Mdm2 overexpression was seen only at MSKCC (p < 0.0001). Absence of p21 (p = 0.03) and VEGFR2 (p = 0.018) were more common and p27 expression was less frequent (p = 0.047) in tumors from YCU. Ki-67 labeling index in YCU tumors (median = 10) was two-thirds lower than at other centers. On hierarchical clustering analysis, all YCU patients (p = 0.017) and those with early tumors (p = 0.017) clustered separately from MSKCC. Median disease-specific survival after curative intent (R0) resection was 27 months and was similar among centers (p = 0.9). Median disease-specific survival of patients with early tumors was 28.4 months and was higher at YCU (not reached, p = 0.06). Conclusions Cell cycle-regulatory protein expression patterns of YCU tumors differed from those treated at FALP and MSKCC. The differential clustering of protein expression and survival in patients with early tumors suggest regional differences in pathogenesis and disease biology. PMID:23212762

  17. Reliability and Validity of a Survey to Measure Bowel Function and Quality of Life in Long-term Rectal Cancer Survivors

    PubMed Central

    Wendel, Christopher S.; Grant, Marcia; Herrinton, Lisa; Temple, Larissa K. F.; Hornbrook, Mark C.; McMullen, Carmit K.; Bulkley, Joanna E.; Altschuler, Andrea; Krouse, Robert S.

    2014-01-01

    Purpose Examine reliability and validity of a specialized health-related quality of life questionnaire for rectal cancer (RC) survivors (≥5 years post diagnosis). Methods We mailed 1,063 Kaiser Permanente (KP) RC survivors (313 ostomy, 750 anastomosis) a questionnaire containing the Modified City of Hope Quality of Life-Ostomy (mCOH-QOL-O), SF-12v2, Duke–UNC Functional Social Support Questionnaire (FSSQ), and Memorial Sloan-Kettering Cancer Center Bowel Function Index (BFI). We adapted certain BFI items for use by subjects with intestinal ostomies. We evaluated reliability for all instruments with inter-item correlations and Cronbach’s alpha. We assessed construct validity only for the BFI in the ostomy group, because such use has not been reported. Results The overall response rate was 60.5% (577 respondents/953 eligible). Compared to nonresponders, participants were on average 2 years younger and more likely non-Hispanic white, resided in educationally nondeprived areas, and had KP membership through a group. The mCOH-QOL-O, SF-12, and FSSQ were found to be highly reliable for RC survivors. In the ostomy group, BFI Urgency/Soilage and Dietary subscales were found to be reliable, but Frequency was not. Factor analysis supported the construct of Urgency/Soilage and Dietary subscales in the ostomy group, although one item had a moderate correlation with all three factors. The BFI also demonstrated good concurrent validity with other instruments in the ostomy group. Conclusions With possible exception of the BFI Frequency subscale in populations with ostomies, components of our survey can be used for the entire population of RC survivors, no matter whether they received anastomosis or ostomy. PMID:24890826

  18. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma

    PubMed Central

    Yeh, Yi-Chen; Kadota, Kyuichi; Nitadori, Jun-ichi; Sima, Camelia S.; Rizk, Nabil P.; Jones, David R.; Travis, William D.; Adusumilli, Prasad S.

    2016-01-01

    OBJECTIVES We investigated the role of the 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) classification in predicting occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. METHODS We reviewed lung adenocarcinoma patients who had clinically N2-negative status, were evaluated by preoperative positron emission tomography combined with computed tomography (PET/CT) and had undergone lobectomy or pneumonectomy at Memorial Sloan Kettering Cancer Center (n = 297). Tumours were classified according to the 2011 IASLC/ATS/ERS classification. The associations between occult lymph node metastasis and clinicopathological variables were analysed using Fisher's exact test and logistic regression analysis. RESULTS Thirty-two (11%) cN0-1 patients had occult mediastinal lymph node metastasis (pN2) whereas 25% of cN1 patients had pN2 disease. Increased micropapillary pattern was associated with increased risk of pN2 disease (P = 0.001). On univariate analysis, high maximum standard uptake value of the primary tumour on PET/CT (P = 0.019) and the presence of micropapillary (P = 0.014) and solid pattern (P = 0.014) were associated with occult pN2 disease. On multivariable analysis, micropapillary pattern was positively associated with risk of pN2 disease (odds ratio = 3.41; 95% confidence intervals = 1.42–8.19; P = 0.006). CONCLUSIONS The presence of micropapillary pattern is an independent predictor of occult mediastinal lymph node metastasis. Our observations have potential therapeutic implications for management of early-stage lung adenocarcinoma. PMID:26377636

  19. Multicenter prospective evaluation of the reliability of the combined use of two models to predict non-sentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: the MSKCC nomogram and the Tenon score. Results of the NOTEGS study.

    PubMed

    Rouzier, Roman; Uzan, Catherine; Rousseau, Alexandra; Guillot, Eugénie; Zilberman, Sonia; Meyer, Charles; Estevez, Pablo; Dupre, Pierre-Francois; Kere, David; Doridot, Virginie; D'halluin, Gauthier; Fritel, Xavier; Pouget, Nicolas; Jankowski, Clémentine; Mazouni, Chafika; Simon, Tabassome; Coutant, Charles

    2017-04-25

    The purpose of this study was to prospectively evaluate the combined use of The Memorial Sloan Kettering Cancer Center nomogram and Tenon score to select, in patients with metastatic sentinel lymph node (SN), those at low risk of metastatic non-SN for whom additional axillary lymph node dissection (ALND) could be avoided. From January 2011 to July 2012, a prospective non-interventional nationwide study was conducted (NCT01509963). We sought to identify the false reassurance rate (FRR, a negative test result is false) in patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 (low risk): the proportion of patients with metastatic non-SN at additional ALND. Our hypothesis was that these patients would have a FRR⩽5%. Data on 2822 patients with breast cancer from 53 institutions were prospectively recorded. At least one SN was metastatic (isolated tumour cells, micro- or macrometastases) in 696 patients (24.7%). Among patients with ALND and complete data to calculate combined risk (n=504), 67 and 437 patients had low and high combined risk, respectively. Patients at low risk had less ALND (47%) compared to patients at high risk (P<0.001). This study did not meet its primary objective because the FRR in patients with low risk was 16.4% (11 out of 67) (95% confidence interval (CI): 9.7-23.1%). In the high-risk group, 33.9% (148 out of 437) (95% CI: 29.6-38.4%) had non-SN metastases (P=0.004). In this controlled prospective study, metastatic SN patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 failed to identify patients at low risk of metastatic non-SN when completion ALND was not systematic.

  20. Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC)

    PubMed Central

    Shapiro, Lauren Q.; Sherman, Eric J.; Riaz, Nadeem; Setton, Jeremy; Koutcher, Lawrence; Zhang, Zhigang; Shi, Weiji; Fury, Matthew G.; Wolden, Suzanne L.; Pfister, David G.; Morris, Luc; Lee, Nancy

    2016-01-01

    Summary Objectives We previously reported inferior outcomes for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients treated with concurrent cetuximab vs. high-dose cisplatin with intensity-modulated radiation therapy (IMRT). Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin eligible patients at our institution received 5-fluorouracil (5FU)/carboplatin. We sought to compare concurrent cetuximab vs. 5FU/carboplatin vs. high-dose cisplatin with IMRT for LAHNSCC. Materials and methods Retrospective review was performed for LAHNSCC patients treated at Memorial Sloan-Kettering Cancer Center from 11/02 to 04/08 with concurrent cetuximab (n = 49), 5FU/carboplatin (n = 52), or cisplatin (n = 259) and IMRT. Overall survival (OS), locoregional failure (LRF), distant metastasis-free survival, and late toxicity were analyzed using univariate and multivariate analyses. OS analysis was confirmed by propensity score adjustment. Results Treatment groups were similar with regard to primary tumor site, overall stage, and alcohol and tobacco history. Cetuximab and 5FU/carboplatin patients were older, with lower performance status, more comorbidities, higher T classification, and worse renal function. On multivariate analysis, compared with cisplatin and 5FU/carboplatin, cetuximab was associated with inferior 4-year OS (86.9% vs. 70.2% vs. 40.9%; P < .0001) and 4-year LRF (6.3% vs. 9.7% vs. 40.2%; P < .0001). Late toxicity was highest with 5FU/carboplatin (25.0%) vs. cisplatin (8.0%) vs. cetuximab (7.7%). Conclusions Although 5FU/carboplatin patients were sicker and experienced greater toxicity than cisplatin patients, no significant difference was found in all endpoints. In contrast, despite similar pretreatment characteristics, outcomes for cetuximab vs. 5FU/carboplatin were significantly worse. We feel that caution should be used with routine use of cetuximab in the management of LAHNSCC. PMID:25132089

  1. Commentary on: "Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial." Rini BI, Bellmunt J, Clancy J, Wang K, Niethammer AG, Hariharan S, Escudier B. Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Joaquim Bellmunt, University Hospital del Mar-IMIM, Barcelona, Spain; Jill Clancy, Kongming Wang, Andreas G. Niethammer, Subramanian Hariharan, Pfizer, New York, NY; and Bernard Escudier, Institut Gustave Roussy, Villejuif, France.: J Clin Oncol. 2014 Mar 10;32(8):752-9; doi: 10.1200/JCO.2013.50.5305. [Epub 2013 Dec 2].

    PubMed

    Trump, Donald

    2016-05-01

    To prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC). In a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25mg intravenously, weekly) or IFN (9MIU subcutaneously thrice weekly) with bevacizumab (10mg/kg intravenously, every 2weeks). The primary end point was independently assessed progression-free survival (PFS). Median PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR] = 1.1; 95% CI: 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR = 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI)-15 and FKSI Disease-Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade≥3 adverse events more common (P<.001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2. Temsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Progress and challenges in psychosocial and behavioral research in cancer in the twentieth century.

    PubMed

    Holland, J C

    1991-02-01

    Research in the psychosocial and behavioral aspects of cancer has shown steady growth since the 1950s, and its course of development has paralleled the history of medical techniques in treating cancer. Table 1 outlines this parallel evolution from the 1850s to the 1960s. The roles of the American Cancer Society and the National Cancer Institute (NCI) in spearheading and nurturing research in this area are documented. Interest in psychooncologic questions can be traced back for centuries to the search for etiologic factors and psychologic variables that would explain individual vulnerability to cancer. The first psychologic studies of cancer patients were reported in 1951 and 1952 from the Massachusetts General Hospital and Memorial Sloan-Kettering Cancer Center, respectively. The 1970s saw new interest in psychosocial and behavioral research with many issues being addressed for the first time: better care of the terminally ill through more humanistic approaches including better means of pain control; ethical concerns related to patient rights and their status as subjects in experimental protocols; trying to measure quality of life for cancer patients on protocols; seeing the need for multidisciplinary collaborative groups to make up for the absence of formal training in this area; and the need to design valid, accurate measuring scales specific to the symptomology of patients with cancer. Table 4 outlines how the 1980s gave increasing recognition and support to the psychosocial dimensions of cancer. This period produced a series of key conferences that examined a broad research and education perspective and produced recommendations that remain a benchmark in regard to instrumentation, conceptual models, pitfalls of psychosocial research, training, and education, and the organization of research efforts. New precision has been added to the field in the past 6 years: studies measuring concurrent psychologic, endocrine, and immune function; use of statistical modeling

  3. Targeted therapy in renal cancer

    PubMed Central

    Dorff, Tanya B.; Goldkorn, Amir; Quinn, David I.

    2009-01-01

    Renal cell cancer (RCC) has an increasing incidence internationally and is a disease for which there have been limited therapeutic options until recently. The last decade has seen a vastly improved understanding of the biological and clinical factors that predict the outcome of this disease. We now understand some of the different molecular underpinnings of renal clear cell carcinoma by mutation or silencing of the von Hippel Lindau (VHL) gene and subsequent deregulated proliferation and angiogenesis. Survival in advanced disease is predicted by factors (performance status, anemia, hypercalcemia, and serum lactate dehydrogenase, time from diagnosis to recurrence) incorporated into the Memorial Sloan Kettering Cancer Center (MSKCC) criteria (also referred to as ‘Motzer’ criteria). These criteria allow classification of patients with RCC into good, intermediate and poor risk categories with median overall survivals of 22 months, 12 months and 5.4 months, respectively. Predicated upon these advances, six new targeted drugs (sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab and pazopanib) have been tested in well-designed phase III trials, selected or stratified for MSKCC risk criteria, with positive results. All of these new drugs act at least in part through vascular endothelial growth factor (VEGF) mediated pathways with other potential therapeutic impact on platelet-derived growth factor (PDGF), raf kinase and mammalian target of rapamycin (mTOR) pathways. Importantly, data from each of these trials show a consistent doubling of progression-free survival (PFS) over prior standard of care treatments. In addition, sorafenib, sunitinib and temsirolimus, have demonstrated significant overall survival (OS) benefits as well; further follow-up is required to determine whether the disease control exhibited by everolimus and pazopanib will translate into a survival advantage. These drugs are generally well tolerated, as demonstrated by quality

  4. SU-E-J-115: Using Markov Chain Modeling to Elucidate Patterns in Breast Cancer Metastasis Over Time and Space

    SciTech Connect

    Comen, E; Mason, J; Kuhn, P; Nieva, J; Newton, P; Norton, L; Venkatappa, N; Jochelson, M

    2014-06-01

    Purpose: Traditionally, breast cancer metastasis is described as a process wherein cancer cells spread from the breast to multiple organ systems via hematogenous and lymphatic routes. Mapping organ specific patterns of cancer spread over time is essential to understanding metastatic progression. In order to better predict sites of metastases, here we demonstrate modeling of the patterned migration of metastasis. Methods: We reviewed the clinical history of 453 breast cancer patients from Memorial Sloan Kettering Cancer Center who were non-metastatic at diagnosis but developed metastasis over time. We used the variables of organ site of metastases as well as time to create a Markov chain model of metastasis. We illustrate the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites. Results: Based on the clinical histories of 453 breast cancer patients who developed metastasis, we have learned (i) how to create the Markov transition matrix governing the probabilities of cancer progression from site to site; (ii) how to create a systemic network diagram governing disease progression modeled as a random walk on a directed graph; (iii) how to classify metastatic sites as ‘sponges’ that tend to only receive cancer cells or ‘spreaders’ that receive and release them; (iv) how to model the time-scales of disease progression as a Weibull probability distribution function; (v) how to perform Monte Carlo simulations of disease progression; and (vi) how to interpret disease progression as an entropy-increasing stochastic process. Conclusion: Based on our modeling, metastatic spread may follow predictable pathways. Mapping metastasis not simply by organ site, but by function as either a ‘spreader’ or ‘sponge’ fundamentally reframes our understanding of metastatic processes. This model serves as a novel platform from which we may integrate the evolving genomic landscape that drives cancer

  5. An open trial of aripiprazole for the treatment of delirium in hospitalized cancer patients.

    PubMed

    Boettger, Soenke; Breitbart, William

    2011-12-01

    The purpose of this study was to examine the efficacy and safety of aripiprazole in the treatment of delirium in hospitalized cancer patients, and to examine differential responses based on delirium subtypes. We conducted an analysis of 21 hospitalized cancer patients at Memorial Sloan-Kettering Cancer Center (MSKCC) who had been evaluated and treated for delirium with aripiprazole, using an MSKCC Institutional Review Board (IRB) approved Clinical Delirium Database. Measures used were the Memorial Delirium Assessment Scale (MDAS), the Karnofsky Scale of Performance Status (KPS), and side effect rating at baseline (T1), 2-3 days (T2), and 4-7 days (T3). All measurements were integrated into the routine clinical care of patients. Doses of aripiprazole were adjusted based on clinical response. Patients treated for delirium with aripiprazole experienced significant improvement and resolution of delirium, with MDAS scores declining from a mean of 18.0 at baseline (T1) to mean of 10.8 at T2 and a mean of 8.3 at T3. KPS scores improved from 28.1 at baseline (T1) to 35.2 at T2 and 41 at T3. Delirium resolved (based on MDAS < 10) in 52.4% of cases at T2 and in 76.2% at T3. The mean dosage of aripiprazole required was 18.3 mg (range of 5-30) daily at T3. In our cohort of patients with hypoactive delirium, we observed a delirium resolution rate of 100% compared to the cohort of patients with hyperactive delirium (58.3% rate of delirium resolution). MDAS scores improved from 15.6 at T1 to 5.7 at T3 in hypoactive delirium and from 19.9 at T1 to 10.2 at T3 in hyperactive delirium. In patients with pre-morbid cognitive deficits and the hyperactive subtype of delirium, we observed a more limited treatment response to aripiprazole treatment for delirium. There were no clinically significant side effects noted. Aripiprazole is effective and safe in the treatment of delirium in hospitalized cancer patients. These preliminary finding suggest that aripiprazole may be most effective in

  6. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers

    PubMed Central

    Ibrahimpasic, Tihana; Boucai, Laura; Shah, Ronak H.; Dogan, Snjezana; Ricarte-Filho, Julio C.; Krishnamoorthy, Gnana P.; Schultz, Nikolaus; Berger, Michael F.; Sander, Chris; Taylor, Barry S.; Ghossein, Ronald; Ganly, Ian; Fagin, James A.

    2016-01-01

    Foundation; the Society of Memorial Sloan Kettering; the Byrne fund; and Cycle for Survival. PMID:26878173

  7. TRASH TO TREASURE: CONVERTING COLD WAR LEGACY WASTE INTO WEAPONS AGAINST CANCER

    SciTech Connect

    Nicholas, R.G.; Lacy, N.H.; Butz, T.R.; Brandon, N.E.

    2004-10-06

    As part of its commitment to clean up Cold War legacy sites, the U.S. Department of Energy (DOE) has initiated an exciting and unique project to dispose of its inventory of uranium-233 (233U) stored at Oak Ridge National Laboratory (ORNL), and extract isotopes that show great promise in the treatment of deadly cancers. In addition to increasing the supply of potentially useful medical isotopes, the project will rid DOE of a nuclear concern and cut surveillance and security costs. For more than 30 years, DOE's ORNL has stored over 1,200 containers of fissile 233U, originally produced for several defense-related projects, including a pilot study that looked at using 233U as a commercial reactor fuel. This uranium, designated as special nuclear material, requires expensive security, safety, and environmental controls. It has been stored at an ORNL facility, Building 3019A, that dates back to the Manhattan Project. Down-blending the material to a safer form, rather than continuing to store it, will eliminate a $15 million a year financial liability for the DOE and increase the supply of medical isotopes by 5,700 percent. During the down-blending process, thorium-229 (229Th) will be extracted. The thorium will then be used to extract actinium-225 (225Ac), which will ultimately supply its progeny, bismuth-213 (213Bi), for on-going cancer research. The research includes Phase II clinical trials for the treatment of acute myelogenous leukemia at Sloan-Kettering Memorial Cancer Center in New York, as well as other serious cancers of the lungs, pancreas, and kidneys using a technique known as alpha-particle radioimmunotherapy. Alpha-particle radioimmunotherapy is based on the emission of alpha particles by radionuclides. 213Bi is attached to a monoclonal antibody that targets specific cells. The bismuth then delivers a high-powered but short-range radiation dose, effectively killing the cancerous cells but sparing the surrounding tissue. Production of the actinium and

  8. Targeting Signaling to YAP for the Therapy of NF2

    DTIC Science & Technology

    2016-12-01

    Ph.D. CONTRACTING ORGANIZATION: Memorial Sloan Kettering Cancer Center New York, NY 10065 REPORT DATE: December 2016 TYPE OF REPORT: FINAL PREPARED...Avenue New York, NY 10065-6007 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical...for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goals of this project are to utilize our new knowledge of the

  9. Poorly differentiated (anaplastic) seminoma of the testis.

    PubMed

    Cockburn, A G; Vugrin, D; Batata, M; Hajdu, S; Whitmore, W F

    1984-05-01

    Anaplastic seminoma constitutes approximately 17% of total experience with seminoma at Memorial Sloan-Kettering Cancer Center. Among 25 previously untreated patients, 11 (44%) were clinical Stage I, and 14 (56%) were clinical Stage II or III. Treatment of these 25 patients with the same regimens employed for classical seminoma yielded an overall 80% 5-year apparent cure rate. Survival rates were poor in eight previously treated patients referred with recurrence.

  10. What is the gold standard for comprehensive interinstitutional communication of perioperative information for thyroid cancer patients? A comparison of existing electronic health records with the current American Thyroid Association recommendations.

    PubMed

    Dos Reis, Laura L; Tuttle, R Michael; Alon, Eran; Bergman, Donald A; Bernet, Victor; Brett, Elise M; Cobin, Rhoda; Doherty, Gerard; Harris, Jeffrey R; Klopper, Joshua; Lee, Stephanie L; Lupo, Mark; Milas, Mira; Machac, Josef; Mechanick, Jeffrey I; Orloff, Lisa; Randolph, Gregory; Ross, Douglas S; Smallridge, Robert C; Terris, David James; Tufano, Ralph P; Mehra, Saral; Scherl, Sophie; Clain, Jason B; Urken, Mark L

    2014-10-01

    Appropriate management of well-differentiated thyroid cancer requires treating clinicians to have access to critical elements of the patient's presentation, surgical management, postoperative course, and pathologic assessment. Electronic health records (EHRs) provide an effective method for the storage and transmission of patient information, although most commercially available EHRs are not intended to be disease-specific. In addition, there are significant challenges for the sharing of relevant clinical information when providers involved in the care of a patient with thyroid cancer are not connected by a common EHR. In 2012, the American Thyroid Association (ATA) defined the critical elements for optimal interclinician communication in a position paper entitled, "The Essential Elements of Interdisciplinary Communication of Perioperative Information for Patients Undergoing Thyroid Cancer Surgery." We present a field-by-field comparison of the ATA's essential elements as applied to three contemporary electronic reporting systems: the Thyroid Surgery e-Form from Memorial Sloan-Kettering Cancer Center (MSKCC), the Alberta WebSMR from the University of Calgary, and the Thyroid Cancer Care Collaborative (TCCC). The MSKCC e-form fulfills 21 of 32 intraoperative fields and includes an additional 14 fields not specifically mentioned in the ATA's report. The Alberta WebSMR fulfills 45 of 82 preoperative and intraoperative fields outlined by the ATA and includes 13 additional fields. The TCCC fulfills 117 of 120 fields outlined by the ATA and includes 23 additional fields. Effective management of thyroid cancer is a highly collaborative, multidisciplinary effort. The patient information that factors into clinical decisions about thyroid cancer is complex. For these reasons, EHRs are particularly favorable for the management of patients with thyroid cancer. The MSKCC Thyroid Surgery e-Form, the Alberta WebSMR, and the TCCC each meet all of the general recommendations for

  11. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    SciTech Connect

    Katz, Matthew S.; Minsky, Bruce D. . E-mail: minskyb@mskcc.org; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-08-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  12. Evaluation of the Probability of Non-sentinel Lymph Node Metastasis in Breast Cancer Patients with Sentinel Lymph Node Metastasis using Two Different Methods

    PubMed Central

    Başoğlu, İrfan; Çelik, Muhammet Ferhat; Dural, Ahmet Cem; Ünsal, Mustafa Gökhan; Akarsu, Cevher; Baytekin, Halil Fırat; Kapan, Selin; Alış, Halil

    2015-01-01

    Objective The aim of this retrospective clinical study was to evaluate the accuracy and feasibility of two different clinical scales, namely the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Tenon’s axillary scoring system, which were developed for predicting the non-sentinel lymph node (NSLN) status in our breast cancer patients. Material and Methods The medical records of patients who were diagnosed with breast cancer between January 2010 and November 2013 were reviewed. Those who underwent sentinel lymph node biopsy (SLNB) for axillary staging were recruited for the study, and patients who were found to have positive SLNB and thus were subsequently subjected to axillary lymph node dissection (ALND) were also included. Patients who had neoadjuvant therapy, who had clinically positive axilla, and who had stage 4 disease were excluded. Patients were divided into two groups. Group 1 included those who had negative NSLNs, whereas Group 2 included those who had positive NSLNs. The following data were collected: age, tumor size, histopathological characteristics of the tumor, presence of lymphovascular invasion, presence of multifocality, number of negative and positive NSLNs, size of metastases, histopathological method used to define metastases, and receptor status of the tumor. The score of each patient was calculated according to the MSKCC nomogram and Tenon’s axillary scoring system. Statistical analysis was conducted to investigate the correlation between the scores and the involvement of NSLNs. Results The medical records of patients who were diagnosed with breast cancer and found to have SLNB for axillary staging was reviewed. Finally, 50 patients who had positive SLNB and thus were subsequently subjected to ALND were included in the study. There were 17 and 33 patients in Groups 1 and 2, respectively. Both the MSKCC nomogram and Tenon’s axillary scoring system were demonstrated to be significantly accurate in the prediction of the

  13. Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

    PubMed

    Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

    2017-02-01

    Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI. Of 118 patients with hematologic malignancies who had AMI, 58 (49%) had sTP. Twenty-five patients (43%) with sTP received aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p = .0001) and thienopyridine treatment (27% vs. 3%; p = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count < 50,000 cells/µL), guideline-recommended medical therapy is often withheld because of the fear of major bleeding. In this study, aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © Alpha

  14. Brachytherapy as part of the definitive management of squamous cancer of the base of tongue

    SciTech Connect

    Harrison, L.B.; Sessions, R.B.; Strong, E.W.; Fass, D.E.; Nori, D.; Fuks, Z. )

    1989-12-01

    Between 1981 and 1986, 17 patients were treated at the Department of Radiation Oncology at the Memorial Sloan-Kettering Cancer Center with squamous cancer of the base of the tongue whose definitive treatment included brachytherapy. There were four patients with T1 lesions, six with T2, six with T3, and one with T4. In general, treatment consisted of 5000-5400 cGy with external beam radiation and 2000-3000 cGy boost to the base of tongue via an Ir-192 implant using afterloading catheters. Necks were managed with elective radiation alone in the N0 group (n = 5) or with radiation plus neck dissection in the N+ group (n = 12). Five patients who would have required laryngectomy had they undergone primary surgery received neoadjuvant chemotherapy followed by external beam and implant as part of a larynx preservation study that was being done at our institution (4-T3, 1-T2). The range of follow-up is 8 to 59 months, with median follow-up of 24 months. No patients have been lost to follow-up. Crude local control by T-Stage are as follows: T1-4/4, T2-5/6, T3-5/6, T4-1/1. Actuarial local control at 24 months is 87%. There have been no neck failures. There have been five patients who had soft tissue ulceration (STU) and one patient who had osteoradionecrosis (ORN). All soft tissue ulceration patients have been successfully managed conservatively. The patient with osteoradionecrosis is currently being managed. In 4 of these 6 cases, the implant was the initial therapeutic intervention and the entire tumor bed was implanted. On the other hand, when external beam was the initial treatment, the boost was administered to the smaller volume of residual disease. Overall, 4 of 7 patients who had implant first developed either soft tissue ulceration or osteoradionecrosis, as opposed to 2 of 10 patients who had implant after external beam and/or chemotherapy.

  15. Overcoming intratumoural heterogeneity for reproducible molecular risk stratification: a case study in advanced kidney cancer.

    PubMed

    Lubbock, Alexander L R; Stewart, Grant D; O'Mahony, Fiach C; Laird, Alexander; Mullen, Peter; O'Donnell, Marie; Powles, Thomas; Harrison, David J; Overton, Ian M

    2017-06-26

    Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters. However, replication of results has proven challenging, and intratumoural heterogeneity (ITH) may confound attempts at tissue-based stratification. We investigated the influence of confounding ITH on the performance of a novel molecular prognostic model, enabled by pathologist-guided multiregion sampling (n = 183) of geographically separated mccRCC cohorts from the SuMR trial (development, n = 22) and the SCOTRRCC study (validation, n = 22). Tumour protein levels quantified by reverse phase protein array (RPPA) were investigated alongside clinical variables. Regularised wrapper selection identified features for Cox multivariate analysis with overall survival as the primary endpoint. The optimal subset of variables in the final stratification model consisted of N-cadherin, EPCAM, Age, mTOR (NEAT). Risk groups from NEAT had a markedly different prognosis in the validation cohort (log-rank p = 7.62 × 10(-7); hazard ratio (HR) 37.9, 95% confidence interval 4.1-353.8) and 2-year survival rates (accuracy = 82%, Matthews correlation coefficient = 0.62). Comparisons with established clinico-pathological scores suggest favourable performance for NEAT (Net reclassification improvement 7.1% vs International Metastatic Database Consortium score, 25.4% vs Memorial Sloan Kettering Cancer Center score). Limitations include the relatively small cohorts and associated wide confidence intervals on predictive performance. Our multiregion sampling approach enabled investigation of NEAT validation when limiting the number of samples analysed per tumour, which significantly degraded performance

  16. Use of Digitally Stained Multimodal Confocal Mosaic Images to Screen for Nonmelanoma Skin Cancer.

    PubMed

    Mu, Euphemia W; Lewin, Jesse M; Stevenson, Mary L; Meehan, Shane A; Carucci, John A; Gareau, Daniel S

    2016-12-01

    Confocal microscopy has the potential to provide rapid bedside pathologic analysis, but clinical adoption has been limited in part by the need for physician retraining to interpret grayscale images. Digitally stained confocal mosaics (DSCMs) mimic the colors of routine histologic specimens and may increase adaptability of this technology. To evaluate the accuracy and precision of 3 physicians using DSCMs before and after training to detect basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Mohs micrographic surgery fresh-tissue specimens. This retrospective study used 133 DSCMs from 64 Mohs tissue excisions, which included clear margins, residual BCC, or residual SCC. Discarded tissue from Mohs surgical excisions from the dermatologic surgery units at Memorial Sloan Kettering Cancer Center and Oregon Health & Science University were collected for confocal imaging from 2006 to 2011. Final data analysis and interpretation took place between 2014 and 2016. Two Mohs surgeons and a Mohs fellow, who were blinded to the correlating gold standard frozen section diagnoses, independently reviewed the DSCMs for residual nonmelanoma skin cancer (NMSC) before and after a brief training session (about 5 minutes). The 2 assessments were separated by a 6-month washout period. Diagnostic accuracy was characterized by sensitivity and specificity of detecting NMSC using DSCMs vs standard frozen histopathologic specimens. The diagnostic precision was calculated based on interobserver agreement and κ scores. Paired 2-sample t tests were used for comparative means analyses before and after training. The average respective sensitivities and specificities of detecting NMSC were 90% (95% CI, 89%-91%) and 79% (95% CI, 52%-100%) before training and 99% (95% CI, 99%-99%) (P = .001) and 93% (95% CI, 90%-96%) (P = .18) after training; for BCC, they were 83% (95% CI, 59%-100%) and 92% (95% CI, 81%-100%) before training and 98% (95% CI, 98%-98%) (P = .18) and 97% (95% CI

  17. TU-F-12A-01: Quantitative Non-Linear Compartment Modeling of 89Zr- and 124I- Labeled J591 Monoclonal Antibody Kinetics Using Serial Non-Invasive Positron Emission Tomography Imaging in a Pre-Clinical Human Prostate Cancer Mouse Model

    SciTech Connect

    Fung, EK; Cheal, SM; Chalasani, S; Fareedy, SB; Punzalan, B; Humm, JL; Osborne, JR; Larson, SM; Zanzonico, PB; Otto, B; Bander, NH

    2014-06-15

    -drug conjugates. Further exploration using the model will examine binding and radioisotope residence as antibody dose is increased to antigen saturation. The Center for Targeted Radioimmunotherapy and Theranostics, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center (MSK), NIH (R25-CA096945). Technical services provided by the MSK Small-Animal Imaging Core Facility were supported by the NIH (R24-CA83084, P30-CA08748, and P50-CA92629; Zanzonico). NCI, Center to Reduce Cancer Health Disparity (R21 CA153177-03; Osborne)

  18. Development and Internal Validation of a Novel Model to Identify the Candidates for Extended Pelvic Lymph Node Dissection in Prostate Cancer.

    PubMed

    Gandaglia, Giorgio; Fossati, Nicola; Zaffuto, Emanuele; Bandini, Marco; Dell'Oglio, Paolo; Bravi, Carlo Andrea; Fallara, Giuseppe; Pellegrino, Francesco; Nocera, Luigi; Karakiewicz, Pierre I; Tian, Zhe; Freschi, Massimo; Montironi, Rodolfo; Montorsi, Francesco; Briganti, Alberto

    2017-10-01

    Preoperative assessment of the risk of lymph node invasion (LNI) is mandatory to identify prostate cancer (PCa) patients who should receive an extended pelvic lymph node dissection (ePLND). To update a nomogram predicting LNI in contemporary PCa patients with detailed biopsy reports. Overall, 681 patients with detailed biopsy information, evaluated by a high-volume uropathologist, treated with radical prostatectomy and ePLND between 2011 and 2016 were identified. A multivariable logistic regression model predicting LNI was fitted and represented the basis for a coefficient-based nomogram. The model was evaluated using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs). The median number of nodes removed was 16. Overall, 79 (12%) patients had LNI. A multivariable model that included prostate-specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores with highest-grade PCa, and percentage of cores with lower-grade disease represented the basis for the nomogram. After cross validation, the predictive accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated improved risk prediction against threshold probabilities of LNI ≤20%. Using a cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven (1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs 89.5%), better calibration characteristics, and a higher net benefit at DCA. An ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. We developed a novel nomogram to predict lymph node invasion (LNI) in patients with clinically localized prostate cancer based on detailed biopsy reports. A lymph node dissection exclusively in men with a risk of LNI >7

  19. Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

    SciTech Connect

    Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.; Borst, Gerben R.; Rosenzweig, Kenneth E.; Lebesque, Joos V.; Jackson, Andrew

    2013-01-01

    Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD was calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.

  20. Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer.

    PubMed

    Scher, Howard I; Graf, Ryon P; Schreiber, Nicole A; McLaughlin, Brigit; Lu, David; Louw, Jessica; Danila, Daniel C; Dugan, Lyndsey; Johnson, Ann; Heller, Glenn; Fleisher, Martin; Dittamore, Ryan

    2017-06-01

    Circulating tumor cells (CTCs) expressing AR-V7 protein localized to the nucleus (nuclear-specific) identify metastatic castration-resistant prostate cancer (mCRPC) patients with improved overall survival (OS) on taxane therapy relative to the androgen receptor signaling inhibitors (ARSi) abiraterone acetate, enzalutamide, and apalutamide. To evaluate if expanding the positivity criteria to include both nuclear and cytoplasmic AR-V7 localization ("nuclear-agnostic") identifies more patients who would benefit from a taxane over an ARSi. The study used a cross-sectional cohort. Between December 2012 and March 2015, 193 pretherapy blood samples, 191 of which were evaluable, were collected and processed from 161 unique mCRPC patients before starting a new line of systemic therapy for disease progression at the Memorial Sloan Kettering Cancer Center. The association between two AR-V7 scoring criteria, post-therapy prostate-specific antigen (PSA) change (PTPC) and OS following ARSi or taxane treatment, was explored. One criterion required nuclear-specific AR-V7 localization, and the other required an AR-V7 signal but was agnostic to protein localization in CTCs. Correlation of AR-V7 status to PTPC and OS was investigated. Relationships with survival were analyzed using multivariable Cox regression and log-rank analyses. A total of 34 (18%) samples were AR-V7-positive using nuclear-specific criteria, and 56 (29%) were AR-V7-positive using nuclear-agnostic criteria. Following ARSi treatment, none of the 16 nuclear-specific AR-V7-positive samples and six of the 32 (19%) nuclear-agnostic AR-V7-positive samples had ≥50% PTPC at 12 weeks. The strongest baseline factor influencing OS was the interaction between the presence of nuclear-specific AR-V7-positive CTCs and treatment with a taxane (hazard ratio 0.24, 95% confidence interval 0.078-0.79; p=0.019). This interaction was not significant when nuclear-agnostic criteria were used. To reliably inform treatment selection

  1. New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients

    PubMed Central

    Kohrt, Holbrook E; Olshen, Richard A; Bermas, Honnie R; Goodson, William H; Wood, Douglas J; Henry, Solomon; Rouse, Robert V; Bailey, Lisa; Philben, Vicki J; Dirbas, Frederick M; Dunn, Jocelyn J; Johnson, Denise L; Wapnir, Irene L; Carlson, Robert W; Stockdale, Frank E; Hansen, Nora M; Jeffrey, Stefanie S

    2008-01-01

    Background Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model. Methods We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University. Results 285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic

  2. Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer.

    PubMed

    Scher, Howard I; Lu, David; Schreiber, Nicole A; Louw, Jessica; Graf, Ryon P; Vargas, Hebert A; Johnson, Ann; Jendrisak, Adam; Bambury, Richard; Danila, Daniel; McLaughlin, Brigit; Wahl, Justin; Greene, Stephanie B; Heller, Glenn; Marrinucci, Dena; Fleisher, Martin; Dittamore, Ryan

    2016-11-01

    A critical decision in the management of metastatic castration-resistant prostate cancer (mCRPC) is when to administer an androgen receptor signaling (ARS) inhibitor or a taxane. To determine if pretherapy nuclear androgen-receptor splice variant 7 (AR-V7) protein expression and localization on circulating tumor cells (CTCs) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes. For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center, 265 men with progressive mCRPC undergoing a change in treatment were considered; 86 were excluded because they were not initiating ARS or taxane therapy; and 18 were excluded for processing time constraints, leaving 161 patients for analysis. Between December 2012 and March 2015, blood was collected and processed from patients with progressive mCRPC immediately prior to new line of systemic therapy. Patients were followed up to 3 years. Prostate-specific antigen (PSA) response, time receiving therapy, radiographic progression-free survival (rPFS), and overall survival (OS). Overall, of 193 prospectively collected blood samples from 161 men with mCRPC, 191 were evaluable (128 pre-ARS inhibitor and 63 pretaxane). AR-V7-positive CTCs were found in 34 samples (18%), including 3% of first-line, 18% of second-line, and 31% of third- or greater line samples. Patients whose samples had AR-V7-positive CTCs before ARS inhibition had resistant posttherapy PSA changes (PTPC), shorter rPFS, shorter time on therapy, and shorter OS than those without AR-V7-positive CTCs. Overall, resistant PTPC were seen in 65 of 112 samples (58%) without detectable AR-V7-positive CTCs prior to ARS inhibition. There were statistically significant differences in OS but not in PTPC, time on therapy, or rPFS for patients with or without pretherapy AR-V7-positive CTCs treated with a taxane. A multivariable model adjusting for baseline factors associated with survival showed superior OS with taxanes relative

  3. The early diagnosis of lung cancer.

    PubMed

    Petty, T L

    2001-06-01

    Lung cancer is the most common fatal malignancy in both men and women, both in the United States and elsewhere in the world. Today, lung cancer is most often diagnosed on the basis of symptoms of advanced disease or when chest x-rays are taken for a variety of purposes unrelated to lung cancer detection. Unfortunately, in the United States no society or governmental agency recommends screening, even for patients with high risks, such as smokers with airflow obstruction or people with occupational exposures, including asbestos. The origins of this negative attitude toward lung cancer screening are found in 3 studies sponsored by the National Cancer Institute in the mid-1970s and conducted at Johns Hopkins University School of Medicine, the Mayo Clinic, and the Memorial Sloan-Kettering Center. These studies concluded that early identification of lung cancer through chest x-rays and cytologic diagnosis of sputum did not alter disease-specific mortality. However, patients with earlier stage disease were found through screening, which resulted in a higher resectability rate and improved survival in the screening group compared with a control group of patients receiving ordinary care. Patients in the control group often received annual chest x-rays during the course of this study, which was the standard of care at the time. Thus no true nonscreening control group resulted. The patients at highest risk were not enrolled in this study. No specific amount of pack-years of smoking intensity was required. Only men were screened. The studies were inadequately powered to show an improvement in mortality rate of less than 50%. Ninety percent of lung cancer occurs in smokers. The prevalence of lung cancer is 4 to 6 times greater when smokers have airflow obstruction than with normal airflow, when all other background factors, including smoking history, occupational risk, and family history, are the same. Screening heavy smokers (ie, > or = 30 pack-years) with airflow obstruction

  4. Translational Bioinformatics and Clinical Research (Biomedical) Informatics.

    PubMed

    Sirintrapun, S Joseph; Zehir, Ahmet; Syed, Aijazuddin; Gao, JianJiong; Schultz, Nikolaus; Cheng, Donavan T

    2016-03-01

    Translational bioinformatics and clinical research (biomedical) informatics are the primary domains related to informatics activities that support translational research. Translational bioinformatics focuses on computational techniques in genetics, molecular biology, and systems biology. Clinical research (biomedical) informatics involves the use of informatics in discovery and management of new knowledge relating to health and disease. This article details 3 projects that are hybrid applications of translational bioinformatics and clinical research (biomedical) informatics: The Cancer Genome Atlas, the cBioPortal for Cancer Genomics, and the Memorial Sloan Kettering Cancer Center clinical variants and results database, all designed to facilitate insights into cancer biology and clinical/therapeutic correlations.

  5. A novel PACU design for noise reduction.

    PubMed

    Smykowski, Lenore

    2008-08-01

    As redesign and renovation of patient care units occur, health care providers are looking to the literature and finding evidence for the importance of lowering environmental stressors. In the PACU at Memorial Sloan Kettering Cancer Center, patients historically expressed dissatisfaction with excessive noise levels and frequently cited overhearing staff conversations as most troubling. Nurses found the noise stressful and wearing. When the time approached to design the new PACU, we took the opportunity to explore a unique floor plan to minimize noise and improve privacy.

  6. Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy

    PubMed Central

    He, Yingna; Zhang, Linhua; Zhu, Dunwan; Song, Cunxian

    2014-01-01

    Tumor-targeting multifunctional liposomes simultaneously loaded with magnetic iron oxide nanoparticles (MIONs) as a magnetic resonance imaging (MRI) contrast agent and anticancer drug, mitoxantrone (Mit), were developed for targeted cancer therapy and ultrasensitive MRI. The gonadorelin-functionalized MION/Mit-loaded liposome (Mit-GML) showed significantly increased uptake in luteinizing hormone–releasing hormone (LHRH) receptor overexpressing MCF-7 (Michigan Cancer Foundation-7) breast cancer cells over a gonadorelin-free MION/Mit-loaded liposome (Mit-ML) control, as well as in an LHRH receptor low-expressing Sloan-Kettering HER2 3+ Ovarian Cancer (SK-OV-3) cell control, thereby leading to high cytotoxicity against the MCF-7 human breast tumor cell line. The Mit-GML formulation was more effective and less toxic than equimolar doses of free Mit or Mit-ML in the treatment of LHRH receptors overexpressing MCF-7 breast cancer xenografts in mice. Furthermore, the Mit-GML demonstrated much higher T2 enhancement than did Mit-ML controls in vivo. Collectively, the study indicates that the integrated diagnostic and therapeutic design of Mit-GML nanomedicine potentially allows for the image-guided, target-specific treatment of cancer. PMID:25187709

  7. Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy.

    PubMed

    He, Yingna; Zhang, Linhua; Zhu, Dunwan; Song, Cunxian

    2014-01-01

    Tumor-targeting multifunctional liposomes simultaneously loaded with magnetic iron oxide nanoparticles (MIONs) as a magnetic resonance imaging (MRI) contrast agent and anticancer drug, mitoxantrone (Mit), were developed for targeted cancer therapy and ultrasensitive MRI. The gonadorelin-functionalized MION/Mit-loaded liposome (Mit-GML) showed significantly increased uptake in luteinizing hormone-releasing hormone (LHRH) receptor overexpressing MCF-7 (Michigan Cancer Foundation-7) breast cancer cells over a gonadorelin-free MION/Mit-loaded liposome (Mit-ML) control, as well as in an LHRH receptor low-expressing Sloan-Kettering HER2 3+ Ovarian Cancer (SK-OV-3) cell control, thereby leading to high cytotoxicity against the MCF-7 human breast tumor cell line. The Mit-GML formulation was more effective and less toxic than equimolar doses of free Mit or Mit-ML in the treatment of LHRH receptors overexpressing MCF-7 breast cancer xenografts in mice. Furthermore, the Mit-GML demonstrated much higher T2 enhancement than did Mit-ML controls in vivo. Collectively, the study indicates that the integrated diagnostic and therapeutic design of Mit-GML nanomedicine potentially allows for the image-guided, target-specific treatment of cancer.

  8. Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism.

    PubMed

    Ertel, Adam; Tsirigos, Aristotelis; Whitaker-Menezes, Diana; Birbe, Ruth C; Pavlides, Stephanos; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2012-01-15

    Aging drives large systemic reductions in oxidative mitochondrial function, shifting the entire body metabolically towards aerobic glycolysis, a.k.a, the Warburg effect. Aging is also one of the most significant risk factors for the development of human cancers, including breast tumors. How are these two findings connected? One simplistic idea is that cancer cells rebel against the aging process by increasing their capacity for oxidative mitochondrial metabolism (OXPHOS). Then, local and systemic aerobic glycolysis in the aging host would provide energy-rich mitochondrial fuels (such as L-lactate and ketones) to directly "fuel" tumor cell growth and metastasis. This would establish a type of parasite-host relationship or "two-compartment tumor metabolism", with glycolytic/oxidative metabolic-coupling. The cancer cells ("the seeds") would flourish in this nutrient-rich microenvironment ("the soil"), which has been fertilized by host aging. In this scenario, cancer cells are only trying to save themselves from the consequences of aging, by engineering a metabolic mutiny, through the amplification of mitochondrial metabolism. We discuss the recent findings of Drs. Ron DePinho (MD Anderson) and Craig Thomspson (Sloan-Kettering) that are also consistent with this new hypothesis, linking cancer progression with metabolic aging. Using data mining and bioinformatics approaches, we also provide key evidence of a role for PGC1a/NRF1 signaling in the pathogenesis of (1) two-compartment tumor metabolism, and (2) mitochondrial biogenesis in human breast cancer cells.

  9. WE-A-207-01: Memorial Lecturer

    SciTech Connect

    Muller-Runkel, R

    2015-06-15

    The Medical Physics community lost one of its early pioneers in radiation oncology physics, Jacques Ovadia, who passed away in April of 2014 at the age of 90. Jacques received his Ph.D. in Nuclear Physics from the University of Illinois at Urbana in 1951. Subsequently, under the guidance of John Laughlin, he was introduced to the field of Medical Physics. When John moved to Memorial Sloan Kettering, Jacques followed him. There he gained clinical experience and expertise in the then cutting-edge field of high energy electron beam therapy. In 1956, Jacques joined Dr. Erich Uhlmann at Michael Reese Hospital in Chicago where one of the country’s first high energy medical linear accelerators had just been installed. During his 35 year tenure, Dr. Ovadia built a strong Medical Physics department that merged in 1984 with that of the University of Chicago. Jacques pioneered the use of high energy electron beams to treat deep seated tumors, multiple-field chest wall irradiation with variable electron energies, and even anticipated the current interest in high energy electron beam grid-therapy. At an early stage, he introduced a simulator, computerized treatment planning and in-house developed record and verify software. He retired in 1990 as Professor emeritus in Radiation and Cellular Biology at the University of Chicago. Dr. Ovadia was an early and strong supporter of AAPM. He was present at the Chicago ROMPS meeting where the decision was made to form an independent professional society for medical physics. He served as AAPM president in 1976. Jacques Ovadia is survived by his wife of 58 years, Florence, their daughter Corinne Graefe and son Marc Ovadia, MD, as well as four grandchildren and one great-grandchild. Jacques’ dynamic and ever enthusiastic personality inspired all who collaborated with him. He will be greatly missed.

  10. Evolving technologies drive the new roles of Biomedical Engineering.

    PubMed

    Frisch, P H; St Germain, J; Lui, W

    2008-01-01

    Rapidly changing technology coupled with the financial impact of organized health care, has required hospital Biomedical Engineering organizations to augment their traditional operational and business models to increase their role in developing enhanced clinical applications utilizing new and evolving technologies. The deployment of these technology based applications has required Biomedical Engineering organizations to re-organize to optimize the manner in which they provide and manage services. Memorial Sloan-Kettering Cancer Center has implemented a strategy to explore evolving technologies integrating them into enhanced clinical applications while optimally utilizing the expertise of the traditional Biomedical Engineering component (Clinical Engineering) to provide expanded support in technology / equipment management, device repair, preventive maintenance and integration with legacy clinical systems. Specifically, Biomedical Engineering is an integral component of the Medical Physics Department which provides comprehensive and integrated support to the Center in advanced physical, technical and engineering technology. This organizational structure emphasizes the integration and collaboration between a spectrum of technical expertise for clinical support and equipment management roles. The high cost of clinical equipment purchases coupled with the increasing cost of service has driven equipment management responsibilities to include significant business and financial aspects to provide a cost effective service model. This case study details the dynamics of these expanded roles, future initiatives and benefits for Biomedical Engineering and Memorial Sloan Kettering Cancer Center.

  11. African American women's breast memories, cancer beliefs, and screening behaviors.

    PubMed

    Thomas, Eileen C

    2004-01-01

    African American women experience higher breast cancer mortality and lower survival rates compared with white women of comparable age and cancer stage. The literature is lacking in studies that address the influence of past events on current health behaviors among women of diverse cultural groups. This qualitative exploratory study used participant narratives to examine associations between women's memories and feelings concerning their breasts and current breast cancer screening behaviors. Twelve professional African American women, aged 42 to 64 years, shared stories about memories and feelings regarding their breasts. Codes grouped together with related patterns and recurrences revealed categories that encompassed the language and culture of the participants. The categories identified were Seasons of Breast Awareness, Womanhood, Self-Portraits, Breast Cancer and Cancer Beliefs, Breast Cancer Screening Experiences, and Participants' Advice for Change. These categories provide direction for further exploration of barriers to health promotion practices among African American women and women in general.

  12. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome.

    PubMed

    Fagotti, Anna; Ferrandina, Gabriella; Vizzielli, Giuseppe; Fanfani, Francesco; Gallotta, Valerio; Chiantera, Vito; Costantini, Barbara; Margariti, Pasquale Alessandro; Gueli Alletti, Salvatore; Cosentino, Francesco; Tortorella, Lucia; Scambia, Giovanni

    2016-05-01

    To establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL). This is a single-Institution, superiority, randomised phase III trial enrolling supposed AEOC women. Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index (PI) of tumour load. All AEOC women with PI≥8 or≤12 (considered as HTL) were included. They were randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy (arm A, standard), or NACT followed by IDS (NACT/IDS) (arm B, experimental). Co-primary outcome measures were postoperative complications (graded according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system) and progression free survival (PFS); secondary outcomes were overall survival, and quality of life (QoL). QoL was assessed using the EORTC QoL questionnaires. A sample size of 110 patients was required for the analysis of the first co-primary end-point (major peri-operative morbidity) whereas recruitment is still on-going to achieve the statistical power on PFS. Between October 2011 and November 2014, we registered 280 AEOC. Of the 110 eligible women, 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery, rates of complete residual disease (residual tumour=0 cm) were superimposable between the groups (45.5% versus 57.7%; p=0.206). Twenty-nine patients (52.7%) in arm A experienced early grade III-IV complications versus three patients (5.7%) in IDS (p=0.0001). The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage (17/55 women (30.9%) in arm A versus 1/52 (1.9%) in arm B, p=0.0001). Three grade IV (5.4%) (i.e., two re-operations for postoperative

  13. Is cancer a metabolic rebellion against host aging?

    PubMed Central

    Ertel, Adam; Tsirigos, Aristotelis; Whitaker-Menezes, Diana; Birbe, Ruth C; Pavlides, Stephanos; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Howell, Anthony

    2012-01-01

    Aging drives large systemic reductions in oxidative mitochondrial function, shifting the entire body metabolically toward aerobic glycolysis, a.k.a, the Warburg effect. Aging is also one of the most significant risk factors for the development of human cancers, including breast tumors. How are these two findings connected? One simplistic idea is that cancer cells rebel against the aging process by increasing their capacity for oxidative mitochondrial metabolism (OXPHOS). Then, local and systemic aerobic glycolysis in the aging host would provide energy-rich mitochondrial fuels (such as L-lactate and ketones) to directly “fuel” tumor cell growth and metastasis. This would establish a type of parasite-host relationship or “two-compartment tumor metabolism,” with glycolytic/oxidative metabolic coupling. The cancer cells (“the seeds”) would flourish in this nutrient-rich microenvironment (“the soil”), which has been fertilized by host aging. In this scenario, cancer cells are only trying to save themselves from the consequences of aging by engineering a metabolic mutiny, through the amplification of mitochondrial metabolism. We discuss the recent findings of Drs. Ron DePinho (MD Anderson) and Craig Thomspson (Sloan-Kettering) that are also consistent with this new hypothesis, linking cancer progression with metabolic aging. Using data mining and bioinformatics approaches, we also provide key evidence of a role for PGC1a/NRF1 signaling in the pathogenesis of (1) two-compartment tumor metabolism and (2) mitochondrial biogenesis in human breast cancer cells. PMID:22234241

  14. A Prospective Study of Autobiographical Memory and Posttraumatic Stress Disorder Following Cancer

    ERIC Educational Resources Information Center

    Kangas, Maria; Henry, Jane L.; Bryant, Richard A.

    2005-01-01

    In this study, the authors investigated the relationship between autobiographical memory and the onset and maintenance of distressing memories following cancer. In Study 1, participants recently diagnosed with head, neck, or lung cancer were assessed for acute stress disorder (ASD). Participants with ASD reported fewer specific memories than did…

  15. A Prospective Study of Autobiographical Memory and Posttraumatic Stress Disorder Following Cancer

    ERIC Educational Resources Information Center

    Kangas, Maria; Henry, Jane L.; Bryant, Richard A.

    2005-01-01

    In this study, the authors investigated the relationship between autobiographical memory and the onset and maintenance of distressing memories following cancer. In Study 1, participants recently diagnosed with head, neck, or lung cancer were assessed for acute stress disorder (ASD). Participants with ASD reported fewer specific memories than did…

  16. Ski regulates Hippo and TAZ signaling to suppress breast cancer progression.

    PubMed

    Rashidian, Juliet; Le Scolan, Erwan; Ji, Xiaodan; Zhu, Qingwei; Mulvihill, Melinda M; Nomura, Daniel; Luo, Kunxin

    2015-02-10

    Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor-β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and subsequent degradation of TAZ. Ski also promoted the degradation of a constitutively active TAZ mutant that is not phosphorylated by Lats, suggesting the existence of a Lats2-independent degradation pathway. Finally, we showed that Ski repressed the transcriptional activity of TAZ by binding to the TAZ partner TEAD and recruiting the transcriptional co-repressor NCoR1 to the TEAD-TAZ complex. Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells.

  17. In situ vaccine, immunological memory and cancer cure.

    PubMed

    Tsung, Kangla; Norton, Jeffrey A

    2016-01-01

    As surgery is able to remove primary tumors and limit metastases, the major challenge in cancer management is the prevention of post-resection recurrence and metastases. From the immune point of view, tumor resection removes the supply of tumor antigens that maintain an active concomitant antitumor immunity elicited by the primary tumor, and may also signal for deposition of immunological memory against future metastases. However, the natural course of this antitumor immunity in many cancer patients following complete tumor resection may not be favorable because protection is often lost after 1-3 years. Recent studies suggest that chemotherapy is able to activate this pre-existing antitumor immunity, and tumor resection following immune activation may lead to higher levels of immunological memory against future tumor antigens (in the form of metastases). Interleukin-12 added to chemotherapy mimics the function of a vaccine adjuvant in that it helps to enhance the antitumor immunity activated by chemotherapy and leaves a much stronger antitumor immune memory. This finding, when applied to cancer management, may help to maintain a strong and long lasting antitumor immunity following complete tumor resection, thus eliminating post-surgery recurrence and metastases.

  18. Translational Bioinformatics and Clinical Research (Biomedical) Informatics.

    PubMed

    Sirintrapun, S Joseph; Zehir, Ahmet; Syed, Aijazuddin; Gao, JianJiong; Schultz, Nikolaus; Cheng, Donavan T

    2015-06-01

    Translational bioinformatics and clinical research (biomedical) informatics are the primary domains related to informatics activities that support translational research. Translational bioinformatics focuses on computational techniques in genetics, molecular biology, and systems biology. Clinical research (biomedical) informatics involves the use of informatics in discovery and management of new knowledge relating to health and disease. This article details 3 projects that are hybrid applications of translational bioinformatics and clinical research (biomedical) informatics: The Cancer Genome Atlas, the cBioPortal for Cancer Genomics, and the Memorial Sloan Kettering Cancer Center clinical variants and results database, all designed to facilitate insights into cancer biology and clinical/therapeutic correlations. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 125I implantation for carcinoma of prostate. Further follow-up of first 100 cases.

    PubMed

    Grossman, H B; Batata, M; Hilaris, B; Whitmore, W F

    1982-12-01

    Analysis of the first 100 patients at the Memorial Sloan-Kettering Cancer Center with Stage B or C prostatic cancer treated by pelvic lymph node dissection and Iodine-125 implantation and endocrine therapy when specifically indicated revealed five-year survival rates of 87 and 77 per cent, respectively. Tumor stage, tumor grade, and lymph node metastasis each correlated with survival, but the latter was the most significant factor. Although routine follow-up biopsies were not performed, local tumor control as judged by serial digital rectal examination defined a prognostically favored group of patients. In the absence of controls, however, whether the latter response indicates a salutary effect of the treatment which produces an improved survival or merely identifies a group of patients who were predetermined to have a more favorable survival is undetermined.

  20. Fabrication of a provisional nasal prosthesis.

    PubMed

    Rosen, Evan B; Golden, Marjorie; Huryn, Joseph M

    2014-11-01

    A technique for making a provisional nasal prosthesis for interim use after the ablation of a midface tumor is described. The technique is especially useful for the re-creation of a nasal form in an expedient and cost-effective manner. A preoperative definitive cast, or moulage, of the patient that includes a nasal form is used to fabricate a vacuum form of the midface. The vacuum form is evaluated on the patient, the extension is adjusted, and an external adhesive knit liner is applied to give the appearance of a contoured nasal bandage. The provisional nasal prosthesis is attached with medical adhesive tape and removed daily by the patient. The prosthesis is easily replaced during the course of treatment and has been found to be functional and esthetically acceptable to those patients receiving care from the Dental Service at Memorial Sloan Kettering Cancer Center.

  1. Bone sarcomas in Paget disease: a study of 85 patients

    SciTech Connect

    Smith, J.; Botet, J.F.; Yeh, S.D.J.

    1984-09-01

    This is a comprehensive review of 85 patients who had bone sarcoma associated with Paget disease and who were seen at Memorial Sloan-Kettering Cancer Center between 1927 and 1982. There was an almost equal distribution of tumors in the axial and the appendicular skeletons. The pelvis, humerus, femur, and skull were the tumor sites in 80% of cases. The tumors were bulky large soft tissue masses. Lytic lesions were more common than sclerotic lesions. Methylene diphosphonate scans of the bone often showed a cold area that was associated with marked increase in uptake on the gallium scan. Angiography, which was performed in 13 patients, was useful, but CT was much more helpful in showing the soft tissue mass as well as the extent of bony disease. Only three patients in this study survived for five years.

  2. Improved Yields of Iodine-124 from the Enriched Tellurium-124 Dioxide/Aluminum Oxide Target

    NASA Astrophysics Data System (ADS)

    Finn, R. D.; Qiao, J.; Nacca, A.; Sheh, Y.; Lom, C.; Balatoni, J.; Cai, S.; Bornmann, W.; Pentlow, K.

    2003-08-01

    The escalating clinical application of Positron Emission Tomography results from the novel radiotracers which are available to monitor specific biochemical or physiologic processes. Future developments of the technique will require an increasing availability of additional unique radioligands and radionuclides. Iodine-124, a radionuclide whose potential for both diagnostic and therapeutic applications is widely recognized, has been prepared at Memorial Sloan-Kettering Cancer Center on a weekly basis for several years (1). With its characteristic 4.18 day half life and complex decay scheme (2) which includes positron emission (22.0 ± 0.5%) and electron capture (78 ± 0.5%), this radionuclide has been shown to be appropriate for radiotracers describing slow physiologic processes with the clearance of non-specific radioactivity. The refinements and modifications being engineered into the cyclotron target system to increase the absolute yield of recoverable radioactivity from each irradiation and its chemical processing of the reusable solid target matrix are described..

  3. Cyclotron production and potential clinical application of Iodine-124 labeled radiotracers

    NASA Astrophysics Data System (ADS)

    Finn, R.; Balatoni, J.; Kothari, P.; Pentlow, K.; Sheh, Y.; Lom, C.; Dahl, J.; Eckelman, W.; Plascjak, P.; Adams, H. R.; Larson, S. M.

    2001-07-01

    Positron emission tomography (PET) is a dynamic molecular imaging technique applicable to clinical research, drug development as well as clinical diagnoses. The potential for PET is derived from specificity of the radiotracers and radioligands that are synthesized to monitor the biochemical or physiological processes. Further developments will depend on an increasing availability of unique radiotracers. Iodine-124, a radionuclide that has potential for both diagnostic and therapeutic applications, possesses a half-life of 4.18 days and decays by positron emission (23.3%) and electron capture (76.7%). The preparation of this radionuclide via the 124Te(p,n)124I nuclear reaction is described as well as chemistry associated with the preparation of specific radiotracers and radiopharmaceuticals incorporating iodine-124 at Memorial Sloan-Kettering Cancer Center.

  4. Electroplated targets for production of unique PET radionuclides

    NASA Astrophysics Data System (ADS)

    Bui, V.; Sheh, Y.; Finn, R.; Francesconi, L.; Cai, S.; Schlyer, D.; Wieland, B.

    1995-12-01

    The past decade has witnessed the applications of positron emission tomography (PET) evolving from a purely research endeavor to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in both medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules, i.e. monoclonal antibodies and peptides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center (MSKCC) cyclotron are examples of target design and development applicable to many medical accelerators.

  5. Production and quality assurance of cyclotron produced iodine-124 from enriched tellurium targets

    SciTech Connect

    Balatoni, J.; Finn, R.; Blasberg, R.; Tjuvajev, J.; Larson, S.

    1999-06-01

    The production of iodine-124 and the formulation of specific radiopharmaceuticals are an important component of the Positron Emission Tomography Program at Memorial Sloan-Kettering Cancer Center. Preparation of iodine-124 using the CS-15 cyclotron employing the (p, n) nuclear reaction on an enriched {sup 124}TeO{sub 2} solid target has been initiated. The radioiodine is isolated by a dry distillation technique from the target matrix. The mass and oxidation states of iodine species isolated from the processing were analyzed using high pressure liquid chromatography. Employing a C-8 reverse-phase column (1) and isocratic elution conditions, the chemical purity and specific activity of the various radioiodine species was determined. The method provides a routine means for evaluation of the purity of the radioiodide prior to and post radiolabeling essential for the efficient utilization and recovery of this important radionuclide. {copyright} {ital 1999 American Institute of Physics.}

  6. Production and quality assurance of cyclotron produced iodine-124 from enriched tellurium targets

    SciTech Connect

    Balatoni, J.; Finn, R.; Blasberg, R.; Tjuvajev, J.; Larson, S.

    1999-06-10

    The production of iodine-124 and the formulation of specific radiopharmaceuticals are an important component of the Positron Emission Tomography Program at Memorial Sloan-Kettering Cancer Center. Preparation of iodine-124 using the CS-15 cyclotron employing the (p, n) nuclear reaction on an enriched {sup 124}TeO{sub 2} solid target has been initiated. The radioiodine is isolated by a dry distillation technique from the target matrix. The mass and oxidation states of iodine species isolated from the processing were analyzed using high pressure liquid chromatography. Employing a C-8 reverse-phase column (1) and isocratic elution conditions, the chemical purity and specific activity of the various radioiodine species was determined. The method provides a routine means for evaluation of the purity of the radioiodide prior to and post radiolabeling essential for the efficient utilization and recovery of this important radionuclide.

  7. Electroplating targets for production of unique PET radionuclides

    SciTech Connect

    Bui, V.; Sheh, Y.; Finn, R.

    1994-12-31

    The past decade has witnessed the applications of Positron Emission Tomography (PET) evolving from a purely research endeavour to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules i.e. monoclonal antibodies and pepetides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center cyclotron are examples of target design and development applicable to many medical accelerators.

  8. Improved Yields of Iodine-124 from the Enriched Tellurium-124 Dioxide/Aluminum Oxide Target

    SciTech Connect

    Finn, R.D.; Qiao, J.; Nacca, A.; Sheh, Y.; Lom, C.; Balatoni, J.; Cai, S.; Bornmann, W.; Pentlow, K.

    2003-08-26

    The escalating clinical application of Positron Emission Tomography results from the novel radiotracers which are available to monitor specific biochemical or physiologic processes. Future developments of the technique will require an increasing availability of additional unique radioligands and radionuclides. Iodine-124, a radionuclide whose potential for both diagnostic and therapeutic applications is widely recognized, has been prepared at Memorial Sloan-Kettering Cancer Center on a weekly basis for several years (1). With its characteristic 4.18 day half life and complex decay scheme (2) which includes positron emission (22.0 {+-} 0.5%) and electron capture (78 {+-} 0.5%), this radionuclide has been shown to be appropriate for radiotracers describing slow physiologic processes with the clearance of non-specific radioactivity. The refinements and modifications being engineered into the cyclotron target system to increase the absolute yield of recoverable radioactivity from each irradiation and its chemical processing of the reusable solid target matrix are described.

  9. Production and quality assurance of cyclotron produced iodine-124 from enriched tellurium targets

    NASA Astrophysics Data System (ADS)

    Balatoni, J.; Finn, R.; Blasberg, R.; Tjuvajev, J.; Larson, S.

    1999-06-01

    The production of iodine-124 and the formulation of specific radiopharmaceuticals are an important component of the Positron Emission Tomography Program at Memorial Sloan-Kettering Cancer Center. Preparation of iodine-124 using the CS-15 cyclotron employing the (p, n) nuclear reaction on an enriched 124TeO2 solid target has been initiated. The radioiodine is isolated by a dry distillation technique from the target matrix. The mass and oxidation states of iodine species isolated from the processing were analyzed using high pressure liquid chromatography. Employing a C-8 reverse-phase column (1) and isocratic elution conditions, the chemical purity and specific activity of the various radioiodine species was determined. The method provides a routine means for evaluation of the purity of the radioiodide prior to and post radiolabeling essential for the efficient utilization and recovery of this important radionuclide.

  10. 75 FR 79381 - Determination of Regulatory Review Period for Purposes of Patent Extension; FOLOTYN

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Restoration Act of 1984 (Pub. L. 98-417) and the Generic Animal Drug and Patent Term Restoration Act (Pub. L... patented item (human drug product, animal drug product, medical device, food additive, or color additive.... Patent No. 6,028,071) from Southern Research Institute, Sloan-Kettering Institute for Cancer Research...

  11. Memory

    MedlinePlus

    ... it has to decide what is worth remembering. Memory is the process of storing and then remembering this information. There are different types of memory. Short-term memory stores information for a few ...

  12. Risk factors and classifications of hilar cholangiocarcinoma.

    PubMed

    Suarez-Munoz, Miguel Angel; Fernandez-Aguilar, Jose Luis; Sanchez-Perez, Belinda; Perez-Daga, Jose Antonio; Garcia-Albiach, Beatriz; Pulido-Roa, Ysabel; Marin-Camero, Naiara; Santoyo-Santoyo, Julio

    2013-07-15

    Cholangiocarcinoma is the second most common primary malignant tumor of the liver. Perihilar cholangiocarcinoma or Klatskin tumor represents more than 50% of all biliary tract cholangiocarcinomas. A wide range of risk factors have been identified among patients with Perihilar cholangiocarcinoma including advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, cholecystitis, parasitic infection (Opisthorchis viverrini and Clonorchis sinensis), inflammatory bowel disease, alcoholic cirrhosis, nonalcoholic cirrhosis, chronic pancreatitis and metabolic syndrome. Various classifications have been used to describe the pathologic and radiologic appearance of cholangiocarcinoma. The three systems most commonly used to evaluate Perihilar cholangiocarcinoma are the Bismuth-Corlette (BC) system, the Memorial Sloan-Kettering Cancer Center and the TNM classification. The BC classification provides preoperative assessment of local spread. The Memorial Sloan-Kettering cancer center proposes a staging system according to three factors related to local tumor extent: the location and extent of bile duct involvement, the presence or absence of portal venous invasion, and the presence or absence of hepatic lobar atrophy. The TNM classification, besides the usual descriptors, tumor, node and metastases, provides additional information concerning the possibility for the residual tumor (R) and the histological grade (G). Recently, in 2011, a new consensus classification for the Perihilar cholangiocarcinoma had been published. The consensus was organised by the European Hepato-Pancreato-Biliary Association which identified the need for a new staging system for this type of tumors. The classification includes information concerning biliary or vascular (portal or arterial) involvement, lymph node status or metastases, but also other essential aspects related to the surgical risk, such as remnant hepatic volume or the possibility of underlying disease.

  13. Memory.

    ERIC Educational Resources Information Center

    McKean, Kevin

    1983-01-01

    Discusses current research (including that involving amnesiacs and snails) into the nature of the memory process, differentiating between and providing examples of "fact" memory and "skill" memory. Suggests that three brain parts (thalamus, fornix, mammilary body) are involved in the memory process. (JN)

  14. Memory.

    ERIC Educational Resources Information Center

    McKean, Kevin

    1983-01-01

    Discusses current research (including that involving amnesiacs and snails) into the nature of the memory process, differentiating between and providing examples of "fact" memory and "skill" memory. Suggests that three brain parts (thalamus, fornix, mammilary body) are involved in the memory process. (JN)

  15. Integrative Cancer Care in a US Academic Cancer Centre: The Memorial Sloan–Kettering Experience

    PubMed Central

    Deng, G.

    2008-01-01

    Various surveys show that interest in complementary and alternative medicine (cam) is high among cancer patients. Patients want to explore all options that may help their treatment. Many cam modalities offer patients an active role in their self-care, and the resulting sense of empowerment is very appealing. On the other hand, many unscrupulous marketeers promote alternative cancer “cures,” targeting cancer patients who are particularly vulnerable. Some alternative therapies can hurt patients by delaying effective treatment or by causing adverse effects or detrimental interactions with other medications. It is not in the best interest of cancer patients if they cannot get appropriate guidance on the use of cam from the health care professionals who are part of their cancer care team. The Integrative Medicine Service at Memorial Sloan–Kettering Cancer Center in New York was established in 1999 to address patient interest in cam, to incorporate helpful complementary therapies into each patient’s overall treatment management, to guide patients in avoiding harmful alternative therapies, and to develop prospective research to evaluate the efficacy of cam modalities. PMID:18769574

  16. Learning and memory performance in a cohort of clinically referred breast cancer survivors: the role of attention versus forgetting in patient-reported memory complaints

    PubMed Central

    Root, James C.; Ryan, Elizabeth; Barnett, Gregory; Andreotti, Charissa; Bolutayo, Kemi; Ahles, Tim

    2015-01-01

    Objective While forgetfulness is widely reported by breast cancer survivors, studies documenting objective memory performance yield mixed, largely inconsistent, results. Failure to find consistent, objective memory issues may be due to the possibility that cancer survivors misattribute their experience of forgetfulness to primary memory issues rather than to difficulties in attention at the time of learning. Methods To clarify potential attention issues, factor scores for Attention Span, Learning Efficiency, Delayed Memory, and Inaccurate Memory were analyzed for the CVLT-II in 64 clinically-referred breast cancer survivors with self-reported cognitive complaints; item analysis was conducted to clarify specific contributors to observed effects and contrasts between learning and recall trials were compared to normative data. Performance on broader cognitive domains is also reported. Results The Attention Span factor, but not Learning Efficiency, Delayed Memory, or Inaccurate Memory factors, was significantly affected in this clinical sample. Contrasts between trials were consistent with normative data and did not indicate greater loss of information over time than in the normative sample. Conclusions Results of this analysis suggest attentional dysfunction may contribute to subjective and objective memory complaints in breast cancer survivors. These results are discussed in the context of broader cognitive effects following treatment for clinicians who may see cancer survivors for assessment. PMID:25044928

  17. Learning and memory performance in a cohort of clinically referred breast cancer survivors: the role of attention versus forgetting in patient-reported memory complaints.

    PubMed

    Root, James C; Ryan, Elizabeth; Barnett, Gregory; Andreotti, Charissa; Bolutayo, Kemi; Ahles, Tim

    2015-05-01

    While forgetfulness is widely reported by breast cancer survivors, studies documenting objective memory performance yield mixed, largely inconsistent, results. Failure to find consistent, objective memory issues may be due to the possibility that cancer survivors misattribute their experience of forgetfulness to primary memory issues rather than to difficulties in attention at the time of learning. To clarify potential attention issues, factor scores for Attention Span, Learning Efficiency, Delayed Memory, and Inaccurate Memory were analyzed for the California Verbal Learning Test-Second Edition (CVLT-II) in 64 clinically referred breast cancer survivors with self-reported cognitive complaints; item analysis was conducted to clarify specific contributors to observed effects, and contrasts between learning and recall trials were compared with normative data. Performance on broader cognitive domains is also reported. The Attention Span factor, but not Learning Efficiency, Delayed Memory, or Inaccurate Memory factors, was significantly affected in this clinical sample. Contrasts between trials were consistent with normative data and did not indicate greater loss of information over time than in the normative sample. Results of this analysis suggest that attentional dysfunction may contribute to subjective and objective memory complaints in breast cancer survivors. These results are discussed in the context of broader cognitive effects following treatment for clinicians who may see cancer survivors for assessment. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Verbal memory in breast cancer patients treated with chemotherapy with doxorubicin and cyclophosphamide.

    PubMed

    Andryszak, P; Wiłkość, M; Żurawski, B; Izdebski, P

    2017-08-29

    Memory is one of the crucial human cognitive functions, and deficits in memory processes may lead to difficulties in everyday functioning. The aim of this study was to analyse the effect of anthracycline-based adjuvant chemotherapy (AC) used in breast cancer treatment on verbal memory and learning. We also evaluated the relationship between verbal memory and psychological, somatic and socio-demographic factors. The study was carried out on a group of 31 women with early breast cancer treated with adjuvant chemotherapy and 30 healthy controls. The patients underwent neuropsychological assessment using the Rey Auditory Verbal Learning Test at three time points: before chemotherapy, mid-chemotherapy and post-chemotherapy. The examination in the controls was conducted at the same time intervals. We found an association between AC-schema chemotherapy and deficits in delayed memory. A deterioration in performance after treatment was observed in 19% of patients. The results showed no deterioration of immediate memory or the verbal learning process. Moreover, a positive relationship was shown between the level of education, physical fitness and the functioning of verbal memory. The results of the study also indicate that age and hormonal status are factors that may increase the possibility of deficits in verbal memory after AC-schema chemotherapy. © 2017 John Wiley & Sons Ltd.

  19. Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression

    PubMed Central

    Li, Wen; Gan, Chen; Lv, Yue; Wang, Shanghu; Cheng, Huaidong

    2017-01-01

    Abstract This study aimed to investigate prospective memory impairment in patients with breast cancer with different expression of hormone receptors, including the estrogen receptor (ER) and the progesterone receptor (PR). A total of 120 patients with breast cancer who underwent chemotherapy following surgery were divided into 2 groups. The A group included 60 patients with ER−/PR− status, and the B group included 60 patients with ER+/PR+ status. After 6 cycles of postoperative adjuvant chemotherapy, all patients were administered neuropsychological and prospective memory tests, such as the Mini-Mental State Examination (MMSE), verbal fluency test (VFT), and digit span test (DST), as well as examination of event-based prospective memory (EBPM) and time-based prospective memory (TBPM). As the neuropsychological background test results showed, there were no significant differences in MMSE, DST, and TBPM scores (∗:P > 0.05) between patients with breast cancer in the ER−/PR− and ER+/PR+ groups, while the VFT and EBPM scores were significantly greater in patients with breast cancer with ER+/PR+ status than in those with ER−/PR− status (∗∗: P < 0.01), indicating that patients with ER−/PR− status have significant impairment in EBPM, although not in TBPM. The results of the present study indicate that different hormone receptor expression in patients with breast cancer may be associated with heterogeneity of chemotherapy-induced prospective memory impairment. PMID:28353608

  20. Children's Memories for Painful Cancer Treatment Procedures: Implications for Distress.

    ERIC Educational Resources Information Center

    Chen, Edith; Zeltzer, Lonnie K.; Craske, Michelle G.; Katz, Ernest R.

    2000-01-01

    Examined memory of 3- to 18-year-olds with leukemia regarding lumbar punctures (LP). Found that children displayed considerable accuracy for event details, with accuracy increasing with age. Use of Versed (anxiolytic medication described as a "memory blocker") was not related to recall. Higher distress predicted greater exaggerations in…

  1. Children's Memories for Painful Cancer Treatment Procedures: Implications for Distress.

    ERIC Educational Resources Information Center

    Chen, Edith; Zeltzer, Lonnie K.; Craske, Michelle G.; Katz, Ernest R.

    2000-01-01

    Examined memory of 3- to 18-year-olds with leukemia regarding lumbar punctures (LP). Found that children displayed considerable accuracy for event details, with accuracy increasing with age. Use of Versed (anxiolytic medication described as a "memory blocker") was not related to recall. Higher distress predicted greater exaggerations in…

  2. YOCAS©® Yoga Reduces Self-reported Memory Difficulty in Cancer Survivors in a Nationwide Randomized Clinical Trial: Investigating Relationships Between Memory and Sleep.

    PubMed

    Janelsins, Michelle C; Peppone, Luke J; Heckler, Charles E; Kesler, Shelli R; Sprod, Lisa K; Atkins, James; Melnik, Marianne; Kamen, Charles; Giguere, Jeffrey; Messino, Michael J; Mohile, Supriya G; Mustian, Karen M

    2016-09-01

    Background Interventions are needed to alleviate memory difficulty in cancer survivors. We previously showed in a phase III randomized clinical trial that YOCAS©® yoga-a program that consists of breathing exercises, postures, and meditation-significantly improved sleep quality in cancer survivors. This study assessed the effects of YOCAS©® on memory and identified relationships between memory and sleep. Survivors were randomized to standard care (SC) or SC with YOCAS©® . 328 participants who provided data on the memory difficulty item of the MD Anderson Symptom Inventory are included. Sleep quality was measured using the Pittsburgh Sleep Quality Index. General linear modeling (GLM) determined the group effect of YOCAS©® on memory difficulty compared with SC. GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa. Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS©® changes in sleep and vice versa. YOCAS©® significantly reduced memory difficulty at postintervention compared with SC (mean change: yoga=-0.60; SC=-0.16; P<.05). Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS©® compared with SC. Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS©® compared with SC (P<.05). Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS©® compared with SC (P<.05); however, changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS©® compared with SC. In this large nationwide trial, YOCAS©® yoga significantly reduced patient-reported memory difficulty in cancer survivors. © The Author(s) 2015.

  3. Breast Cancer Affects Both the Hippocampus Volume and the Episodic Autobiographical Memory Retrieval

    PubMed Central

    Bergouignan, Loretxu; Lefranc, Jean Pierre; Chupin, Marie; Morel, Nastassja; Spano, Jean Philippe; Fossati, Philippe

    2011-01-01

    Background Neuroimaging studies show the hippocampus is a crucial node in the neural network supporting episodic autobiographical memory retrieval. Stress-related psychiatric disorders, namely Major Depression and Post Traumatic Stress Disorder (PTSD), are related to reduced hippocampus volume. However, this is not the case for remitted breast cancer patients with co-morbid stress-related psychiatric disorders. This exception may be due to the fact that, consequently to the cancer experience as such, this population might already be characterized by a reduced hippocampus with an episodic autobiographical memory deficit. Methodology We scanned, with a 3T Siemens TRIO, 16 patients who had lived through a “standard experience of breast cancer” (breast cancer and a standard treatment in remission since 18 month) in the absence of any associated stress-related psychiatric or neurological disorder and 21 matched controls. We then assessed their episodic autobiographical memory retrieval ability. Principal Findings Remitted breast cancer patients had both a significantly smaller hippocampus and a significant deficit in episodic autobiographical memory retrieval. The hippocampus atrophy was characterized by a smaller posterior hippocampus. The posterior hippocampus volume was intimately related to the ability to retrieve negative memories and to the past experience of breast cancer or not. Conclusions/Significance These results provide two main findings: (1) we identify a new population with a specific reduction in posterior hippocampus volume that is independent of any psychiatric or neurological pathology; (2) we show the intimate relation of the posterior hippocampus to the ability to retrieve episodic autobiographical memories. These are significant findings as it is the first demonstration that indicates considerable long-term effects of living through the experience of breast cancer and shows very specific hippocampal atrophy with a functional deficit without any

  4. AACR Honors Louis Staudt with Princess Takamatsu Memorial Lectureship | Center for Cancer Research

    Cancer.gov

    The American Association for Cancer Research has awarded Louis M. Staudt, Co-Chief of CCR’s Lymphoid Malignancies Branch, its Princess Takamatsu Memorial Lectureship. The lectureship recognizes scientists whose work has had or may have a far-reaching impact on the detection, diagnosis, treatment or prevention of cancer and who embody the dedication of the princess to multinational collaborations. Learn more...  

  5. Attention and memory deficits in breast cancer survivors: implications for nursing practice and research.

    PubMed

    Frank, Jennifer Sandson; Vance, David E; Jukkala, Angela; Meneses, Karen M

    2014-10-01

    Breast cancer survivors (BCSs) commonly report deficits in attention and memory, cognitive functions crucial for daily optimal functioning. Perceived deficits are reported before, during, and after adjuvant therapy and affect quality of life throughout survivorship. Deficits of attention and memory are particularly disruptive for BCSs working or attending school who report that subtle impairment diminishes their confidence and their performance at all levels of occupation. Chemotherapy and endocrine therapy contribute to attention and memory deficits, but research findings have not fully established the extent or timing of that influence. Fortunately, potential interventions for attention and memory deficits in BCSs are promising. These include cognitive remediation therapies aimed at training for specific areas of deficit, cognitive behavioral therapies aimed at developing compensatory strategies for areas of deficit, complementary therapies, and pharmacologic therapies.

  6. Randomized Phase II Trial of Adjuvant WT -1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    DTIC Science & Technology

    2016-09-01

    Chicago, IL - poster presented at Trials in Progress Session World Conference on Lung Cancer , Amsterdam, Jul 2011, slide presentation Meso Foundation...Scheinberg DA. WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer , Cancer ...Mesothelioma after Completion of Multimodality Therapy PRINCIPAL INVESTIGATOR: Dr. Marjorie Zauderer CONTRACTING ORGANIZATION: Sloan-Kettering Cancer

  7. Recall in Older Cancer Patients: Measuring Memory for Medical Information

    ERIC Educational Resources Information Center

    Jansen, Jesse; van Weert, Julia; van der Meulen, Nienke; van Dulmen, Sandra; Heeren, Thea; Bensing, Jozien

    2008-01-01

    Purpose: Remembering medical treatment information may be particularly taxing for older cancer patients, but to our knowledge this ability has never been assessed in this specific age group only. Our purpose in this study was to investigate older cancer patients' recall of information after patient education preceding chemotherapy. Design and…

  8. Recall in Older Cancer Patients: Measuring Memory for Medical Information

    ERIC Educational Resources Information Center

    Jansen, Jesse; van Weert, Julia; van der Meulen, Nienke; van Dulmen, Sandra; Heeren, Thea; Bensing, Jozien

    2008-01-01

    Purpose: Remembering medical treatment information may be particularly taxing for older cancer patients, but to our knowledge this ability has never been assessed in this specific age group only. Our purpose in this study was to investigate older cancer patients' recall of information after patient education preceding chemotherapy. Design and…

  9. Chromatin Memory in the Development of Human Cancers

    PubMed Central

    Yao, Yixin; Des Marais, Thomas L; Costa, Max

    2014-01-01

    Cancer is a complex disease with acquired genomic and epigenomic alterations that affect cell proliferation, viability and invasiveness. Almost all the epigenetic mechanisms including cytosine methylation and hydroxymethylation, chromatin remodeling and non-coding RNAs have been found associate with carcinogenesis and cancer specific expression profile. Altered histone modification as an epigenetic hallmark is frequently found in tumors. Understanding the epigenetic alterations induced by carcinogens or infectious agents may help us understand early epigenetic changes prior to the development of cancer. In this review, we focus on chromatin remodeling and the associated histone modifiers in the development of cancer; the application of these modifiers as a cancer therapy target in different clinical trial phases is also discussed. PMID:25606572

  10. Memories.

    ERIC Educational Resources Information Center

    Brand, Judith, Ed.

    1998-01-01

    This theme issue of the journal "Exploring" covers the topic of "memories" and describes an exhibition at San Francisco's Exploratorium that ran from May 22, 1998 through January 1999 and that contained over 40 hands-on exhibits, demonstrations, artworks, images, sounds, smells, and tastes that demonstrated and depicted the biological,…

  11. Memories.

    ERIC Educational Resources Information Center

    Brand, Judith, Ed.

    1998-01-01

    This theme issue of the journal "Exploring" covers the topic of "memories" and describes an exhibition at San Francisco's Exploratorium that ran from May 22, 1998 through January 1999 and that contained over 40 hands-on exhibits, demonstrations, artworks, images, sounds, smells, and tastes that demonstrated and depicted the biological,…

  12. Induction of resident memory T cells enhances the efficacy of cancer vaccine

    PubMed Central

    Nizard, Mevyn; Roussel, Hélène; Diniz, Mariana O.; Karaki, Soumaya; Tran, Thi; Voron, Thibault; Dransart, Estelle; Sandoval, Federico; Riquet, Marc; Rance, Bastien; Marcheteau, Elie; Fabre, Elizabeth; Mandavit, Marion; Terme, Magali; Blanc, Charlotte; Escudie, Jean-Baptiste; Gibault, Laure; Barthes, Françoise Le Pimpec; Granier, Clemence; Ferreira, Luis C. S.; Badoual, Cecile; Johannes, Ludger; Tartour, Eric

    2017-01-01

    Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them. PMID:28537262

  13. Induction of resident memory T cells enhances the efficacy of cancer vaccine.

    PubMed

    Nizard, Mevyn; Roussel, Hélène; Diniz, Mariana O; Karaki, Soumaya; Tran, Thi; Voron, Thibault; Dransart, Estelle; Sandoval, Federico; Riquet, Marc; Rance, Bastien; Marcheteau, Elie; Fabre, Elizabeth; Mandavit, Marion; Terme, Magali; Blanc, Charlotte; Escudie, Jean-Baptiste; Gibault, Laure; Barthes, Françoise Le Pimpec; Granier, Clemence; Ferreira, Luis C S; Badoual, Cecile; Johannes, Ludger; Tartour, Eric

    2017-05-24

    Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.

  14. Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer

    PubMed Central

    Bender, Catherine M.; Sereika, Susan M.; Brufsky, Adam M.; Ryan, Christopher M.; Vogel, Victor G.; Rastogi, Priya; Cohen, Susan M.; Casillo, Frances E.; Berga, Sarah L.

    2010-01-01

    Objective: Hormones have been implicated as modulators of cognitive functioning. For instance, results of our previous work in women with breast cancer showed that cognitive impairment was more severe and involved more memory domains in those who received adjuvant tamoxifen therapy compared with women who received chemotherapy alone or no adjuvant therapy. Recently aromatase inhibitors such as anastrozole have been used in lieu of tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor–positive, early-stage breast cancer. Plasma estrogen levels are significantly lower in women who receive anastrozole compared with those who receive tamoxifen. We hypothesized, therefore, that anastrozole would have a more profound effect on cognitive function than tamoxifen, a mixed estrogen agonist/antagonist. Design: To test this hypothesis we compared cognitive function in women with early-stage breast cancer who received tamoxifen with those who received anastrozole therapy in a cross-sectional study. We evaluated cognitive function, depression, anxiety, and fatigue in 31 postmenopausal women with early-stage breast cancer who were between the ages of 21 and 65 years and treated with tamoxifen or anastrozole for a minimum of 3 months. Results: The results showed that women who received anastrozole had poorer verbal and visual learning and memory than women who received tamoxifen. Conclusions: Additional, prospective studies are needed to validate and confirm the changes in cognitive function associated with hormone therapy for breast cancer. PMID:17898668

  15. Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells

    PubMed Central

    Bae, Jooeun; Samur, Mehmet; Munshi, Aditya; Hideshima, Teru; Keskin, Derin; Kimmelman, Alec; Lee, Ann-Hwee; Dranoff, Glen; Anderson, Kenneth C; Munshi, Nikhil C

    2015-01-01

    XBP1 is a critical transcriptional activator of the unfolded protein response (UPR), which increases tumor cell survival under prolonged endoplasmic reticulum (ER) stress and hypoxic conditions.This study was designed to evaluate the immunogenicity of heteroclitic XBP1 unspliced (US)184–192 (YISPWILAV) and heteroclictic XBP1 spliced (SP)367–375 (YLFPQLISV) HLA-A2 peptides, and to characterize the specific activities of XBP1 peptides-specific cytotoxic T lymphocytes (XBP1-CTL) against breast cancer, colon cancer, and pancreatic cancer cells.The XBP1-CTL had upregulated expression of critical T cell markers and displayed HLA-A2-restricted and antigen-specific activities against breast cancer, colon cancer and pancreatic cancer cells. XBP1-CTL were enriched withCD45RO+ memory CTL, which showed high expression of critical T cell markers (CD28, ICOS, CD69, CD40L), cell proliferation and antitumor activities as compared to CD45RO− non-memory CTL. The effector memory (EM: CD45RO+CCR7−) subset had the highest level of cell proliferation while the central memory (CM: CD45RO+CCR7+) subset demonstrated enhanced functional activities (CD107a degranulation, IFNγ/IL-2 production) upon recognition of the respective tumor cells. Furthermore, both the EM and CM XBP1-CTL subsets expressed high levels of Th1 transcription regulators Tbet and Eomes. The highest frequencies of IFNγ or granzyme B producing cells were detected within CM XBP1-CTL subset that were either Tbet+ or Eomes+ in responding to the tumor cells.These results demonstrate the immunotherapeutic potential of a cocktail of immunogenic HLA-A2 specific heteroclitic XBP1 US184–192 and heteroclictic XBP1 SP367–375 peptides to induce CD3+CD8+ CTL enriched for CM and EM cells with specific antitumor activities against a variety of solid tumors. PMID:25941601

  16. Integrative oncology: the last ten years--a personal retrospectve.

    PubMed

    Boyd, D Barry

    2007-01-01

    In the last decade, there has been dramatic changes in all areas of integrative patient care. None has been more dramatic than those in the field of cancer care, which has gone from alternative and complementary treatments delivered outside the conventional setting to the integration of many of these approaches into the care of the cancer patient. In many cases, these changes have been driven by patient demand and supported by private funding and out-of-pocket payments by patients themselves. Virtually all major medical centers have departments devoted to integrative patient care--whether true stand-alone centers or departments with a research interest in this area. This is particularly true of the major cancer centers, many of which-including Memorial Sloan Kettering Cancer Center, New York; M.D. Anderson Cancer Center, Houston, Tex; Johns Hopkins University, Baltimore, Md; Duke University, Durham, NC; and the Dana Farber Cancer Institute, Boston, Mass--have developed integrative cancer programs. In addition, programs such as the Cancer Treatment Centers of America have inpatient and outpatient programs with teams of practitioners, including medical oncologists, surgeons, and radiation therapists, as well as credentialed naturopathic doctors, nutritionists, mind-body specialists and other integrative practitioners. Despite the increased interest in developing integrative approaches to cancer, many medical oncologists remain skeptical about the value of these modalities.

  17. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy.

    PubMed

    Naidoo, Jarushka; Wang, Xuan; Woo, Kaitlin M; Iyriboz, Tunc; Halpenny, Darragh; Cunningham, Jane; Chaft, Jamie E; Segal, Neil H; Callahan, Margaret K; Lesokhin, Alexander M; Rosenberg, Jonathan; Voss, Martin H; Rudin, Charles M; Rizvi, Hira; Hou, Xue; Rodriguez, Katherine; Albano, Melanie; Gordon, Ruth-Ann; Leduc, Charles; Rekhtman, Natasha; Harris, Bianca; Menzies, Alexander M; Guminski, Alexander D; Carlino, Matteo S; Kong, Benjamin Y; Wolchok, Jedd D; Postow, Michael A; Long, Georgina V; Hellmann, Matthew D

    2017-03-01

    Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patients who received anti-PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5%; 95% CI, 3% to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P < .01). Incidence was similar in patients with melanoma and non-small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [ P = 1.0]; combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion

  18. Stress, Psychosocial Mediators, and Cognitive Mediators in Parents of Child Cancer Patients and Cancer Survivors: Attention and Working Memory Pathway Perspectives.

    PubMed

    Vander Haegen, Marie; Luminet, Olivier

    2015-01-01

    This review examines stress and its consequences on attention and working memory, stress symptoms in parents of child cancer patients and survivors and long-term consequences of stress on cognitive processing in parents of child cancer survivors. Eligible studies were experimental, meta-analyses, and qualitative (2000-2013) from Pubmed, Medline, the Cochrane Library, PsycArticles, and Google Scholar. We identified 92 eligible papers. They showed that elevated stress can impede performances on tasks requiring attention and memory patterns. In pediatric oncology, parental stress increased shortly after diagnosis involving depression and anxiety. Consequences of stress on cognitive performances were observed mainly among depressed individuals. As regards parents of child cancer survivors, female gender, low Socioeconomic Status (SES), and innate traits of anxiety/anger predicted the development of PTSS. Evidence of stress on attention and working memory processes in parents of child cancer survivors is insufficiently developed.

  19. Blocking Glycolytic Metabolism Increases Memory T Cells and Antitumor Function | Center for Cancer Research

    Cancer.gov

    CD8+ T cells are a major component of the cellular immune response, which is necessary to control a variety of bacterial and viral infections. CD8+ T cells also play a major role in the cell-mediated antitumor immune response. After encountering antigen, naïve CD8+ T cells undergo an extensive period of proliferation and expansion, and differentiate into effector cells and distinct memory T cell subsets. Preclinical studies using adoptive transfer of purified CD8+ T cells have shown that the ability of T cells to proliferate and survive for a long time after transfer is associated with effective antitumor and antiviral responses. Understanding how the formation of long-lived memory T cell subsets is controlled may enable development of more potent immunotherapies against cancer and infectious diseases.

  20. Delivering Coordinated Cancer Care by Building Transactive Memory in a Team of Teams.

    PubMed

    Henry, Elizabeth; Silva, Abigail; Tarlov, Elizabeth; Czerlanis, Cheryl; Bernard, Margie; Chauhan, Cynthia; Schalk, Denise; Stewart, Greg

    2016-11-01

    Cancer care delivery is highly complex. Treatment involves coordination within oncology health-care teams and across other teams of referring primary and specialty providers (a team of teams). Each team interfaces with patients and caregivers to offer component parts of comprehensive care. Because patients frequently obtain specialty care from divergent health-care systems resulting in cross-system health-care use, oncology teams need mechanisms to coordinate and collaborate within and across health-care systems to optimize clinical outcomes for all cancer patients. Transactive memory is one potential strategy that can help improve comprehensive patient care delivery. Transactive memory is a process by which two or more team professionals develop a shared system for encoding, storing, and retrieving information. Each professional is responsible for retaining only part of the total information. Applying this concept to a team of teams results in system benefits wherein all teams share an understanding of specialized knowledge held by each component team. The patient's role as the unifying member of the team of teams is central to successful treatment delivery. This clinical case presents a patient who is receiving oral treatment for advanced prostate cancer within two health systems. The case emphasizes the potential for error when multiple teams function without a point team (the team coordinating efforts of all other primary and specialty teams) and when the specialty knowledge of providers and patients is not well integrated into all phases of the care delivery process.

  1. Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors

    PubMed Central

    Cheng, Huaidong; Li, Wen; Gong, Liang; Xuan, Han; Huang, Zhonglian; Zhao, Hong; Wang, Long Sheng; Wang, Kai

    2017-01-01

    In this study, we aimed to investigate the intrinsic hippocampal functional connectivity (FC) network and its relationship with prospective memory in patients with breast cancer suffering from chemotherapy-induced cognitive impairment (CICI). Thirty-four breast cancer patients before and after adjuvant chemotherapy (CB and CC, respectively) and 31 age- and education-matched cognitively normal (CN) women were recruited and subjected to a prospective memory task and a resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity analysis was used to compare the hippocampal FC networks between CC and CN groups. Partial correction analysis was used to examine the association between the hippocampal FC network and prospective memory in the CC group. The cancer group that underwent chemotherapy obtained significantly poorer scores than the CN group on mini-mental state examination, verbal fluency test, digit span, and prospective memory examination. Compared to the CN group, CC group showed increased hippocampal connectivity in the frontal and parietal cortex, precuneus, posterior cingulate cortex, and the cerebellum. In addition, the increasing hippocampal FC networks were negatively correlated with prospective memory performance in the CC group. These findings suggest maladaptive hippocampal functioning as a mechanism underlying the impairment of prospective memory in patients experiencing CICI. PMID:28327626

  2. Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors.

    PubMed

    Cheng, Huaidong; Li, Wen; Gong, Liang; Xuan, Han; Huang, Zhonglian; Zhao, Hong; Wang, Long Sheng; Wang, Kai

    2017-03-22

    In this study, we aimed to investigate the intrinsic hippocampal functional connectivity (FC) network and its relationship with prospective memory in patients with breast cancer suffering from chemotherapy-induced cognitive impairment (CICI). Thirty-four breast cancer patients before and after adjuvant chemotherapy (CB and CC, respectively) and 31 age- and education-matched cognitively normal (CN) women were recruited and subjected to a prospective memory task and a resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity analysis was used to compare the hippocampal FC networks between CC and CN groups. Partial correction analysis was used to examine the association between the hippocampal FC network and prospective memory in the CC group. The cancer group that underwent chemotherapy obtained significantly poorer scores than the CN group on mini-mental state examination, verbal fluency test, digit span, and prospective memory examination. Compared to the CN group, CC group showed increased hippocampal connectivity in the frontal and parietal cortex, precuneus, posterior cingulate cortex, and the cerebellum. In addition, the increasing hippocampal FC networks were negatively correlated with prospective memory performance in the CC group. These findings suggest maladaptive hippocampal functioning as a mechanism underlying the impairment of prospective memory in patients experiencing CICI.

  3. Interview with Dr Ghassan K Abou-Alfa.

    PubMed

    Abou-Alfa, G K

    2016-11-01

    Ghassan K Abou-Alfa joined the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York back in 2001. Dr Abou-Alfa specializes in the treatment of gastrointestinal malignancies. Dr Abou-Alfa received his medical degree from the American University of Beirut, Lebanon, and completed his post-doctoral training at Yale University School of Medicine. His research is dedicated to finding novel therapies and improving the effectiveness of the current therapies for hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, while continuing to understand the basic mechanisms of the diseases and its therapy. Dr Abou-Alfa has invested several years in helping develop multi-tyrosine kinases and more immune-modulator therapies. Dr Abou-Alfa has many publications in the field. He led on many occasions international teams of investigators. Dr Abou-Alfa serves as the chair of the National Cancer Institute (NCI) Task Force for Hepatobiliary Cancers and the chair of the AIDS Malignancy Consortium (AMC) Non-AIDS Defining Malignancies (NADC) Liver/GI Task Force. Dr Abou-Alfa also co-chairs the hepatobiliary cancers subgroup of the Alliance cooperative group, and is a cadre member of both the gastrointestinal cancers and pharmacogenomics and population pharmacology committees. Dr Abou-Alfa who has lectured worldwide on the subject on gastrointestinal malignancies, is also a strong advocate for raising awareness and support for improving the outcome of patients with this disease, and enhancing oncologic education worldwide.

  4. Concentration, working speed and memory: cognitive problems in young childhood cancer survivors and their siblings.

    PubMed

    Wengenroth, L; Rueegg, C S; Michel, G; Gianinazzi, M E; Essig, S; von der Weid, N X; Grotzer, M; Kuehni, Claudia E

    2015-05-01

    Cognitive problems can have a negative effect on a person's education, but little is known about cognitive problems in young childhood cancer survivors (survivors). This study compared cognitive problems between survivors and their siblings, determined if cognitive problems decreased during recent treatment periods and identified characteristics associated with the presence of a cognitive problem in survivors. As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was sent to all survivors, aged 8-20 years, registered in the Swiss Childhood Cancer Registry, diagnosed at age <16 years, who had survived ≥ 5 years. Parent-reported (aged 8-15 years) and self-reported (aged 16-20 years) cognitive problems (concentration, working speed, memory) were compared between survivors and siblings. Multivariable logistic regression was used to identify characteristics associated with cognitive problems in survivors. Data from 840 survivors and 247 siblings were analyzed. More often than their siblings, survivors reported problems with concentration (12% vs. 6%; P = 0.020), slow working speed (20% vs. 8%; P = 0.001) or memory (33% vs. 15%; P < 0.001). Survivors from all treatment periods were more likely to report a cognitive problem than were siblings. Survivors of CNS tumors (OR = 2.82 compared to leukemia survivors, P < 0.001) and those who had received cranial irradiation (OR = 2.10, P = 0.010) were most severely affected. Childhood cancer survivors, even those treated recently (2001-2005), remain at risk to develop cognitive problems, suggesting a need to improve therapies. Survivors with cognitive problems should be given the opportunity to enter special education programs. © 2015 Wiley Periodicals, Inc.

  5. Hand-foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib.

    PubMed

    Nakano, Kazuhiko; Komatsu, Kenji; Kubo, Taro; Natsui, Shinsuke; Nukui, Akinori; Kurokawa, Shinsuke; Kobayashi, Minoru; Morita, Tatsuo

    2013-10-01

    To elucidate whether Hand-Foot skin reaction could become a biomarker of clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib, we retrospectively examined the association between the Hand-Foot skin reaction and the clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib. Thirty-six Japanese metastatic renal cell carcinoma patients treated with sorafenib were enrolled and divided into the groups with or without Hand-Foot skin reaction. Patient characteristics, best tumor response, progression-free survival and adverse events were investigated and compared between these two groups. A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients was observed at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative Oncology Group Performance Status of one or less, prior nephrectomy, higher hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean best tumor response was significantly better in the group with Hand-Foot skin reaction (-16.7%) than that in the group without it (17.9%; P < 0.001). The median progression-free survival was significantly longer in the group with Hand-Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P = 0.002). In multivariate analysis, only Hand-Foot skin reaction was shown to be a predictive factor of progression-free survival (hazard ratio 0.312, P = 0.010). A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients emerged at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification and was significantly associated with best tumor response and progression-free survival, suggesting that Hand-Foot skin reaction might be an independent predictive factor for clinical outcome in metastatic renal

  6. An investigation of vancomycin-resistant Enterococcus faecium within the pediatric service of a large urban medical center.

    PubMed

    McNeeley, D F; Brown, A E; Noel, G J; Chung, M; De Lencastre, H

    1998-03-01

    Between 1990 to 1992 and 1993 to 1995 there was a >5-fold increase (16.7% to 89.8%) in vancomycin-resistant Enterococcus faecium isolates as a percentage of all isolates of vancomycin-resistant enterococci on the pediatric units of The New York Hospital-Cornell Medical Center (NYH-CMC). A molecular epidemiologic investigation was undertaken to determine the extent to which this increase was associated with the spread of a vanA-containing clone of vancomycin-resistant E. faecium that had been previously defined in adults hospitalized at NYH-CMC or with the spread of another vanA clone that had been defined in children hospitalized on the pediatric service at Memorial Sloan-Kettering Cancer Center, which shares a common pediatric intensive care unit and pediatric house staff with NYH-CMC. Molecular genotyping of vancomycin-resistant E. faecium isolates obtained from pediatric patients from 1993 to 1995 was performed by pulsed field gel electrophoresis of chromosomal SmaI digests. Southern hybridization was performed using vanA- and vanB-specific probes. Medical records of patients were reviewed for pertinent clinical and demographic information. A single vanB clone of vancomycin-resistant E. faecium was responsible for 17 (77.3%) of 22 isolates in the neonatal intensive care unit (NICU) of NYH-CMC. Two other vanB strains of vancomycin-resistant E. faecium and 2 vanA strains were identified among the 5 remaining NICU isolates. Vancomycin-resistant E. faecium isolates from the other pediatric units represented a heterogeneous population of primarily vanA strains, but vanA clonal strains previously identified from patients on adult services at NYH-CMC and from children hospitalized at Memorial Sloan-Kettering Cancer Center were not detected. A newly identified vanB clone was responsible for the increase in vancomycin-resistant E. faecium isolates in the NICU of NYH-CMC. The increase of vancomycin-resistant E. faecium among children hospitalized at NYH-CMC was unrelated

  7. Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells.

    PubMed

    Paroli, Marino; Bellati, Filippo; Videtta, Melissa; Focaccetti, Chiara; Mancone, Carmine; Donato, Tiziana; Antonilli, Morena; Perniola, Giorgia; Accapezzato, Daniele; Napoletano, Chiara; Nuti, Marianna; Bartolazzi, Armando; Panici, Pierluigi Benedetti; Tripodi, Marco; Palombo, Fabio; Barnaba, Vincenzo

    2014-04-15

    According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8(+) and CD4(+) T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4(+) and CD8(+) T cells producing either IFN-γ or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines. © 2013 UICC.

  8. Treating metastatic melanoma in 2014: what just happened and what is next?

    PubMed

    Chapman, Paul B

    2014-01-01

    In recent years the expectation related to treating patients with metastatic melanoma has changed. Three years ago, a diagnosis of metastatic melanoma was bleak; only a small number of patients would benefit from standard treatment and the reason for treatment benefit was often unknown, leaving physicians with limited options to help their patients. Today, just 3 years later, there are proven therapies that allow physicians to expect to shrink tumors and extend the lives of their patients after diagnosis. In this article, Paul B. Chapman, MD, Memorial Sloan Kettering Cancer Center, summarizes the recent advances in the field of metastatic melanoma and looks ahead to topics such as focusing on specificity, shutting down the ERK pathway, intermittent dosing, discovering driver mutations, individualizing checkpoint inhibition, and identifying rejection antigens to identify what should occur next in order to continue to improve outcomes for a larger population of patients with metastatic melanoma. Dr. Chapman's paper reminds us of the exciting progress that has been made while focusing on the work that is left in the field. Dr. Chapman is a physician-scientist who specializes in diagnosing and treating melanoma that has metastasized to other parts of the body. Dr. Chapman led a clinical trial that paved the way, in part, to the approval of vemurafenib-a drug that targets a BRAF mutation that is present in approximately 50% of patients with metastatic melanoma. Dr. Chapman is one of five Memorial Sloan Kettering scientists to be appointed to a melanoma "Dream Team" that focuses on identifying potential therapies for metastatic melanoma patients who do not have the mutated form of the BRAF gene. Dr. Chapman is also a professor of medicine at the Weill Cornell Medical College and is the chair of the Melanoma Research Alliance Medical Advisory Board. In addition to the above, Dr. Chapman is a sought-after mentor for medical oncology fellows and has a current research

  9. The Public Health Impact of Herbs and Nutritional Supplements

    PubMed Central

    Cassileth, Barrie R.; Heitzer, Marjet; Wesa, Kathleen

    2009-01-01

    Dietary supplement use has increased exponentially in recent years despite the lack of regulatory oversight and in the face of growing safety concerns. This paper provides an overview of the public health implications and safety concerns associated with dietary supplement use, especially by cancer patients. Botanical research is actively pursued at the Memorial Sloan-Kettering Cancer Center (MSKCC) Integrative Medicine department. Work of the MSKCC Center for the Study of Botanical Immunomodulators is described, and guidelines for cancer patients’ use of dietary supplements outlined. Herbs and other botanicals are complex, physiologically active agents, but little is known about most of the popular, widely available dietary supplements. Herb-drug interactions, a major concern, are exacerbated in the cancer setting. Biologically active agents may interfere with chemotherapy and other prescription medications. They may exert anti-coagulant activity at rather inconvenient times such as during surgery, and create other serious problems. Research on the bioavailability, effective dosage, safety and benefits of these complex agents is sorely needed. Oncology professionals and other healthcare providers should educate themselves and their patients about these issues. Probably the largest, continuously-updated free information resource is MSKCC’s AboutHerbs website (www.mskcc.org/AboutHerbs). PMID:19890479

  10. Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.

    PubMed

    de Velasco, Guillermo; Miao, Diana; Voss, Martin H; Hakimi, A Ari; Hsieh, James J; Tannir, Nizar M; Tamboli, Pheroze; Appleman, Leonard J; Rathmell, W Kimryn; Van Allen, Eliezer M; Choueiri, Toni K

    2016-10-01

    Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genes-granzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. Cancer Immunol Res; 4(10); 820-2. ©2016 AACR.

  11. Interstitial radiation: short-term palliation or curative therapy?

    PubMed

    Whitmore, W F; Hilaris, B; Batata, M; Sogani, P; Herr, H; Morse, M

    1985-02-01

    The management of clinically localized prostatic cancer by interstitial implantation of 125I seeds has been under exploration at Memorial Sloan-Kettering Cancer Center for thirteen years. This investigation was prompted by clinical evidence of the radioresponsiveness of some prostatic cancers, the limited applicability of surgical excision, and the possibility that interstitial therapy would have less of an adverse effect on the quality of life than would alternative treatments. Cumulative experience indicates that the technique is associated with low morbidity and mortality and high functional preservation rates; local control rates (routine biopsies were not done), within the constraints of still-limited follow-up intervals, are in the 80 per cent to 90 per cent range; and actuarial survival rates at nine years (including patients who received endocrine therapy for metastatic or intractable local disease) are approximately 90 per cent for T1, 60 per cent for T2, and 45 per cent for T3 lesions. Approximate actuarial nine-year survival rates are 80 per cent for all patients with negative nodes and 50 per cent for all patients with positive nodes. Taking into account limitations of the data and the hazards of comparing this therapy with other uncontrolled treatments, 125I appears to be a therapeutic option for the control of clinically localized prostatic cancer.

  12. A Pilot Study of Website Information Regarding Aromatase Inhibitors: Dietary Supplement Interactions

    PubMed Central

    McDermott, Cara L.; Hsieh, Angela A.; Sweet, Erin S.; Tippens, Kimberly M.

    2011-01-01

    Abstract Objectives Patients who have hormone receptor–positive breast cancer and who are taking aromatase inhibitors (AIs) should understand the benefits and risks of concomitant dietary supplement (DS) use. The International Society for Integrative Oncology (SIO) encourages patients to discuss DS use with their health care practitioners. The objective was to conduct a pilot study rating Internet websites from the perspective of health care practitioners for information about AI–DS interactions. Design Five (5) Internet websites suggested by SIO were evaluated using the DISCERN instrument rating tool. The available AI–DS information on these websites was rated by 4 evaluators: 2 naturopathic doctors, 1 oncology pharmacy resident, and a pharmacy student. Results The overall rankings ranged from 1.6 to 3.9, with considerable variability in the type of information available from the websites. The interevaluator rankings of the websites ranged from 0.44 to 0.89. The evaluators consistently found the most reliable, unbiased, and comprehensive information on AI–DS interactions at the Natural Medicines Comprehensive Database and Memorial Sloan-Kettering Cancer Center websites. However, more than one database was needed for provision of optimal patient information on AI–DS interactions. Conclusions In order to effectively advise patients regarding AI–DS interactions, more than one website should be evaluated to assess the potential efficacy and safety of DS in women whose breast cancer is being treated with an AI. PMID:22087614

  13. Associations Between Physical Fitness Indices and Working Memory in Breast Cancer Survivors and Age-Matched Controls

    PubMed Central

    Mackenzie, Michael J.; Zuniga, Krystle E.; Raine, Lauren B.; Awick, Elizabeth A.; Hillman, Charles H.; Kramer, Arthur F.

    2016-01-01

    Abstract Background: This study examined the effects of cardiorespiratory fitness, heart rate recovery, and physical activity on working memory in breast cancer survivors and age-matched controls. Method: Using a case-control design, 32 women who had received a breast cancer diagnosis and completed primary treatment within the past 36-months (11 radiation only; 21 chemotherapy) and 30 age-matched women with no previous cancer diagnosis completed a n-back continuous performance task commonly used as an assessment of working memory. In addition, cardiorespiratory fitness and heart rate recovery were measured during a submaximal graded exercise test and physical activity was measured using 7-days of accelerometer monitoring. Results: Breast cancer survivors who had received chemotherapy had poorer heart rate recovery (p = .010) and engaged in less physical activity than women who had received radiation only (p = .004) or non-cancer controls (p = .029). Cancer treatment (radiation; chemotherapy) predicted differences in reaction times on the 1-back working memory task (p = .029). However, more rapid heart rate recovery predicted shorter reaction times on the 1-back task in the age-matched control group (p = .002). All participants with greater cardiorespiratory fitness displayed greater accuracy independent of disease status on the 1-back task (p = .017). No significant group differences in reaction times were observed for 2-back target trials between breast cancer survivors and controls. However, greater total physical activity predicted shorter reaction times in breast cancer survivors (radiation, chemotherapy) on the 2-back task (p = .014). In addition, all participants who exhibited more rapid heart rate recovery demonstrated better greater accuracy regardless of disease status (p = .013). Conclusion: These findings support differences in physical activty participation, heart rate recovery, and 1- and 2-back working memory reaction

  14. Reactivation of CDX2 in Gastric Cancer as Mark for Gene Silencing Memory

    PubMed Central

    Kameoka, Yuri; Kitazawa, Riko; Ariasu, Kanazu; Tachibana, Ryosuke; Mizuno, Yosuke; Haraguchi, Ryuma; Kitazawa, Sohei

    2015-01-01

    To explore the epigenetic mechanism that reactivates CDX2 (a homeobox transcription factor that serves as a tumor-suppressor gene) in intestinal-type gastric cancer during cancer progression, we examined the methylation status of the CDX2 gene promoter and the expression pattern of methyl-CpG binding protein-2 (MeCP2). From archives of the pathology records of surgically excised advanced stomach cancer cases in the Department of Molecular Pathology, Ehime University in a past decate (n=265), 10 cases of intestinal-type tubular adenocarcinoma, well-differentiated type (wel) with minor poorly-differentiated adenocarcinoma (por) components were selected. The expression pattern of CDX2, MUC2 and MeCP2 in these 10 cases was analyzed by immunohistochemistry. The cancerous and non-cancerous areas were selectively obtained by microdissection, and the methylation status of the CDX2 promoter of each area was assessed by methylation-specific polymerase chain reaction (MSP). In all 10 cases, CDX2 expression was clearly observed in the nucleus of the non-cancerous background of the intestinal metaplasic area, where the unmethylation pattern of the CDX2 gene promoter prevailed with reduced MeCP2 expression. In this metaplastic area, CDX2 expression was co-localized with its target gene, MUC2. CDX2 expression then disappeared from the deep invasive wel area. Reflecting the reduced CDX2 expression, microdissected samples from all the wel areas showed hypermethylation of the CDX2 gene promoter by MSP, with prominent MeCP2 expression. Interestingly, while hypermethylation of the CDX2 gene promoter was maintained in the por area in 8 of the 10 cases, CDX2 expression was restored in por areas where MeCP2 expression was markedly and selectively reduced. The other two cases, however, showed a constant MeCP2 expression level comparable to the surrounding deep invasive wel area with negative CDX2 expression. Therefore, gene silencing by hypermethylation may be overcome by the reduction of

  15. A Novel Prostate Cancer Classification Technique Using Intermediate Memory Tabu Search

    NASA Astrophysics Data System (ADS)

    Tahir, Muhammad Atif; Bouridane, Ahmed; Kurugollu, Fatih; Amira, Abbes

    2005-12-01

    The introduction of multispectral imaging in pathology problems such as the identification of prostatic cancer is recent. Unlike conventional RGB color space, it allows the acquisition of a large number of spectral bands within the visible spectrum. This results in a feature vector of size greater than 100. For such a high dimensionality, pattern recognition techniques suffer from the well-known curse of dimensionality problem. The two well-known techniques to solve this problem are feature extraction and feature selection. In this paper, a novel feature selection technique using tabu search with an intermediate-term memory is proposed. The cost of a feature subset is measured by leave-one-out correct-classification rate of a nearest-neighbor (1-NN) classifier. The experiments have been carried out on the prostate cancer textured multispectral images and the results have been compared with a reported classical feature extraction technique. The results have indicated a significant boost in the performance both in terms of minimizing features and maximizing classification accuracy.

  16. Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest.

    PubMed

    Myskowski, P L; Gumpertz, E; Safai, B

    1985-03-01

    A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. She recalled that she had faced the fluoroscopy beam during the procedure. In 1959, she had a transabdominal hysterectomy for fibroid tumors. In 1980 she underwent a right modified radical mastectomy for adenoid cystic carcinoma of the breast; biopsies of lymph nodes were negative. Physical examination revealed a thin, white woman with a right mastectomy scar. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. There were no other suspicious lesions on the head, chest, or extremities, nor did the patient show any evidence of the basal cell nevus syndrome. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results (Fig. 1).

  17. Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors

    PubMed Central

    Anur, Praveen; Friedman, Danielle N; Sklar, Charles; Oeffinger, Kevin; Castiel, Mercedes; Kearney, Julia; Singh, Bhuvanesh; Prockop, Susan E; Kernan, Nancy A; Scaradavou, Andromachi; Kobos, Rachel; Curran, Kevin; Ruggiero, Julianne; Zakak, Nicole; O’Reilly, Richard J; Boulad, Farid

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least one year post-HSCT. Patients underwent either a total body irradiation (TBI) (N=18) or busulfan (N=4) based cytoreduction followed by T-cell depleted transplants from alternative donors. Twenty patients were alive at time of study with a 5 and 10 year overall survival of 100% and 84% and no evidence of chronic GVHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, four (22%) developed hypothyroidism, seven (39%) had insulin resistance and five (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism, and gonadal dysfunction after Busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes. PMID:26999465

  18. Experience with interstitial implantation of iodine 125 in the treatment of prostatic carcinoma.

    PubMed

    Sogani, P C; Whitmore, W F; Hilaris, B S; Batata, M A

    1980-01-01

    Between February 1970 and April 1977 300 patients with localized prostatic carcinoma were treated with I-125 implantation and bilateral pelvic lymphadenectomy at Memorial Sloan-Kettering Cancer Center (MSKCC). 68% had clinical Stage B (T-1 and T-2) and 32% had Stage C (T-3) neoplasms. Pelvic lymph nodes were histologically positive in 38% of the patients. Five-year survival for all patients was 73%. Five-year survival for Stage B disease was 100% and Stage C 65%. Lymph node metastases implied a poor prognosis. While 92% of patients with negative nodes survived five years, only 46% of the patients with positive nodes did so. Supplemental external radiation to pelvic and periaortic region in 28 patients with positive nodes did not improve survival or disease free interval or reduce distal or local recurrence but rather increased the incidence of radiation morbidity. The complications and morbidity as a consequence of I-125 implantation are minimal. The ultimate role of I-125 implantation in the management of localized prostatic cancer is yet to be determined. The early experience with this technique, however, suggests that it may be as effective as alternative modalities for comparable stages in terms of patient survival and may prove superior in terms of the quality of survival.

  19. Laparoscopy in the management of gastric adenocarcinoma.

    PubMed Central

    Burke, E C; Karpeh, M S; Conlon, K C; Brennan, M F

    1997-01-01

    OBJECTIVE: The authors determined the accuracy of laparoscopy in detecting metastatic disease in patients with gastric adenocarcinoma. SUMMARY BACKGROUND DATA: The majority of patients with gastric adenocarcinoma in the United States present with advanced disease. They are at high risk for intraabdominal metastatic spread. METHODS: One hundred eleven patients with gastric adenocarcinoma underwent laparoscopy at Memorial-Sloan Kettering Cancer Center from December 1991 to December 1995. All were judged to be free of intra-abdominal metastatic disease on preoperative computed tomographic scan imaging. RESULTS: Laparoscopic exploration was successful in 110 of 111 patients and accurately staged 94% of the patients with respect to metastatic disease with a sensitivity of 84% and a specificity of 100%. The prevalence rate of metastatic disease was 37%. Twenty-four patients underwent laparoscopy only and were discharged in an average 1.4 days versus 6.5 days in patients undergoing exploratory laparotomy without resection (p < 0.05). No patients undergoing laparoscopy only have returned for palliative surgery. CONCLUSIONS: Laparoscopy should be performed in nonobstructed, nonbleeding patients with advanced gastric cancer in the United States. More than one third of these patients have unsuspected metastatic disease at time of operation. Laparoscopy is highly accurate in detecting occult metastases and identifies a unique population of stage IV patients who may benefit from newer induction chemotherapeutic approaches while avoiding unnecessary laparotomy. Images Figure 4. PMID:9060581

  20. Squamous Cell Carcinoma of the Oral Tongue in the Pediatric Age Group

    PubMed Central

    Morris, Luc G. T.; Patel, Snehal G.; Shah, Jatin P.; Ganly, Ian

    2010-01-01

    Objective To compare outcomes of a pediatric cohort of patients compared with a matched cohort of adult patients, all diagnosed as having squamous cell carcinoma (SCC) of the oral tongue. Outcomes of oral cancer in pediatric patients have not been studied, to our knowledge. Design Retrospective matched-pair cohort study. Setting Memorial Sloan-Kettering Cancer Center, New York, New York. Patients A total of 10 pediatric and 40 adult patients diagnosed as having SCC of the oral tongue. Main Outcome Measures Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). Results The 5-year OS was equivalent in the 2 groups: 70% in the pediatric group and 64% in the adult group (P=.97). The 5-year DSS was also equivalent: 80% in the pediatric group and 76% in the adult group (P=.90). The 5-year RFS was 70% in the pediatric group and 78% in the adult group (P=.54). Conclusions When pediatric and adult patients were matched for sex, tobacco use history, TNM status, surgical procedure, and adjuvant radiotherapy, outcomes for OS, DSS, and RFS were equivalent. Pediatric patients with SCC of the oral tongue should be treated similarly to adult patients. PMID:20644066

  1. Rehabilitation of maxillectomy defects with obturator prostheses fabricated using computer-aided design and rapid prototyping: a pilot study.

    PubMed

    Jiao, Ting; Zhu, Chenyuan; Dong, Xian; Gu, Xiaoyu

    2014-01-01

    To establish an alternative method to design and fabricate an obturator prosthesis within the maxillectomy defect using a computer-aided design (CAD) and rapid prototyping (RP) technique and to evaluate the functional results of this technique. Eleven patients with acquired maxillary defects resulting from head and neck cancers were treated using a protocol based on three-dimensional (3D) reconstruction, CAD, and RP technologies to fabricate obturator prostheses. To evaluate the quality of the obturator prostheses and the patients' satisfaction, the Obturator Functioning Scale (OFS) of the Memorial Sloan-Kettering Cancer Center was applied. Each patient received an individualized obturator that exactly matched the static shape and fit of the defect. Clinical modifications were required to improve border contours. The patients showed good results in all fields of functional outcomes and social acceptance. The OFS scores were comparable with those reported in other studies using traditional maxillectomy impression methods. This study combined CAD with RP technology to explore an alternative and feasible method for manufacturing individualized obturators for patients after maxillary resection. It has shown significant clinical value, especially for use in developing countries.

  2. Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma.

    PubMed

    Morosán, Yanina Jimena; Parisi, Carina; Urrutia, María Agustina; Rosmarin, Melanie; Schnitman, Marta; Serrano, Leonardo; Luciani, Wilfrido; Faingold, Cristina; Pitoia, Fabián; Brenta, Gabriela

    2016-08-01

    The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

  3. Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest

    SciTech Connect

    Myskowski, P.L.; Gumpertz, E.; Safai, B.

    1985-03-01

    A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results.

  4. EPA Recognized for Research on Reducing Risks to Drinking ...

    EPA Pesticide Factsheets

    Technical Brief Threat Ensemble Vulnerability Assessment (TEVA) among finalists for Edelman Award On February 7, 2008, the Institute for Operations Research and the Management Sciences (INFORMS ® of Hanover, MD) announced that a TEVA Research project is one of six finalists vying for this year’s prestigious Franz Edelman Award. The project is called “Reducing Security Risks in American Drinking Water Systems.” Edelman Award Information This is the thirty-seventh year of the Edelman competition. Every year, the competition recognizes outstanding operations research-based projects that transform companies, entire industries, and people’s lives. Operations research uses advanced analytical methods to make optimal decisions in order to solve complex problems. The winner of the award will be announced in mid-April 2008. Past Edelman Award finalists include Travelocity; IBM; Merrill Lynch; the Memorial Sloan-Kettering Cancer Center; and Georgia Tech. The winning team for 2007 reduced both patient suffering and health care costs from the treatment of prostate and breast cancer. The Edelman competition attests to the contributions of operations research in the profit and nonprofit sectors. It is estimated that the cumulative dollar benefits from Edelman finalist projects between 1984 and 2006 reached the $100 billion mark. TEVA Research Program The TEVA research program has focused on reducing the security risks to drinking water systems. Ad

  5. Pre-Chemotherapy Differences in Visuospatial Working Memory in Breast Cancer Patients Compared to Controls: An fMRI Study

    PubMed Central

    Scherling, Carole; Collins, Barbara; MacKenzie, Joyce; Bielajew, Catherine; Smith, Andra

    2011-01-01

    Introduction: Cognitive deficits are a side-effect of chemotherapy, however pre-treatment research is limited. This study examines neurofunctional differences during working memory between breast cancer (BC) patients and controls, prior to chemotherapy. Methods: Early stage BC females (23), scanned after surgery but before chemotherapy, were individually matched to non-cancer controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing a Visuospatial N-back task and data was analyzed by multiple group comparisons. fMRI task performance, neuropsychological tests, hospital records, and salivary biomarkers were also collected. Results: There were no significant group differences on neuropsychological tests, estrogen, or cortisol. Patients made significantly fewer commission errors but had less overall correct responses and were slower than controls during the task. Significant group differences were observed for the fMRI data, yet results depended on the type of analysis. BC patients presented with increased activations during working memory compared to controls in areas such as the inferior frontal gyrus, insula, thalamus, and midbrain. Individual group regressions revealed a reverse relationship between brain activity and commission errors. Conclusion: This is the first fMRI investigation to reveal neurophysiological differences during visuospatial working memory between BC patients pre-chemotherapy and controls. These results also increase the knowledge about the effects of BC and related factors on the working memory network. Significance: This highlights the need to better understand the pre-chemotherapy BC patient and the effects of associated confounding variables. PMID:22053153

  6. Subtle hippocampal deformities in breast cancer survivors with reduced episodic memory and self-reported cognitive concerns.

    PubMed

    Apple, Alexandra C; Ryals, Anthony J; Alpert, Kathryn I; Wagner, Lynne I; Shih, Pei-An; Dokucu, Mehmet; Cella, David; Penedo, Frank J; Voss, Joel L; Wang, Lei

    2017-01-01

    Cancer survivors have lingering cognitive problems, however the anatomical basis for these problems has yet to be fully elucidated. Clinical studies as well as animal models of chemotherapy have pinpointed cell and volume loss to the hippocampus, however, few studies have performed shape analysis of the hippocampus on cancer survivors. This study used high-dimensional deformation mapping analysis to test whether localized hippocampal deformation differs in breast cancer survivors who received adjuvant chemotherapy coupled with hormone blockade therapy, and if deformation was related to subjective self-reported concerns and cognitive performance. 3 T MRI images were acquired from 16 pre-menopausal breast cancer survivors and 18 healthy controls without a history of cancer. Breast cancer survivors had undergone chemotherapy within the eighteen months prior to the study, and were receiving estrogen-blockade therapy at the time of the study. Automated high-dimensional deformation mapping was used to compare localized hippocampal deformation differences between groups. Self-reported subjective concerns were assessed using Neuro-QOL Cognitive Function assessment, whereas cognitive performance was evaluated using the NIH Toolbox Cognition Battery. Relative to healthy controls, cancer survivors showed significantly more inward hippocampal deformation, worse self-reported cognitive functioning, and inferior episodic memory test score. This study is the first of its kind to examine the relationship between hippocampal deformity and cognitive impairment in cancer survivors.

  7. 'Do UC the melanoma?' Recognising the importance of different lesions displaying unevenness or having a history of change for early melanoma detection.

    PubMed

    Yagerman, Sarah E; Chen, Lucy; Jaimes, Natalia; Dusza, Stephen W; Halpern, Allan C; Marghoob, Ashfaq

    2014-05-01

    Many melanomas are of a diameter smaller than 6 mm and may lack classical asymmetry, border irregularity and colour variegation (ABCD). The objectives of this article are to characterise the fidelity of melanomas diagnosed in a high-risk clinic to the ABCD and to review potential methods for early clinical detection of melanoma. All cases of primary melanoma diagnosed by one clinician at the Memorial Sloan-Kettering Cancer Center over the past 11 years were evaluated for the presence of the ABCD. The melanomas were analysed for asymmetry of contour, unevenness in distribution of colours and textures, border irregularity, number of colours present and diameter. In all, 236 melanomas were analysed. Of these, asymmetry of contour was present in 65% and 94% demonstrated unevenness in the distribution of colours and textures. The borders were regular in 12% of the melanomas and colour variegation was present in 63%. In total, 28% of the lesions were small, with a diameter less than 6 mm. This study was limited by the subjectivity of clinical lesion analysis. We put forward for your consideration a new mnemonic: 'Do UC (different, uneven, changing) the melanoma?' This mnemonic encompasses differential, analytical and comparative cognition strategies for an enhanced early detection of melanoma. © 2014 The Australasian College of Dermatologists.

  8. Long-term Pulmonary Outcomes in Pediatric Survivors of High-risk Neuroblastoma.

    PubMed

    Stone, Anne; Novetsky Friedman, Danielle; Worgall, Stefan; Kushner, Brian H; Wolden, Suzanne; Modak, Shakeel; LaQuaglia, Michael P; Wu, Xian; Cheung, Nai-Kong; Sklar, Charles A

    2017-10-01

    Children with high-risk neuroblastoma are exposed to multimodality therapies early in life and survivors confront late therapy-related toxicities. This study assessed respiratory symptoms, pulmonary function tests (PFTs), and risk factors for abnormalities among survivors. High-risk neuroblastoma survivors followed in the long-term follow-up clinic at Memorial Sloan Kettering Cancer Center were enrolled. Self-administered symptom questionnaires were completed. Medical records were reviewed for treatment information and comorbidities. PFTs included spirometry, plethysmography, and diffusion capacity of the lung for carbon monoxide (DLCO). Thirty-nine survivors participated (median age at study: 11.4 y; median age at diagnosis: 2.3 y; median time since completion of therapy: 5.5 y). Chronic respiratory symptoms were reported for 33%. PFT abnormalities were identified in 79% and included low forced expiratory volume in 1 second (38%), decreased total lung capacity (44%), and abnormal DLCO (67%). PFT abnormalities were mostly mild to moderate. Mean forced vital capacity, forced expiratory volume in 1 second, and total lung capacity were normal and mean DLCO was mildly abnormal. Risks included thoracic surgery, chest radiation therapy, thoracic surgery plus chest radiation therapy, and shorter time since completion of therapy (P<0.05). Although respiratory abnormalities were common, they were mostly mild or moderate. Continued pulmonary surveillance of this at-risk population is warranted.

  9. Patterns of persistent DNA damage associated with sun exposure and the glutathione S-transferase M1 genotype in melanoma patients.

    PubMed

    Steinberg, Mark L; Hubbard, Karen; Utti, Charles; Clas, Brian; Hwang, Bor-Jang; Hill, Helene Z; Orlow, Irene

    2009-01-01

    Solar radiation can lead to changes affecting DNA metabolism resulting in loss of DNA integrity. Skin specimens obtained from melanoma patients treated at the Memorial Sloan-Kettering Cancer Center were used to study patterns of DNA fragmentation using the comet assay and levels of deletions in mitochondrial DNA (mtDNA) using real-time PCR. Skin specimens were classified according to the glutathione S-transferase M1 (GSTM1) genotype (either wild type [WT] or null) and patient sunburn history. GSTM1 null individuals with a sunburn history showed increased levels of both DNA fragmentation by comet assays and mtDNA deletions relative to GSTM1 WT patients with little or no sunburn history. Microarray analyses identified a number of genes whose expression was upregulated >or=5-fold in cells from GSTM1-null patients or from those reporting histories of sunburn. These genes encoded small molecule transporters, various growth factor/chemokine receptors, transcription factors and tumor suppressors. Of 17 genes directly involved in DNA repair, three DNA ligases were highly upregulated while the RAD23 UV excision repair gene and the Growth Arrest and DNA Damage gene (GADD45) were downregulated. These findings support the idea that exposure to solar radiation early in life may induce long-term cellular changes that lead to persistent DNA damage and altered patterns of gene expression.

  10. Comparison of hepatocellular carcinoma in American and Asian patients by tissue array analysis.

    PubMed

    Song, Tae-Jin; Fong, Yuman; Cho, Sung-Jin; Gönen, Mithat; Hezel, Michael; Tuorto, Scott; Choi, Sang-Yong; Kim, Young-Chul; Suh, Sung-Ock; Koo, Bum-Hwan; Chae, Yang-Seok; Jarnagin, William R; Klimstra, David S

    2012-07-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although some epidemiologic and etiologic differences between Asian and Western HCC are known, detailed comparative studies with pathologic correlations have not been performed. Paraffin sections of resected HCC specimens from Memorial Sloan-Kettering Cancer Center and Korea University Medical Center were used to construct tissue microarrays. Immunohistochemical staining of microarray sections was performed using antibodies against markers of proliferation and regulators of cell cycle. Patient data were correlated with staining results. When comparing both cohorts, significant differences were found in expression of p53 and MDM2. In the Asian group, more frequent positive staining for p53 (24%) was observed compared with the American group (9%; P = 0.037). For MDM2, 26% of American cases stained positive compared with 2% of Asian cases (P = 0.0003). No significant differences were found in expression of Ki67, p21, p27, cyclin D1, or bcl2. Female gender, vascular invasion, and lack of viral hepatitis infection correlated with positive MDM2 staining. These data likely correlate with differences in molecular pathogenesis of HCC based on racial and regional differences. These findings may have implications in choice of molecular targeted therapies based on patient ethnicity. Copyright © 2012 Wiley Periodicals, Inc.

  11. Thinking Critically About Classifying Adverse Events: Incidence of Pancreatitis in Patients Treated With Nivolumab + Ipilimumab.

    PubMed

    Friedman, Claire F; Clark, Varina; Raikhel, Andrew V; Barz, Tim; Shoushtari, Alexander N; Momtaz, Parisa; Callahan, Margaret K; Wolchok, Jedd D; Chapman, Paul B; Hellmann, Matthew D; Postow, Michael A

    2017-04-01

    The Common Terminology Criteria for Adverse Events (CTCAE) were developed to document the adverse effects of chemotherapy but are now also used to document immune-related adverse events (irAE). Characterization of irAE by the CTCAE has implications for determining dose-limiting toxicity (DLT) and, consequently, the recommended phase II dose (RP2D) of investigational agents. In the phase I trial of nivolumab + ipilimumab, an asymptomatic increase in lipase was the primary DLT that informed the RP2D. We performed a retrospective study of 119 patients with melanoma who were treated at Memorial Sloan Kettering Cancer Center with the combination of nivolumab + ipilimumab to investigate the relationship between asymptomatic grade 3 or higher increases in amylase and/or lipase and pancreatitis, a known irAE. Of the 119 patients, there were only two cases of pancreatitis, representing 20% of patients with grade 3 or higher amylase, 6.3% of patients with grade 3 or higher lipase, and 20% of patients with grade 3 or higher elevations of both enzymes. The application of the CTCAE, especially in grading independent lab values, should be considered carefully in clinical trials of novel immunotherapeutic agents. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Nasopharyngeal carcinoma in children: review of 16 cases

    SciTech Connect

    Jereb, B.; Huvos, A.G.; Steinherz, P.; Unal, A.

    1980-04-01

    Of fifty two children with nasopharyngeal tumors who were registered and treated a Memorial Sloan-Kettering Cancer Center (MSKCC), from 1961 through 1977, 16 had carcinoma. The results of retrospective analysis of these patients are presented here. There were 7 girls and 9 boys between 12 and 16 years of age. One patient had a Stage I tumor; one had a Stage II tumor and 14 had Stage IV tumors. The histology was poorly differentiated epidermoid carcinoma in all patients. All patients had radiotherapy to the primary site. Six patients received chemotherapy for distant metastases, and 2 had adjuvant chemotherapy. Of the 13 patients who were treated initially with radiation alone, 2 were alive and free of disease at 12 and 14 years respectively. Of the 3 patients who had chemotherapy at initial treatment, one was alive and free of disease 18 months from diagnosis and one patient died of treatment without tumor. Bone was the common site of distant metastases. While radiation therapy alone appears to be adequate treatment for early tumors, adjuvant chemotherapy should be tried to improve results in advanced tumors.

  13. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    SciTech Connect

    Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

    2013-05-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

  14. The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients.

    PubMed

    Kamboj, Mini; Chung, Dick; Seo, Susan K; Pamer, Eric G; Sepkowitz, Kent A; Jakubowski, Ann A; Papanicolaou, Genovefa

    2010-11-01

    The impact of the rising prevalence of vancomycin-resistant Enterococcus (VRE) prior to hematopoietic stem cell transplantation (HSCT) and changes in transplant techniques on risk of VREB (VRE bacteremia) early after HSCT is not known. This is a retrospective study of 247 adult patients who underwent allogeneic HSCT in the years 2008 and 2009 at the Memorial Sloan-Kettering Cancer Center. Sixty-eight of 247 (27.5%) patients were VRE colonized on pretransplant screening. VRE was the leading cause of bacteremia in the first 30 days after HSCT; 23 of 43 (53.5%) patients with positive blood cultures had VRE. Only 13 (57%) of the 23 patients with early VREB were colonized with VRE on pre-HSCT screening cultures. Mortality was directly attributable to VRE infection in 9% of patients with early VREB. VRE is emerging as the most common cause of preengraftment bacteremia in patients undergoing allogeneic HSCT, and is associated with substantial mortality. Pre-HSCT screening for VRE with stool cultures will not identify all patients who are at risk for VREB. The use of alternate agents with activity against Gram-positive bacteria for fever and neutropenia early after HSCT should be evaluated further in prospective studies. Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. The Changing Epidemiology of Vancomycin-Resistant Enterococcus (VRE) Bacteremia in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients

    PubMed Central

    Kamboj, Mini; Chung, Dick; Seo, Susan K.; Pamer, Eric G.; Sepkowitz, Kent A.; Jakubowski, Ann A.; Papanicolaou, Genovefa

    2013-01-01

    The impact of the rising prevalence of vancomycin-resistant Enterococcus (VRE) prior to hematopoietic stem cell transplantation (HSCT) and changes in transplant techniques on risk of VREB (VRE bacteremia) early after HSCT is not known. This is a retrospective study of 247 adult patients who underwent allogeneic HSCT in the years 2008 and 2009 at the Memorial Sloan-Kettering Cancer Center. Sixty-eight of 247 (27.5%) patients were VRE colonized on pretransplant screening. VRE was the leading cause of bacteremia in the first 30 days after HSCT; 23 of 43 (53.5%) patients with positive blood cultures had VRE. Only 13 (57%) of the 23 patients with early VREB were colonized with VRE on pre-HSCT screening cultures. Mortality was directly attributable to VRE infection in 9% of patients with early VREB. VRE is emerging as the most common cause of preengraftment bacteremia in patients undergoing allogeneic HSCT, and is associated with substantial mortality. Pre-HSCT screening for VRE with stool cultures will not identify all patients who are at risk for VREB. The use of alternate agents with activity against Gram-positive bacteria for fever and neutropenia early after HSCT should be evaluated further in prospective studies. PMID:20685257

  16. An interview with Hakim Djaballah, Ph.D. Interview by Vicki Glaser.

    PubMed

    Djaballah, Hakim

    2010-10-01

    Dr. Hakim Djaballah is Director of the High-Throughput Screening (HTS) Core Facility at Memorial Sloan-Kettering Cancer Center (MSKCC), in New York City. He has several years of industrial experience in preclinical drug discovery, working in both pharmaceutical and biotechnology companies. He has been involved in developing and screening antibacterials, antivirals, and antifungals, as well as identifying targets in various therapeutic areas, including diabetes, central nervous system, cardiovascular system, oncology, and inflammation. He obtained his B.S. in biochemistry with biotechnology from the University of Birmingham and completed his Ph.D. in biochemistry at the University of Leicester, both in England. He was recruited to MSKCC in 2003 to set up and direct the HTS Core Facility, a drug discovery laboratory involved in both chemical and RNAi screening. Dr. Djaballah was the recipient of the 2007 Robots and Vision User Recognition Award. Sponsored by the Robotic Industries Association and the Automated Imaging Association, the award is presented every 2 years to individuals in institutions that have successfully implemented robots in their work.

  17. Implanted Cardiac Defibrillator Care in Radiation Oncology Patient Population

    SciTech Connect

    Gelblum, Daphna Y. Amols, Howard

    2009-04-01

    Purpose: To review the experience of a large cancer center with radiotherapy (RT) patients bearing implantable cardiac defibrillators (ICDs) to propose some preliminary care guidelines as we learn more about the devices and their interaction with the therapeutic radiation environment. Methods and Materials: We collected data on patients with implanted ICDs treated with RT during a 2.5-year period at any of the five Memorial Sloan-Kettering clinical campuses. Information regarding the model, location, and dose detected from the device, as well as the treatment fields, fraction size, and treatment energy was collected. During this time, a new management policy for these patients had been implemented requiring treatment with low-energy beams (6 MV) and close surveillance of the patients in partnership with their electrophysiologist, as they received RT. Results: During the study period, 33 patients were treated with an ICD in place. One patient experienced a default of the device to its initial factory setting that was detected by the patient hearing an auditory signal from the device. This patient had initially been treated with a 15-MV beam. After this episode, his treatment was replanned to be completed with 6-MV photons, and he experienced no further events. Conclusion: Patients with ICDs and other implanted computer-controlled devices will be encountered more frequently in the RT department, and proper management is important. We present a policy for the safe treatment of these patients in the radiation oncology environment.

  18. Approaches to Manufacturing Alpha Emitters For Radioimmunotherapeutic Drugs

    SciTech Connect

    Gaylord King, A.; Givens, Kenneth R.; Miller, William H.; Glascock, Mike; Rangaraj, Dharanipathy; Bond, Andrew; Horwitz, E. Philip; McAlister, Daniel R.

    2003-08-26

    Several alpha emitting isotopes have been proposed for radioimmunotherapy. To produce these nuclides reliably and in quantities needed, unique manufacturing approaches will be required. This paper describes the approaches that are being developed for the manufacture of 225Actinium (225 Ac) that decays to 213Bismuth (213 Bi) and the commercial manufacturing approaches. Oak Ridge National Laboratory (ORNL) currently supplies the actinium used for research and medical use. Today the ORNL 233U stockpiles only provide sufficient material for research quantities of 213 Bi. At the Institute for Transuranium Elements (ITU), in Karlsruhe, researchers have also developed a method of irradiating radium-226 with protons in a cyclotron to produce actinium- 225 through the reaction 226Ra (p, 2n) 225Ac. Researchers from the Missouri University (MU), the Missouri University Research Reactor (MURR), MedActinium, Inc. and Los Alamos National Laboratory (LANL) are working on a collaborative effort to benchmark and optimize the production of 213Bi via neutron bombardment of 226Ra. MedActinium, Inc., in collaboration with commercial and institutional investigators at PG Research Foundation (PGRF) and Memorial Sloan Kettering Cancer Center (MSKCC), is developing commercial approaches to manufacturing these unique radioimmunotherapeutic drugs.

  19. Primary Ewing Family of Tumors of the Jaw has a better Prognosis compared to Tumors of Extragnathic sites

    PubMed Central

    Owosho, Adepitan A.; Ko, Eugene; Rosenberg, Haley I.; Yom, SaeHee K.; Antonescu, Cristina R.; Huryn, Joseph M.; Estilo, Cherry L.

    2016-01-01

    Purpose Primary Ewing sarcoma of the jaw is rare. The aim of this study was to describe new cases of primary Ewing sarcoma of the jaw and investigate reported prognostic factors of Ewing sarcoma in this series and treatment outcome. Materials and Methods Six patients with primary Ewing sarcoma of the jaw were treated at the Memorial Sloan Kettering Cancer Center (MSKCC) from 1992 through 2013. Clinical data, pathology reports, treatment prescribed, treatment regimens, outcome, and follow-up information were reviewed. Results Five of 6 patients were female and 5 cases were in the mandible. No patient presented with metastatic disease at diagnosis. All cases were positive for CD99, and 3 patients with genetic confirmation were positive for EWS-FLI1 fusion or EWSR1 gene rearrangement. All patients received induction multiagent chemotherapy and surgical resection and 2 patients received adjuvant radiotherapy. Total (grade IV) or nearly total (grade III) tumor necrosis in 3 of 5 patients (60%) assessed for histologic response to chemotherapy indicated intense sensitivity. All patients were alive and free of disease, with no history of local recurrence, at a median follow-up period of 6.5 years. Conclusion Patients with primary Ewing sarcoma of the jaw have a good prognosis and metastasis is an uncommon occurrence at initial presentation. PMID:26679553

  20. NOTE: Optimal needle arrangement for intraoperative planning in permanent I-125 prostate implants

    NASA Astrophysics Data System (ADS)

    Thompson, S. A.; Fung, A. Y. C.; Zaider, M.

    2002-08-01

    One limitation of intraoperative planning of permanent prostate implants is that needles must already be in the gland before planning images are acquired. Improperly placed needles often restrict the capability of generating optimal seed placement. We developed guiding principles for the proper layout of needles within the treatment volume. The Memorial Sloan-Kettering Cancer Center planning system employs a genetic algorithm to find the optimal seed implantation pattern consistent with pre-assigned constraints (needle geometry, uniformity, conformity and the avoidance of high doses to urethra and rectum). Ultrasound volumes for twelve patients with I-125 implants were used to generate six plans per patient (total 72 plans) with different needle arrangements. The plans were evaluated in terms of V100 (percentage prostate volume receiving at least the prescription dose), U135 (percentage urethra volume receiving at least 135% of prescription dose), and CI (conformity index, the ratio of treatment volume to prescription dose volume.) The method termed POSTCTR, in which needles were placed on the periphery of the largest ultrasound slice and posterior central needles were placed as needed, consistently gave superior results for all prostate sizes. Another arrangement, labelled POSTLAT, where the needles were placed peripherally with additional needles in the posterior lateral lobes, also gave satisfactory results. We advocate two needle arrangements, POSTCTR and POSTLAT, with the former giving better results.

  1. Intraluminal radiation therapy in the management of malignant biliary obstruction

    SciTech Connect

    Molt, P.; Hopfan, S.; Watson, R.C.; Botet, J.F.; Brennan, M.F.

    1986-02-01

    Fifteen patients with malignant biliary obstruction from carcinoma of the bile ducts, gallbladder, and pancreas (Group I) or metastatic disease (Group II) were treated with intraluminal radiation therapy (ILRT) at Memorial Sloan-Kettering Cancer Center. In 11 cases ILRT was used as a central boost in combination with 3000 cGy external beam radiation therapy (ERT). No significant treatment toxicity was observed. Cholangiographic response was observed in 2 of 12 evaluable patients. In no patient was long-term relief of jaundice without indwelling biliary stent achieved. Survival from treatment in eight Group I patients treated with ILRT +/- ERT was 3 to 13 months (median, 4.5). Survival in seven similarly treated Group II patients was 0.5 to 8 months (median, 4.0). Additional data for ten similar patients referred for ILRT but treated with ERT alone are presented. Analysis of this and other reports indicate the need for prospective controlled trials of the role of this regimen in the management of malignant biliary obstruction before wider application can be recommended.

  2. Meeting report: fourth international congress of the Society for Melanoma Research.

    PubMed

    Fisher, David E; Medrano, Estela E; McMahon, Martin; Soengas, Marisol S; Schuchter, Lynn; Wolchok, Jedd D; Merlino, Glenn

    2008-02-01

    The 4th international melanoma congress of the Society for Melanoma Research (SMR), organized by Marianne Berwick (University of New Mexico), Paul Chapman (Memorial Sloan-Kettering Cancer Center), Rene Gonzalez (University of Colorado) and Ze'ev Ronai (Burnham Institute), was held at the Marriott Hotel in downtown New York on November 2007. The congress was attended by a record high number of attendees (over 500 delegates) who joined to discuss recent advances in melanoma biology and therapy. About 40% of the participants arrived from 39 countries, a testament to the high impact of this annual gathering on the international melanoma community. Over 120 of the participants were students or postdoctoral fellows, representing a most impressive fraction of young scientists engaged in melanoma research. The meeting consisted of more than 50 plenary and minisymposia presentations, stimulating the exchange of unpublished data and novel ideas, and helping to forge new collaborations that are anticipated to facilitate significant advances in basic, translational and clinical melanoma research. Another major focus of this meeting was over 160 posters, which were heavily attended and provided an effective forum for extensive informal discussions. This report will highlight the major scientific themes and advances of this most successful meeting, and provide a useful perspective on the current state of melanoma research, as well as where the field should be heading.

  3. A weekly regimen with dose escalation of doxorubicin for patients with advanced Hodgkin's lymphoma: results of a phase II study of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA).

    PubMed

    Fermé, Christophe; Brice, Pauline; Michallet, Anne-Sophie; Lederlin, Pierre; Diviné, Marine; Casasnovas, Olivier; Devidas, Alain; Anglaret, Bruno; Cazals-Hatem, Dominique; Mounier, Nicolas

    2007-04-01

    This multicenter phase II study assessed the feasibility and efficacy of a weekly chemotherapy regimen with a moderately escalated dose of doxorubicin administered over 16 weeks, followed by radiation therapy (RT) to bulky sites. From July 1996 to February 1998, 44 untreated patients with stage IIIB-IV Hodgkin's lymphoma (HL), and 0 - 2 risk factors described by the Memorial Sloan-Kettering Cancer Center, were treated. Chemotherapy was a combination of increased-dose doxorubicin with conventional doses of cyclophosphamide, vinblastine, prednisone, vindesine, bleomycin, and etoposide. Patients received four cycles of the weekly regimen for 16 weeks. Forty-one patients received the planned four cycles of chemotherapy, and RT was delivered to 36 patients. The incidence of WHO grade 3 - 4 neutropenia was 90%. A total of 39 patients achieved a complete remission (88.6%). The median follow-up was 95 months. The 7-years freedom from treatment failure and overall survival estimates were 57% (95% confidence interval (CI), 41% - 70%), and 93% (95% CI, 80 - 98%), respectively. The relapse rate was related to the short duration of chemotherapy, and the failure to prevent relapses with consolidation RT. In this study population the 16-week regimen and RT to bulky sites were not sufficient for disease control.

  4. Intracranial meningioma with vertebral or intraspinal metastasis: report of 2 cases and review of the literature.

    PubMed

    Singh, Ranjodh; Ryan, Christopher; Chohan, Muhammad O; Tisnado, Jamie; Hadjigeorgiou, Georgios F; Bilsky, Mark H

    2016-12-01

    Extracranial meningioma metastases (EMM) occur in 0.1% of intracranial meningioma patients and are more commonly seen in those with atypical and anaplastic histologies. While the lungs and pleura are the most common site of EMM, intraspinal and vertebral EMM also occur and are not well described in the literature. Although the presence of EMM can worsen prognosis, no standard of care has been established for EMM management. All patients treated for recurrent atypical/anaplastic meningiomas between January 1985 and July 2014 at Memorial Sloan Kettering Cancer Center were screened for intraspinal and vertebral EMM. Of these patients, 2 were identified as having recurrent meningioma complicated by vertebral or intraspinal EMM. A review of the literature was also conducted. The PubMed database was screened for intraspinal and vertebral EMM cases reported in the literature from 1985 to 2015. Nineteen articles were identified from the literature and included 24 individual cases with a total of 34 vertebral or intraspinal EMM. Forty-two percent (10/24) of patients with vertebral or intraspinal EMM had WHO Grade I tumors. Furthermore, 25% (6/24) of vertebral and intraspinal EMM occurred after the primary tumor but prior to any recurrence. This paper highlights that vertebral and intraspinal EMM can occur in patients with WHO Grade I meningiomas and can occur before tumor recurrence. This challenges the notion that EMM are seen primarily in high-grade atypical and anaplastic meningiomas.

  5. Broad-spectrum multi-modality image registration: from PET, CT, and MRI to autoradiography, microscopy, and beyond.

    PubMed

    Zanzonico, P B

    2006-01-01

    Image registration and fusion are increasingly important components of both clinical and small-animal imaging and have lead to the development of a variety of pertinent hardware and software tools, including multi-modality, e.g. PET-CT, devices. At the same time, advances in microscopic imaging, including phosphor-plate digital autoradiography and immunohistochemistry, now allow ultra-high (sub-100 microm)-resolution molecular characterization of tissue sections. To date, however, in vivo imaging of intact subjects and ex vivo imaging of harvested tissues sections have remained separate and distinct, making it difficult to reliably inter-compare the former and the latter. The Department of Medical Physics and the Radiation Biophysics Laboratory at Memorial Sloan-Kettering Cancer Center, under the direction of Dr. Clifton Ling, has now designed, fabricated, and tested a stereotactic imaging system for so-called "broad-spectrum" image registration, from coarser-resolution in vivo imaging modalities such as PET, CT, and MRI to ultra-high-resolution ex vivo imaging techniques such as histology, autoradiography, and immunohistochemistry.

  6. Genetic analysis of a morphologically heterogeneous ovarian endometrioid carcinoma.

    PubMed

    Geyer, Felipe C; Pareja, Fresia; Burke, Kathleen A; Schultheis, Anne M; Hussein, Yaser R; Ye, Jiqing; De Filippo, Maria R; Marchio, Caterina; Macedo, Gabriel S; Piscuoglio, Salvatore; Lim, Raymond S; Toy, Eugene; Murali, Rajmohan; Jungbluth, Achim A; Reis-Filho, Jorge S; Soslow, Robert A; Weigelt, Britta

    2017-09-01

    Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally related to and originate from the low-grade endometrioid carcinoma remains unclear. The aim of this study was to use massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low-grade and high-grade components. DNA samples extracted from each tumour component (low-grade endometrioid, high-grade anaplastic and high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing with the 410-gene Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay. Somatic single nucleotide variants, small insertions and deletions, and copy number alterations were detected with state-of-the-art bioinformatics algorithms, and validated with orthogonal methods. The endometrioid carcinoma and the associated high-grade components shared copy number alterations and four clonal mutations, including SMARCA4 mutations, which resulted in loss of BRG1 protein expression. Subclonal mutations and mutations restricted to single components were also identified, such as distinct TP53 mutations restricted to each histological component. Histologically distinct components of ovarian endometrioid carcinomas may show intratumour genetic heterogeneity but be clonally related, harbouring a complex clonal composition. In the present case, SMARCA4 mutations were probably early events, whereas TP53 somatic mutations were acquired later in evolution. © 2017 John Wiley & Sons Ltd.

  7. Post-operative hemimaxillectomy rehabilitation using prostheses supported by zygoma implants and remaining natural teeth

    PubMed Central

    Qu, Xing Zhou; Wang, Ming Yi; Ong, Hui Shan; Zhang, Chen Ping

    2016-01-01

    OBJECTIVES: This study aimed to evaluate the stability of prostheses supported by zygoma implants and remaining teeth for subjects who had undergone hemi-maxillectomy. METHODS: Ten patients were included in the study. Oral rehabilitation was performed using a temporary prosthesis that was supported by remaining teeth for the first three months. Then, a zygoma implant was placed to provide support for a final prosthesis in addition to the remaining teeth. Each prosthesis was tailor-made according to biomechanical three-dimensional finite element analysis results. The patients were assessed using the prosthesis functioning scale of the Memorial Sloan-Kettering Cancer Center. In addition, retention and bite force were recorded for both the temporary prosthesis and the final prosthesis. RESULTS: The mean bite force of the prosthetic first molar was increased to 69.2 N. The mean retentive force increased to 13.5 N after zygoma implant insertion. The bite force on the prosthetic first molar was improved to 229.3 N. CONCLUSION: Bite force increased significantly with the support of a zygoma implant. The use of zygoma implants in the restoration of maxillary defects improved functional outcome and patient satisfaction. PMID:27759845

  8. Cancer-reactive memory T cells from bone marrow: Spontaneous induction and therapeutic potential (Review).

    PubMed

    Schirrmacher, Volker

    2015-12-01

    Cognate interactions between naïve tumor antigen (TA)-specific T cells and TA-presenting dendritic cells (DCs) are facilitated by secondary lymphoid organs such as lymph nodes or the spleen. These can result either in TA-specific tolerance or, depending on environmental costimulatory signals, in TA-specific immune responses. In the present review, we describe such events for the bone marrow (BM) when blood-borne TA, released from the primary tumor or expressed by blood circulating tumor cells or DCs enters the BM stroma and parenchyma. We argue that cognate T-DC interactions in the BM result in immune responses and generation of memory T cells (MTCs) rather than tolerance because T cells in the BM show an increased level of pre-activation. The review starts with the spontaneous induction of cancer-reactive MTCs in the BM and the involvement of such MTCs in the control of tumor dormancy. The main part deals with the therapeutic potency of BM MTCs. This is a new area of research in which the authors research group has performed pioneering studies which are summarized. These include studies in animal tumor models, studies with human cells in tumor xenotransplant models and clinical studies. Based on observations of an enormous expansion capacity, longevity and therapeutic capacity of BM MTCs, a hypothesis is presented which suggests the involvement of stem-like MTCs.

  9. An Associative Memory Model for Integration of Fragmented Research Data and Identification of Treatment Correlations in Breast Cancer Care

    PubMed Central

    Banerjee, Ashis Gopal; Khan, Mridul; Higgins, John; Giani, Annarita; Das, Amar K.

    2015-01-01

    A major challenge in advancing scientific discoveries using data-driven clinical research is the fragmentation of relevant data among multiple information systems. This fragmentation requires significant data-engineering work before correlations can be found among data attributes in multiple systems. In this paper, we focus on integrating information on breast cancer care, and present a novel computational approach to identify correlations between administered drugs captured in an electronic medical records and biological factors obtained from a tumor registry through rapid data aggregation and analysis. We use an associative memory (AM) model to encode all existing associations among the data attributes from both systems in a high-dimensional vector space. The AM model stores highly associated data items in neighboring memory locations to enable efficient querying operations. The results of applying AM to a set of integrated data on tumor markers and drug administrations discovered anomalies between clinical recommendations and derived associations. PMID:26958161

  10. A pilot study to compare the effect of memory training and health training interventions on affective and cognitive function with a group of cancer survivors

    PubMed Central

    McDougall, Graham J.; Becker, Heather; Acee, Taylor W.; Vaughan, Phillip W.; Delville, Carol L.

    2010-01-01

    Cancer survivors over 65 years of age experience treatment-induced memory impairments. However, clinicians are often at a loss on how to intervene for these cognitive problems. This paper describes the findings from a pilot study of a memory vs. health training intervention and its adaptability for cancer survivors. Design and Methods A convenience sample of older adults was enrolled in a longitudinal study of a memory and health training intervention and tested on five occasions for 2 years post-intervention. The memory training was designed to reduce anxiety, decrease negative attributions, promote health, and increase self-efficacy. In this analysis we included change over time for the first four of the five data collection points. We calculated means and standard deviations on the memory measures for cancer survivors in the intervention (n=8) and comparison (n=14) groups. The analysis consisted of a mixed design ANOVA comparing the two intervention groups across 4 time periods for twelve months. Results The typical cancer survivor in the sample was a 74-year old Caucasian female; 14% were minorities. Because of the small sample, some of the effects were not statistically significant. Moderate to large effects were revealed in everyday and verbal memory performance scores, memory self-efficacy, strategy use, and memory complaints. There were also moderate effects for group by time interactions on the visual memory performance measure, the memory self-efficacy measure, the depression, the trait anxiety measure, and the complaints subscale. The memory intervention group tended to improve more than the health training group, although this was not always consistent. The results suggested that the participants benefited from the memory training intervention. Implications Clinicians are often at a loss on how to intervene with cancer survivors who are experiencing cognitive problems following chemotherapy treatment. Evidenced-based interventions for this aspect of

  11. Delirium in advanced age and dementia: A prolonged refractory course of delirium and lower functional status.

    PubMed

    Boettger, Soenke; Jenewein, Josef; Breitbart, William

    2015-08-01

    The factors associated with persistent delirium, in contrast to resolved delirium, have not been studied well. The aim of our present study was to identify the factors associated with delirium resolution as measured by the Memorial Delirium Assessment Scale (MDAS) and functional improvement as measured by the Karnofsky Performance Status (KPS) scale. All subjects were recruited from psychiatric referrals at the Memorial Sloan Kettering Cancer Center (MSKCC). The two study instruments were performed at baseline (T1), at 2-3 days (T2), and at 4-7 days (T3). Subjects with persistent delirium were compared to those with resolved delirium in respect to sociodemographic and medical variables. Overall, 26 out of 111 patients had persistent delirium. These patients were older, predominantly male, and had more frequently preexisting comorbid dementia. Among cancer diagnoses and stage of illness, brain cancer and terminal illness contributed to persistent delirium or late response, whereas gastrointestinal cancer was associated with resolved delirium. Among etiologies, infection responded late to delirium management, usually at one week. Furthermore, delirium was more severe in patients with persistent delirium from baseline through one week. At baseline, MDAS scores were 20.1 in persistent delirium compared to 17 to 18.8 in resolved delirium (T2 and T3), and at one week of management (T3), MDAS scores were 15.2 and 4.7 to 7.4, respectively. At one week of management, persistent delirium manifested in more severe impairment in the domains of consciousness, cognition, organization, perception, psychomotor behavior, and sleep-wake cycle. In addition, persistent delirium caused more severe functional impairment. In this delirium sample, advanced age and preexisting dementia, as well as brain cancer, terminal illness, infection, and delirium severity contributed to persistent delirium or late response, indicating a prolonged and refractory course of delirium, in addition to more

  12. Delirium in advanced age and dementia: A prolonged refractory course of delirium and lower functional status

    PubMed Central

    BOETTGER, SOENKE; JENEWEIN, JOSEF; BREITBART, WILLIAM

    2017-01-01

    Objective The factors associated with persistent delirium, in contrast to resolved delirium, have not been studied well. The aim of our present study was to identify the factors associated with delirium resolution as measured by the Memorial Delirium Assessment Scale (MDAS) and functional improvement as measured by the Karnofsky Performance Status (KPS) scale. Method All subjects were recruited from psychiatric referrals at the Memorial Sloan Kettering Cancer Center (MSKCC). The two study instruments were performed at baseline (T1), at 2–3 days (T2), and at 4–7 days (T3). Subjects with persistent delirium were compared to those with resolved delirium in respect to sociodemographic and medical variables. Results Overall, 26 out of 111 patients had persistent delirium. These patients were older, predominantly male, and had more frequently preexisting comorbid dementia. Among cancer diagnoses and stage of illness, brain cancer and terminal illness contributed to persistent delirium or late response, whereas gastrointestinal cancer was associated with resolved delirium. Among etiologies, infection responded late to delirium management, usually at one week. Furthermore, delirium was more severe in patients with persistent delirium from baseline through one week. At baseline, MDAS scores were 20.1 in persistent delirium compared to 17 to 18.8 in resolved delirium (T2 and T3), and at one week of management (T3), MDAS scores were 15.2 and 4.7 to 7.4, respectively. At one week of management, persistent delirium manifested in more severe impairment in the domains of consciousness, cognition, organization, perception, psychomotor behavior, and sleep–wake cycle. In addition, persistent delirium caused more severe functional impairment. Significance of results In this delirium sample, advanced age and preexisting dementia, as well as brain cancer, terminal illness, infection, and delirium severity contributed to persistent delirium or late response, indicating a prolonged

  13. Impact of increasing physical activity on cognitive functioning in breast cancer survivors: Rationale and study design of Memory & Motion

    PubMed Central

    Hartman, Sheri J.; Natarajan, Loki; Palmer, Barton W.; Parker, Barbara; Patterson, Ruth E.; Sears, Dorothy D.

    2015-01-01

    Introduction Many breast cancer survivors experiences problems with cognitive functioning that can persist years after treatment. Increasing physical activity has been shown to improve cognitive functioning in healthy and cognitively impaired adults, but has not yet been tested in cancer survivors. The primary aim of this randomized controlled trial is to examine the effects of a 3-month physical activity intervention compared to a waitlist control arm on neuropsychological outcomes and subjective cognitive concerns in breast cancer survivors. Methods Eighty sedentary breast cancer survivors, self-reporting difficulties with cognition, will be randomized into an Exercise arm or Control arm. The Exercise arm includes an activity tracker (i.e., a Fitbit), phone calls, plus tailored and non-tailored email content. The Control arm will receive emails on women’s health topics on the same schedule as the Exercise arm. Assessments conducted at baseline and 3 months include: neuropsychological testing, cognitive concerns and other aspects of quality of life, and 7 days of a hip-worn accelerometer. Participants will also provide fasting blood draws to assess brain-derived neurotropic factor, Insulin-like growth factor 1, insulin resistance, and C-reactive protein. Primary and secondary outcomes are changes in neuropsychological testing and cognitive concerns. Biomarkers will be examined to further understand the underlying relationship between physical activity and cognition. Conclusion The Memory & Motion study is designed to test whether increasing physical activity can improve cognitive functioning in breast cancer survivors. Results from this study could be used to guide development of interventions to improve cognitive functioning in breast cancer survivors. PMID:26427563

  14. A conversation with Susan Band Horwitz.

    PubMed

    Horwitz, Susan Band; Goldman, I David

    2015-01-01

    Susan Band Horwitz is a Distinguished Professor and holds the Falkenstein Chair in Cancer Research at Albert Einstein College of Medicine in New York. She is co-chair of the Department of Molecular Pharmacology and associate director for therapeutics at the Albert Einstein Cancer Center. After graduating from Bryn Mawr College, Dr. Horwitz received her PhD in biochemistry from Brandeis University. She has had a continuing interest in natural products as a source of new drugs for the treatment of cancer. Her most seminal research contribution has been in the development of Taxol(®). Dr. Horwitz and her colleagues made the discovery that Taxol had a unique mechanism of action and suggested that it was a prototype for a new class of antitumor drugs. Although Taxol was an antimitotic agent blocking cells in the metaphase stage of the cell cycle, Dr. Horwitz recognized that Taxol was blocking mitosis in a way different from that of other known agents. Her group demonstrated that the binding site for Taxol was on the β-tubulin subunit. The interaction of Taxol with the β-tubulin subunit resulted in stabilized microtubules, essentially paralyzing the cytoskeleton, thereby preventing cell division. Dr. Horwitz served as president (2002-2003) of the American Association for Cancer Research (AACR). She is a member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. She has received numerous honors and awards, including the C. Chester Stock Award from Memorial Sloan Kettering Cancer Center, the Warren Alpert Foundation Prize from Harvard Medical School, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society's Medal of Honor, and the AACR Award for Lifetime Achievement in Cancer Research. The following interview was conducted on January 23, 2014.

  15. Learning and memory performance in breast cancer survivors 2 to 6 years post-treatment: the role of encoding versus forgetting.

    PubMed

    Root, James C; Andreotti, Charissa; Tsu, Loretta; Ellmore, Timothy M; Ahles, Tim A

    2016-06-01

    Our previous retrospective analysis of clinically referred breast cancer survivors' performance on learning and memory measures found a primary weakness in initial encoding of information into working memory with intact retention and recall of this same information at a delay. This suggests that survivors may misinterpret cognitive lapses as being due to forgetting when, in actuality, they were not able to properly encode this information at the time of initial exposure. Our objective in this study was to replicate and extend this pattern of performance to a research sample to increase the generalizability of this finding in a sample in which subjects were not clinically referred for cognitive issues. We contrasted learning and memory performance between breast cancer survivors on endocrine therapy 2 to 6 years post-treatment with age- and education-matched healthy controls. We then stratified lower- and higher-performing breast cancer survivors to examine specific patterns of learning and memory performance. Contrasts were generated for four aggregate visual and verbal memory variables from the California Verbal Learning Test-2 (CVLT-2) and the Brown Location Test (BLT): Single-trial Learning: Trial 1 performance, Multiple-trial Learning: Trial 5 performance, Delayed Recall: Long-delay Recall performance, and Memory Errors: False-positive errors. As predicted, breast cancer survivors' performance as a whole was significantly lower on Single-trial Learning than the healthy control group but exhibited no significant difference in Delayed Recall. In the secondary analysis contrasting lower- and higher-performing survivors on cognitive measures, the same pattern of lower Single-trial Learning performance was exhibited in both groups, with the additional finding of significantly weaker Multiple-trial Learning performance in the lower-performing breast cancer group and intact Delayed Recall performance in both groups. As with our earlier finding of weaker initial

  16. The Hospital for the Ruptured and Crippled: William Bradley Coley, Third Surgeon-in-Chief 1925–1933

    PubMed Central

    2007-01-01

    In January 1925, the Board of Managers of the New York Society for the Relief of the Ruptured and Crippled appointed William Bradley Coley, M.D., age 63, Surgeon-in-Chief of the Hospital for the Ruptured and Crippled (R & C) to succeed Virgil P. Gibney who submitted his resignation the month before. It would be the first time a general surgeon held that position at the oldest orthopedic hospital in the nation, now known as Hospital for Special Surgery (HSS). Coley had been on staff for 36 years and was world famous for introducing use of toxins to treat malignant tumors, particularly sarcomas. A graduate of Yale College and Harvard Medical College, Coley interned at New York Hospital and was appointed, soon after, to the staff of the New York Cancer Hospital (now Memorial Sloan Kettering Cancer Center) located at that time at 106th Street on the West Side of New York. With his mentor Dr. William Bull, Coley perfected the surgical treatment of hernias at R & C. He was instrumental in raising funds for his alma maters, Yale, Harvard and Memorial Hospital. His crusade in immunology as a method of treatment for malignant tumors later fell out of acceptance in the medical establishment. After his death in 1936, an attempt to revive interest in use of immunotherapy for inoperable malignancies was carried out by his daughter, Helen Coley Nauts, who pursued this objective until her death at age 93 in 2000. Coley’s health deteriorated in his later years, and in 1933, he resigned as chief of Bone Tumors at Memorial Hospital and Surgeon-in-Chief at R & C, being succeeded at Ruptured and Crippled as Surgeon-in-Chief by Dr. Eugene H. Pool. William Bradley Coley died of intestinal infarction in 1936 and was buried in Sharon, Connecticut. PMID:18751855

  17. Delirium and severe illness: Etiologies, severity of delirium and phenomenological differences.

    PubMed

    Boettger, Soenke; Jenewein, Josef; Breitbart, William

    2015-08-01

    Our aim was to examine the characteristics of delirium in the severely medically ill cancer population on the basis of sociodemographic and medical variables, delirium severity, and phenomenology, as well as severity of medical illness. All subjects in the database were recruited from psychiatric referrals at Memorial Sloan Kettering Cancer Center (MSKCC). Sociodemographic and medical variables, as well as the Karnofsky Performance Status (KPS) scale and Memorial Delirium Assessment Scale (MDAS) scores were recorded at baseline. Subsequently, these variables were analyzed with respect to the severity of the medical illness. Out of 111 patients, 67 qualified as severely medically ill. KPS scores were 19.7 and 30.7 in less severe illness. There were no significant differences with respect to age, history of dementia, and MDAS scores. Although the severity of delirium did not differ, an increased frequency and severity of consciousness disturbance, disorientation, and inability to maintain and shift attention did exist. With respect to etiologies contributing to delirium, hypoxia and infection were commonly associated with severe illness. In contrast, corticosteroid administration was more often associated with less severe illness. There were no differences with respect to opiate administration, dehydration, and CNS disease, including brain metastasis. Delirium in the severely medically ill cancer population has been characterized by an increased disturbance of consciousness, disorientation, and an inability to maintain and shift attention. However, the severity of illness did not predict severity of delirium. Furthermore, hypoxia and infection were etiologies more commonly associated with delirium in severe illness, whereas the administration of corticosteroids was associated with less severe illness.

  18. Delirium and severe illness: Etiologies, severity of delirium and phenomenological differences

    PubMed Central

    BOETTGER, SOENKE; JENEWEIN, JOSEF; BREITBART, WILLIAM

    2017-01-01

    Objective Our aim was to examine the characteristics of delirium in the severely medically ill cancer population on the basis of sociodemographic and medical variables, delirium severity, and phenomenology, as well as severity of medical illness. Method All subjects in the database were recruited from psychiatric referrals at Memorial Sloan Kettering Cancer Center (MSKCC). Sociodemographic and medical variables, as well as the Karnofsky Performance Status (KPS) scale and Memorial Delirium Assessment Scale (MDAS) scores were recorded at baseline. Subsequently, these variables were analyzed with respect to the severity of the medical illness. Results Out of 111 patients, 67 qualified as severely medically ill. KPS scores were 19.7 and 30.7 in less severe illness. There were no significant differences with respect to age, history of dementia, and MDAS scores. Although the severity of delirium did not differ, an increased frequency and severity of consciousness disturbance, disorientation, and inability to maintain and shift attention did exist. With respect to etiologies contributing to delirium, hypoxia and infection were commonly associated with severe illness. In contrast, corticosteroid administration was more often associated with less severe illness. There were no differences with respect to opiate administration, dehydration, and CNS disease, including brain metastasis. Significance of Results Delirium in the severely medically ill cancer population has been characterized by an increased disturbance of consciousness, disorientation, and an inability to maintain and shift attention. However, the severity of illness did not predict severity of delirium. Furthermore, hypoxia and infection were etiologies more commonly associated with delirium in severe illness, whereas the administration of corticosteroids was associated with less severe illness. PMID:25191904

  19. Test-retest reliability of Brazilian version of Memorial Symptom Assessment Scale for assessing symptoms in cancer patients.

    PubMed

    Menezes, Josiane Roberta de; Luvisaro, Bianca Maria Oliveira; Rodrigues, Claudia Fernandes; Muzi, Camila Drumond; Guimarães, Raphael Mendonça

    2017-01-01

    To assess the test-retest reliability of the Memorial Symptom Assessment Scale translated and culturally adapted into Brazilian Portuguese. The scale was applied in an interview format for 190 patients with various cancers type hospitalized in clinical and surgical sectors of the Instituto Nacional de Câncer José de Alencar Gomes da Silva and reapplied in 58 patients. Data from the test-retest were double typed into a Microsoft Excel spreadsheet and analyzed by the weighted Kappa. The reliability of the scale was satisfactory in test-retest. The weighted Kappa values obtained for each scale item had to be adequate, the largest item was 0.96 and the lowest was 0.69. The Kappa subscale was also evaluated and values were 0.84 for high frequency physic symptoms, 0.81 for low frequency physical symptoms, 0.81 for psychological symptoms, and 0.78 for Global Distress Index. High level of reliability estimated suggests that the process of measurement of Memorial Symptom Assessment Scale aspects was adequate. Avaliar a confiabilidade teste-reteste da versão traduzida e adaptada culturalmente para o português do Brasil do Memorial Symptom Assessment Scale. A escala foi aplicada em forma de entrevista em 190 pacientes com diversos tipos de câncer internados nos setores clínicos e cirúrgicos do Instituto Nacional de Câncer José de Alencar Gomes da Silva e reaplicada em 58 pacientes. Os dados dos testes-retestes foram inseridos num banco de dados por dupla digitação independente em Excel e analisados pelo Kappa ponderado. A confiabilidade da escala mostrou-se satisfatória nos testes-retestes. Os valores do Kappa ponderado obtidos para cada item da escala apresentaram-se adequados, sendo o maior item de 0,96 e o menor de 0,69. Também se avaliou o Kappa das subescalas, sendo de 0,84 para sintomas físicos de alta frequência, de 0,81 para sintomas físicos de baixa frequência, de 0,81 também para sintomas psicológicos, e de 0,78 para Índice Geral de Sofrimento

  20. Delirium superimposed on dementia versus delirium in the absence of dementia: phenomenological differences.

    PubMed

    Boettger, Soenke; Passik, Steven; Breitbart, William

    2009-12-01

    To examine differences in the phenomenological characteristics of delirium superimposed on dementia compared to those observed in delirious patients without dementia, based on the rating items of the Memorial Delirium Assessment Scale (MDAS). We conducted an analysis of a prospectively collected clinical delirium database utilized to record and monitor the care of delirious patients treated at Memorial Sloan-Kettering Cancer Center (MSKCC). Sociodemographic, medical variables, and MDAS total score and individual item ratings were analyzed in respect to differences between delirium in the demented (DD) versus delirium in the nondemented (ND). We were able to examine data collected on 100 delirious patients: 82 ND patients and 18 DD patients. Patients in the DD group, compared to the ND group, had significantly greater levels of disturbance of consciousness and impairments in all cognitive domains (i.e., orientation, short term memory, concentration, organization of thought process). Severe symptoms were more common in the DD group compared to the ND group on all the MDAS cognitive items as well as in disturbance of consciousness. There were no significant differences between the DD and ND groups in terms of presence or severity of hallucinations, delusions, psychomotor behavior, and sleep-wake cycle disturbance. Delirium superimposed on dementia has phenomenological differences compared to delirium in the absence of dementia. There are no significant differences in the severity of hallucinations, delusions, psychomotor behavior, or sleep-wake cycle disturbances. However, level of disturbance in consciousness (arousal and awareness) and impairments in multiple cognitive domains are significantly more severe in patients with delirium superimposed on dementia.

  1. A Clinical Framework to Facilitate Risk Stratification When Considering an Active Surveillance Alternative to Immediate Biopsy and Surgery in Papillary Microcarcinoma

    PubMed Central

    Brito, Juan P.; Ito, Yasuhiro; Miyauchi, Akira

    2016-01-01

    Background: The 2015 American Thyroid Association thyroid cancer management guidelines endorse an active surveillance management approach as an alternative to immediate biopsy and surgery in subcentimeter thyroid nodules with highly suspicious ultrasonographic characteristics and in cytologically confirmed very low risk papillary thyroid cancer (PTC). However, the guidelines provide no specific recommendations with regard to the optimal selection of patients for an active surveillance management approach. This article describes a risk-stratified clinical decision-making framework that was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma (PMC) who were being evaluated for an active surveillance management approach in the United States. Summary: A risk-stratified approach to the evaluation of patients with probable or proven PMC being considered for an active surveillance management approach requires an evaluation of three interrelated but distinct domains: (i) tumor/neck ultrasound characteristics (e.g., size of the primary tumor, the location of the tumor within the thyroid gland); (ii) patient characteristics (e.g., age, comorbidities, willingness to accept observation); and (iii) medical team characteristics (e.g., availability and experience of the multidisciplinary team). Based on an analysis of the critical factors within each of these domains, patients with probable or proven PTC can then be classified as ideal, appropriate, or inappropriate candidates for active surveillance. Conclusion: Risk stratification utilizing the proposed decision-making framework will improve the ability of clinicians to recognize individual patients with proven or probable PMC who are most likely to benefit from an active surveillance management option while at the same time identifying patients

  2. Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone.

    PubMed

    Konstantinidis, Ioannis T; Groot Koerkamp, Bas; Do, Richard K G; Gönen, Mithat; Fong, Yuman; Allen, Peter J; D'Angelica, Michael I; Kingham, T Peter; DeMatteo, Ronald P; Klimstra, David S; Kemeny, Nancy E; Jarnagin, William R

    2016-03-01

    Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone. Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing. Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months). In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society. © 2015 American Cancer Society.

  3. Robert R. Shaw, MD: thoracic surgical hero, Afghanistan medical pioneer, champion for the patient, never a surgical society president.

    PubMed

    Urschel, Harold C; Urschel, Betsey Bradley

    2012-06-01

    Dr Robert R. Shaw arrived in Dallas to practice Thoracic Surgery in 1937, as John Alexander's 7th Thoracic Surgical Resident from Michigan University Medical Center. Dr Shaw's modus operandi was, "You can accomplish almost anything, if you don't care who gets the credit." He was a remarkable individual who cared the most about the patient and very little about getting credit for himself. From 1937 to 1970, Dr Shaw established one of the largest lung cancer surgical centers in the world in Dallas, Texas. It was larger than M.D. Anderson and Memorial Sloan-Kettering Hospitals put together regarding the surgical treatment of lung cancer patients. To accomplish this, he had the help of Dr Donald L. Paulson, who trained at the Mayo Clinic and served as Chief of Thoracic Surgery at Brook Army Hospital during the Second World War. Following the War, because of his love for Texas, he ended up as a partner of Dr Shaw in Dallas. Together, they pursued the development of this very large surgical lung cancer center. Dr Shaw and his wife Ruth went to Afghanistan with Medico multiple times to teach men modern cardiac and thoracic surgery. They also served as consultants on Medico's Ship of Hope in Africa. Dr Shaw initiated multiple new operations including: 1) resection of Pancoast's cancer of the lung after preoperative irradiation; 2) upper lobe of the lung bronchoplasty, reattaching (and saving) the lower lobe to prevent the "disabling" pneumonectomy; and 3) resections of pulmonary mucoid impaction of the lung in asthmatics. Because of his humility and giving "the credit to others," Dr Shaw was never President of a major medical or surgical association.

  4. Normal development, oncogenesis and programmed cell death.

    PubMed

    Liebermann, D A

    1998-09-10

    Meeting's Report -- June 2, 1998, Sugarload Estate Conference Center, Philadelphia, Pennsylvania, USA. A symposium on Normal Development, Oncogenesis and Programmed Cell Death, was held at the Sugarload Estate Conference Center, Philadelphia, Pennsylvania, USA sponsored by the Fels Cancer Institute, Temple University School of Medicine, with the support of the Alliance Pharmaceutical Corporation. The symposium was organized by Drs Dan A Liebermann and Barbara Hoffman at the Fels. Invited speakers included: Dr Andrei V Gudkov (University of Illinois) who started the symposium talking about 'New cellular factors modulating the tumor suppressor function of p53'; Dr Yuri Lazebnik (Cold Spring Harbor Laboratories) spoke about 'Caspases considered as enemies within'; Dr E Premkumar Reddy (Fels Institute, Temple University) talked about recent exciting findings in his laboratory regarding 'JAK-STATs dedicated signaling pathways'; Dr Michael Greenberg (Harvard University) spoke about 'Signal transduction pathways that regulate differentiation and survival in the developing nervous system'; Dr Richard Kolesnick's (Memorial Sloan-Kettering Cancer Center) talk has been focused at 'Stress signals for apoptosis, including Ceramide and c-Jun Kinase/Stress-activated Protein Kinase'; Dr Barbara Hoffman (Fels Institute, Temple University) described research, conducted in collaboration with Dr Dan A Liebermann, aimed at deciphering the roles of 'myc, myb, and E2F as negative regulators of terminal differentiation', using hematopoietic cells as model system. Dr Daniel G Tenen (Harvard Medical School), described studies aimed at understanding the 'Regulation of hematopoietic cell development by lineage specific transcription regulators'. Dr George C Prendergast (The Wistar Institute) talked about the 'Myc-Bin1 signaling pathway in cell death and differentiation. Dr Ruth J Muschel (University of Pennsylvania) spoke about work, conducted in collaboration with Dr WG McKenna, aimed at

  5. The role of systemic chemotherapy in the management of granulosa cell tumors.

    PubMed

    Meisel, Jane L; Hyman, David M; Jotwani, Anjali; Zhou, Qin; Abu-Rustum, Nadeem R; Iasonos, Alexia; Pike, Malcolm C; Aghajanian, Carol

    2015-03-01

    Granulosa cell tumors (GCTs) are rare, and the role of chemotherapy in their management is not clearly defined. We performed a retrospective cohort study of GCT patients diagnosed from January 1996 through June 2013 at the Memorial Sloan Kettering Cancer Center, comparing those who received adjuvant chemotherapy to those who did not. Differences between groups were assessed using the log-rank test. Statistical significance was set at p<0.05. Of 118 patients, 10 (8%) received adjuvant chemotherapy (1 [1%] of 103 stage I and 9 [60%] of 15 stage II-IV patients). Thirty-two patients (27%) experienced disease recurrence. Four patients had residual disease after initial surgery, and all received adjuvant chemotherapy; each recurred within 24.3 months (median PFS, 8.2 months). The time to first recurrence was longer in patients who did not receive adjuvant chemotherapy. For patients with recurrent disease, receiving chemotherapy after surgery for first recurrence did not seem to improve time to second recurrence versus surgery alone (HR 0.98; p=0.965). Additionally, 12 patients (10%) had a previous diagnosis of breast cancer-an incidence rate 3.22 times higher than Surveillance, Epidemiology, and End Results (SEER) data predicts (p<0.001). Although the numbers were small, in this analysis chemotherapy was not found to improve the recurrence-free interval of patients with GCTs, a finding that requires prospective validation. Residual disease after surgery was associated with poor prognosis. Finally, there was a significantly higher than expected incidence of antecedent breast cancer in this population, an association that deserves further exploration. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Radiation-induced Breast Telangiectasias Treated with the Pulsed Dye Laser

    PubMed Central

    Rossi, Anthony M.; Nehal, Kishwer S.

    2014-01-01

    Background and objectives: Radiation dermatitis is a frequent sequela of adjuvant radiation therapy for breast cancer. Clinical manifestations include prominent telangiectasias that may be physically disfiguring and psychologically distressing for the patient. The objective of this study was to review cases of breast cancer patients with radiation-induced breast telangiectasias treated with the pulsed dye laser and assess clinical efficacy. The patient’s perception of treatment was also reviewed. Study design: A retrospective chart review of patients treated for radiation-induced telangiectasias was conducted at the Dermatology Division of Memorial Sloan-Kettering Cancer Center. Materials and methods: Pre- and post-clinical photos were used to assess clearance by two independent raters. Patient’s comments were assessed from visit notes and the treating physicians for the impact of treatment on the patient’s overall well-being. Results: All patients (n=11) experienced clinical improvement in the radiation-induced telangiectasias. The mean number of treatments was 4.3 (2–9) with an average fluence of 4.2J/cm2 (585nm platform) and 7.8J/cm2 (595nm) (4–8 J/cm2) used. The mean percent clearance was 72.7 percent (50–90%). Adverse effects were not encountered including those with breast implants or flap reconstruction. Patients reported an improvement in their well-being, including an improved sense of confidence. Limitations: Limitations include the small sample size, nonstandardized digital images, and nonsystematic collection of patient-reported outcomes. Conclusion: The pulsed dye laser is an efficacious treatment for radiation-induced breast telangiectasias. Multiple treatments are required for greater than 50-percent clearance and conservative treatment parameters are advised. Patients also reported an improved quality of life. PMID:25584136

  7. Radiation-induced Breast Telangiectasias Treated with the Pulsed Dye Laser.

    PubMed

    Rossi, Anthony M; Nehal, Kishwer S; Lee, Erica H

    2014-12-01

    Radiation dermatitis is a frequent sequela of adjuvant radiation therapy for breast cancer. Clinical manifestations include prominent telangiectasias that may be physically disfiguring and psychologically distressing for the patient. The objective of this study was to review cases of breast cancer patients with radiation-induced breast telangiectasias treated with the pulsed dye laser and assess clinical efficacy. The patient's perception of treatment was also reviewed. A retrospective chart review of patients treated for radiation-induced telangiectasias was conducted at the Dermatology Division of Memorial Sloan-Kettering Cancer Center. Pre- and post-clinical photos were used to assess clearance by two independent raters. Patient's comments were assessed from visit notes and the treating physicians for the impact of treatment on the patient's overall well-being. All patients (n=11) experienced clinical improvement in the radiation-induced telangiectasias. The mean number of treatments was 4.3 (2-9) with an average fluence of 4.2J/cm(2) (585nm platform) and 7.8J/cm(2) (595nm) (4-8 J/cm(2)) used. The mean percent clearance was 72.7 percent (50-90%). Adverse effects were not encountered including those with breast implants or flap reconstruction. Patients reported an improvement in their well-being, including an improved sense of confidence. LIMITATIONS include the small sample size, nonstandardized digital images, and nonsystematic collection of patient-reported outcomes. The pulsed dye laser is an efficacious treatment for radiation-induced breast telangiectasias. Multiple treatments are required for greater than 50-percent clearance and conservative treatment parameters are advised. Patients also reported an improved quality of life.

  8. Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma--An Infrequent Event: Elucidation of Risk Factors and Management Implications.

    PubMed

    Sahin, Ibrahim Halil; Geyer, Alexander I; Kelly, Daniel W; O'Reilly, Eileen Mary

    2016-03-01

    Gemcitabine-related pneumonitis (GRP) has been reported relatively frequently for pancreas cancer in the literature; however, underlying risk factors and optimal management remain to be defined. We studied a cohort of patients with GRP and investigated potential predisposing factors in pancreatic cancer patients. A total 2440 patients at Memorial Sloan Kettering Cancer Center were identified between January 1, 2000, and December 31, 2012, and were screened for grade 2 or higher GRP in an institutional tumor registry and using an ICD billing code database. Demographic and clinical information was extracted by electronic chart review. A total of 28 patients (1.1%) with GRP were identified. Incidence of grade 2, 3, and 4 reactions were 7 (25%), 18 (64%), and 3 (11%), respectively. No GRP-related mortality was observed. Twenty-one patients (75%) reported a history of cigarette smoking. Seventeen patients (61%) were alcohol users. Six patients (21%) were either regular or heavy drinkers. Most patients (93%) had either locally advanced or metastatic disease. Three patients (11%) underwent a diagnostic bronchoscopy, and in 1 patient a diagnosis of organizing pneumonia was established. Morbidity was significant; 3 patients (11%) required treatment in the intensive care unit. All hospitalized patients received steroid treatment. GRP is relatively uncommon but incurs significant morbidity. Potential risk factors include advanced-stage disease, along with smoking and alcohol consumption and possibly underlying lung disease. We recommend a high level of clinical alertness regarding the diagnosis, early pulmonary referral, and cessation of gemcitabine on suspicion of GRP. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes.

    PubMed

    Naidoo, Jarushka; Santos-Zabala, Maria L; Iyriboz, Tunc; Woo, Kaitlin M; Sima, Camelia S; Fiore, John J; Kris, Mark G; Riely, Gregory J; Lito, Piro; Iqbal, Afsheen; Veach, Stephen; Smith-Marrone, Stephanie; Sarkaria, Inderpal S; Krug, Lee M; Rudin, Charles M; Travis, William D; Rekhtman, Natasha; Pietanza, Maria C

    2016-09-01

    Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort. Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Myxoid fibroadenomas differ from conventional fibroadenomas: a hypothesis-generating study.

    PubMed

    Lozada, John R; Burke, Kathleen A; Maguire, Aoife; Pareja, Fresia; Lim, Raymond S; Kim, Jisun; Gularte-Merida, Rodrigo; Murray, Melissa P; Brogi, Edi; Weigelt, Britta; Reis-Filho, Jorge S; Geyer, Felipe C

    2017-10-01

    Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs. Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture-microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon histological re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR1A somatic mutation was restricted to the stromal component. MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers. © 2017 John Wiley & Sons Ltd.

  11. Efficacy and safety of sorafenib versus sunitinib as first-line treatment in patients with metastatic renal cell carcinoma: largest single-center retrospective analysis

    PubMed Central

    Cui, Chuanliang; Si, Lu; Li, Siming; Tang, Bixia; Mao, Lili; Lian, Bin; Wang, Xuan; Yan, Xieqiao; Guo, Jun

    2016-01-01

    We conducted this largest, single-center, retrospective study to determine the efficacy of sorafenib versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) in Chinese patients to validate the potential data on direct comparison of the efficacy of first-line treatment with sorafenib and sunitinib in the treatment of mRCC. From November 2006 to March 2015, we reviewed medical records from Peking University Cancer Hospital and found 169 patients receiving sorafenib (400 mg orally BID continuously in a 4-week cycle) and 165 patients receiving sunitinib (50 mg orally daily in a 6-week cycle; 4/2 schedule) as the first-line targeted therapy. Median follow-up was 23.0 months. In sorafenib and sunitinib groups, there is no significant difference in progression-free survival (PFS) (9.0 months [95%CI:8.00-12.00] vs 11.0 months [95%CI:9.00-14.00], respectively; P=0.6289) and overall survival (OS) (28.0 months [95%CI:24.00-34.00] vs 28.0 months [95% CI:19.00-33.00], respectively; P=0.979). Subgroup analysis based on Karnofsky performance status (KPS), pathological type, Memorial Sloan Kettering Cancer Center score, and metastasis was also conducted. Multivariate analysis revealed that sorafenib treated patients had superior efficacy in patients with a KPS of <90 and significantly better PFS (hazard ratio: 0.460 [95% CI:0.222-0.954]). Most common adverse events were hand-foot skin reaction and thrombocytopenia which were manageable. Overall, no significant differences were seen between sorafenib and sunitinib in the treatment of advanced renal cancer. However, fewer toxicities associated with sorafenib and superior efficacy in subgroups (non-clear cell carcinoma and KPS <90) indicates sorafenib as an effective first-line treatment agent in patients with mRCC. PMID:26894858

  12. Aripiprazole and haloperidol in the treatment of delirium.

    PubMed

    Boettger, Soenke; Friedlander, Miriam; Breitbart, William; Passik, Steven

    2011-06-01

    To compare the efficacy and tolerability of aripiprazole and haloperidol in the amelioration of distressing symptoms of delirium and its motoric subtypes. At Memorial Sloan-Kettering Cancer Center, we prospectively collected sociodemographic and medical data and systematically rated all patients diagnosed with delirium with the Memorial Delirium Assessment Scale (MDAS), Karnofsky Performance Scale (KPS) and the abbreviated Udvalg Kliniske Undersogelser Side Effect Rating Scale (UKU) at the initial diagnosis of delirium (T1), after 48-72 h (T2) and 7 days later (T3). All collected information was entered into a delirium database. For our analysis, we subsequently extracted data on aripiprazole (ARI) treated patients to compare to case-matched haloperidol (HAL) treated patients. We retrieved 21 patients treated with aripiprazole and 21 case-matched patients treated with haloperidol. Initial MDAS scores did not significantly differ between the groups. Over the course of treatment (T1 to T3), MDAS scores improved from 18.1 to 8.3 for ARI and 19.9 to 6.8 for HAL. The delirium resolution rate was 76.2% for ARI and 76.2% for HAL. For patients with hypoactive delirium, the MDAS scores improved from 15.6 to 5.7 for ARI and 18.8 to 8.1 for HAL. Delirium resolution rates for patients with hypoactive delirium were 100% for ARI and 77.8% for HAL. For patients experiencing hyperactive delirium, the MDAS scores improved from 19.9 to 6.8 for ARI and 20.8 to 5.8 for HAL. Delirium resolution rates for patients with hyperactive delirium were 58.3% for ARI and 75% for HAL. There were no significant differences in treatment results between ARI and HAL. Treatment with HAL caused more extrapyramidal side effects. From our secondary analysis, aripiprazole may be as effective as haloperidol in the management of delirium and its subtypes. Treatment with haloperidol resulted in more side effects.

  13. Delineation of antigen-specific and antigen-nonspecific CD8+ memory T-cell responses after cytokine-based cancer immunotherapy

    PubMed Central

    Tietze, Julia K.; Wilkins, Danice E. C.; Sckisel, Gail D.; Bouchlaka, Myriam N.; Alderson, Kory L.; Weiss, Jonathan M.; Ames, Erik; Bruhn, Kevin W.; Craft, Noah; Wiltrout, Robert H.; Longo, Dan L.; Lanier, Lewis L.; Blazar, Bruce R.; Redelman, Doug

    2012-01-01

    Memory T cells exhibit tremendous antigen specificity within the immune system and accumulate with age. Our studies reveal an antigen-independent expansion of memory, but not naive, CD8+ T cells after several immunotherapeutic regimens for cancer resulting in a distinctive phenotype. Signaling through T-cell receptors (TCRs) or CD3 in both mouse and human memory CD8+ T cells markedly up-regulated programmed death-1 (PD-1) and CD25 (IL-2 receptor α chain), and led to antigen-specific tumor cell killing. In contrast, exposure to cytokine alone in vitro or with immunotherapy in vivo did not up-regulate these markers but resulted in expanded memory CD8+ T cells expressing NKG2D, granzyme B, and possessing broadly lytic capabilities. Blockade of NKG2D in mice also resulted in significantly diminished antitumor effects after immunotherapy. Treatment of TCR-transgenic mice bearing nonantigen expressing tumors with immunotherapy still resulted in significant antitumor effects. Human melanoma tissue biopsies obtained from patients after topically applied immunodulatory treatment resulted in increased numbers of these CD8+ CD25− cells within the tumor site. These findings demonstrate that memory CD8+ T cells can express differential phenotypes indicative of adaptive or innate effectors based on the nature of the stimuli in a process conserved across species. PMID:22251483

  14. Ovarian cancer: contribution of radiation therapy to patient management: Erskine Memorial Lecture, 1983

    SciTech Connect

    Bush, R.S.

    1984-10-01

    Ovarian cancer may be treated with radiation therapy, surgery, chemotherapy, or a combination. To evaluate the contribution of radiation therapy to patient management the cure rate must be estimated; data are presented suggesting that the 5-year survival rate provides a reasonable estimate of the cure rate. A study of patients treated since 1971 showed that stage and postoperative residuum could be used to divide patients into two subgroups, a poor prognosis group and a good prognosis group; a multifactorial grouping of patients in the good prognosis group who were treated postoperatively with radiation therapy only was further able to divide patients into low-risk, intermediate-risk, and high-risk groups. Studies of radiation therapy for different subgroups are discussed; abdominopelvic irradiation has been shown to improve survival for approximately one-third of patients with cancer of the ovary.

  15. Extending the validity of the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) at the time of prostate biopsy in a racially-mixed population.

    PubMed

    Dale, William; Hemmerich, Joshua; Meltzer, David

    2007-05-01

    The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) has been validated for assessing men with prostate cancer for cancer-specific anxiety. It was originally validated in a predominantly white population. The MAX-PC Prostate Cancer Anxiety Subscale (MAX-PC-PCAS) may be relevant for measuring cancer-specific anxiety in undiagnosed men at risk for prostate cancer. We assess the validity of the MAX-PC-PCAS at the time of prostate biopsy (n = 178). Questions assessed socio-demographic information, health status, patient-estimated risk of cancer, the Hospital Anxiety and Depression Scale--Anxiety Subscale (HADS-A), and the MAX-PC-PCAS. The patients' most recent PSA was recorded. Cronbach's alpha, inter-item correlations, and Pearson correlations with both the HADS-A and clinical variables were compared with the original validation sample. Our sample was younger (63.1 vs 71.1 years), had a larger fraction of African-Americans (43 vs 10%), and had higher PSAs. Cronbach's alpha was equivalent (0.91 vs 0.90), median inter-item correlation was equivalent (0.63 vs 0.61), and Pearson correlation with HADS-A was higher (0.71 vs 0.57). Anxiety levels were not correlated with PSA levels, and there were minor differences in the validation findings by race. The validity of the MAX-PC-PCAS extends to men without cancer undergoing biopsy and to African-Americans.

  16. Bivalent domains enforce transcriptional memory of DNA methylated genes in cancer cells.

    PubMed

    Rodriguez, Jairo; Muñoz, Mar; Vives, Laura; Frangou, Costas G; Groudine, Mark; Peinado, Miguel A

    2008-12-16

    Silencing of multiple cancer-related genes is associated with de novo methylation of linked CpG islands. Additionally, bivalent histone modification profiles characterized by the juxtaposition of active and inactive histone marks have been observed in genes that become hypermethylated in cancer. It is unknown how these ambiguous epigenetic states are maintained and how they interrelate with adjacent genomic regions with different epigenetic landscapes. Here, we present the analysis of a set of neighboring genes, including many frequently silenced in colon cancer cells, in a chromosomal region at 5q35.2 spanning 1.25 Mb. Promoter DNA methylation occurs only at genes maintained at a low transcriptional state and is characterized by the presence of bivalent histone marks, namely trimethylation of lysines 4 and 27 in histone 3. Chemically induced hyperacetylation and DNA demethylation lead to up-regulation of silenced genes in this locus yet do not resolve bivalent domains into a domain-wide active chromatin conformation. In contrast, active genes in the region become down-regulated after drug treatment, accompanied by a partial loss of chromatin domain boundaries and spreading of the inactive histone mark trimethylated lysine 27 in histone 3. Our results demonstrate that bivalent domains mark the promoters of genes that will become DNA methylated in adult tumor cells to enforce transcriptional silence. These bivalent domains not only remain upon drug induced gene reactivation, but also spread over adjacent CpG islands. These results may have important implications in understanding and managing epigenetic therapies of cancer.

  17. Missing memories of death: Dissociative amnesia in the bereaved the day after a cancer death.

    PubMed

    Ishida, Mayumi; Onishi, Hideki; Toyama, Hiroaki; Tsutsumi, Chizuko; Endo, Chieko; Tanahashi, Iori; Takahashi, Takao; Uchitomi, Yosuke

    2015-12-01

    The death of a loved one is one of the most stressful events of life, and such stress affects the physical and psychological well-being of the bereaved. Dissociative amnesia is characterized by an inability to recall important autobiographical information. Dissociative amnesia in the bereaved who have lost a loved one to cancer has not been previously reported. We discuss herein the case of a patient who developed dissociative amnesia the day after the death of here beloved husband. A 38-year-old woman was referred for psychiatric consultation because of restlessness and abnormal behavior. Her 44-year-old husband had died of pancreatic cancer the day before the consultation. On the day of the death, she looked upset and began to hyperventilate. The next day, she behaved as if the deceased were still alive, which embarrassed her family. At her initial psychiatric consultation, she talked and behaved as if her husband was still alive and in the hospital. Her psychiatric features fulfilled the DSM-V criteria for dissociative amnesia. The death of her husband had been very traumatic for her and was considered to have been one of the causes of this dissociation. This report adds to the list of psychiatric symptoms in the bereaved who have lost a loved one to cancer. In an oncology setting, we should consider the impact of death, the concomitant defense mechanisms, and the background of the families.

  18. Chemical & RNAi screening at MSKCC: a collaborative platform to discover & repurpose drugs to fight disease.

    PubMed

    Bhinder, Bhavneet; Antczak, Christophe; Shum, David; Radu, Constantin; Mahida, Jeni P; Liu-Sullivan, Nancy; Ibanez, Glorymar; Raja, Balajee Somalinga; Calder, Paul A; Djaballah, Hakim

    2014-05-01

    Memorial Sloan Kettering Cancer Center (MSKCC) has implemented the creation of a full service state-of-the-art High-throughput Screening Core Facility (HTSCF) equipped with modern robotics and custom-built screening data management resources to rapidly store and query chemical and RNAi screening data outputs. The mission of the facility is to provide oncology clinicians and researchers alike with access to cost-effective HTS solutions for both chemical and RNAi screening, with an ultimate goal of novel target identification and drug discovery. HTSCF was established in 2003 to support the institution's commitment to growth in molecular pharmacology and in the realm of therapeutic agents to fight chronic diseases such as cancer. This endeavor required broad range of expertise in technology development to establish robust and innovative assays, large collections of diverse chemical and RNAi duplexes to probe specific cellular events, sophisticated compound and data handling capabilities, and a profound knowledge in assay development, hit validation, and characterization. Our goal has been to strive for constant innovation, and we strongly believe in shifting the paradigm from traditional drug discovery towards translational research now, making allowance for unmet clinical needs in patients. Our efforts towards repurposing FDA-approved drugs fructified when digoxin, identified through primary HTS, was administered in the clinic for treatment of stage Vb retinoblastoma. In summary, the overall aim of our facility is to identify novel chemical probes, to study cellular processes relevant to investigator's research interest in chemical biology and functional genomics, and to be instrumental in accelerating the process of drug discovery in academia.

  19. Next-Generation Assessment of Human Epidermal Growth Factor Receptor 2 (ERBB2) Amplification Status: Clinical Validation in the Context of a Hybrid Capture-Based, Comprehensive Solid Tumor Genomic Profiling Assay.

    PubMed

    Ross, Dara S; Zehir, Ahmet; Cheng, Donavan T; Benayed, Ryma; Nafa, Khedoudja; Hechtman, Jaclyn F; Janjigian, Yelena Y; Weigelt, Britta; Razavi, Pedram; Hyman, David M; Baselga, José; Berger, Michael F; Ladanyi, Marc; Arcila, Maria E

    2017-03-01

    Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to treatment selection. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. Next-generation sequencing (NGS) is an attractive approach for up-front comprehensive assessment, including ERBB2 status, but the concordance with traditional methods of HER2 assessment is not well established. The Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, a hybrid capture-based NGS assay interrogating the coding regions of 410 cancer-related genes, was performed on manually macrodissected unstained sections from formalin-fixed, paraffin-embedded breast (n = 213) and gastroesophageal (n = 39) tumors submitted for clinical mutation profiling. ERBB2 status was assessed using a custom bioinformatics pipeline, and NGS results were compared to IHC and FISH. NGS ERBB2 amplification calls had an overall concordance of 98.4% (248/252) with the combined IHC/FISH results in this validation set. Discrepancies occurred in the context of low tumor content and HER2 heterogeneity. ERBB2 amplification status can be reliably determined by hybridization capture-based NGS methods, allowing efficient concurrent testing for other potentially actionable genomic alterations, particularly in limited material. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  20. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

    PubMed Central

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Tuttle, R Michael; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-01-01

    ETV6–NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47–72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6–NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated

  1. New roles & responsibilities of hospital biomedical engineering.

    PubMed

    Frisch, P H; Stone, B; Booth, P; Lui, W

    2014-01-01

    Over the last decade the changing healthcare environment has required hospitals and specifically Biomedical Engineering to critically evaluate, optimize and adapt their operations. The focus is now on new technologies, changes to the environment of care, support requirements and financial constraints. Memorial Sloan Kettering Cancer Center (MSKCC), an NIH-designated comprehensive cancer center, has been transitioning to an increasing outpatient care environment. This transition is driving an increase in-patient acuity coupled with the need for added urgency of support and response time. New technologies, regulatory requirements and financial constraints have impacted operating budgets and in some cases, resulted in a reduction in staffing. Specific initiatives, such as the Joint Commission's National Patient Safety Goals, requirements for an electronic medical record, meaningful use and ICD10 have caused institutions to reevaluate their operations and processes including requiring Biomedical Engineering to manage new technologies, integrations and changes in the electromagnetic environment, while optimizing operational workflow and resource utilization. This paper addresses the new and expanding responsibilities and approach of Biomedical Engineering organizations, specifically at MSKCC. It is suggested that our experience may be a template for other organizations facing similar problems. Increasing support is necessary for Medical Software - Medical Device Data Systems in the evolving wireless environment, including RTLS and RFID. It will be necessary to evaluate the potential impact on the growing electromagnetic environment, on connectivity resulting in the need for dynamic and interactive testing and the growing demand to establish new and needed operational synergies with Information Technology operations and other operational groups within the institution, such as nursing, facilities management, central supply, and the user departments.

  2. ORNL production of the experimental alpha emitters bismuth-213 and actinium-225 for medical applications

    SciTech Connect

    Webb, O.F.; Krichinsky, A.M.; Yong, L.K.

    1998-09-01

    Due to their short range in tissue (50 to 80 {micro}m), alpha emitters are of considerable interest for certain radioimmunotherapy applications. These applications require the destruction of single cells or small clusters of cells. The radioisotope {sup 213}Bi, which is milked from {sup 225}Ac, is an alpha emitter that is currently being used in phase-1 human leukemia trials at the Memorial Sloan-Kettering Cancer Center. The most readily achievable route for producing {sup 225}Ac generators involves separating ingrown {sup 229}Th daughters from the {sup 233}U parent. Thorium-229 is then used as a parent generator for {sup 225}Ac. Thorium-229 is easier to handle than {sup 233}U, which is fissile and typically contains trace concentrations of {sup 232}U. Uranium-232 has a radioactive daughter, {sup 208}Tl, which emits a high-energy (2.6-MeV) photon when it decays. An alternative method for producing {sup 229}Th is through neutron irradiation of {sup 227}Ra. However, this method is less desirable due to the production of very high levels of {sup 228}Th. Thorium-229 accumulates in stored {sup 233}U oxides by natural decay. The current ORNL process for extracting {sup 229}Th from stored {sup 233}U oxides includes dissolution, strong-acid anion exchange, and calcination of the uranium. This ORNL process has provided high-purity {sup 225}Ac generators to medical researchers. Bismuth-213 has been extracted and used in initial human trials and already has demonstrated a potency and specificity for attacking cancerous cells.

  3. Comparison of Outcomes at Two Institutions of Patients with Acute Lymphoblastic Leukemia Receiving Ex-Vivo T-Cell Depleted or Unmodified Allografts

    PubMed Central

    Hobbs, Gabriela S.; Hamdi, Amir; Hilden, Patrick D.; Goldberg, Jenna D.; Poon, Michelle L.; Ledesma, Celina; Devlin, Sean M.; Rondon, Gabriela; Papadopoulos, Esperanza B.; Jakubowski, Ann A.; O'Reilly, Richard J.; Champlin, Richard E.; Giralt, Sergio; Perales, Miguel-Angel; Kebriaei, Partow

    2015-01-01

    We compared outcomes of adult patients receiving T-cell depleted (TCD) hematopoietic stem cell transplantation (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52) with patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for acute lymphoblastic leukemia in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received ATG at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (p=0.001, 17.3% vs. 42.6% at 100 days) and chronic GVHD (p=0.006, 13.5% vs. 33.4% at 3 years) were significantly lower in the TCD group. The NRM at day 100, 1 and 3 years was 15.4%, 25.0% and 35.9% in the TCD group and 9.6%, 23.6% and 28.6% in the unmodified group (p=0.368). There was no difference in relapse (p=0.107, 21.3% vs. 35.5% at 3 years), OS (p=0.854, 42.6% vs. 43.0% at 3 years), or RFS (p=0.653, 42.8% vs. 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (HR=2.16, p=0.003, HR=1.77, p =0.022, HR=2.47, p<0.001), while graft type was not significant (HR=0.90, p=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD. PMID:25621808

  4. Chemical & RNAi screening at MSKCC: a collaborative platform to discover & repurpose drugs to fight disease

    PubMed Central

    Bhinder, Bhavneet; Antczak, Christophe; Shum, David; Radu, Constantin; Mahida, Jeni P.; Liu-Sullivan, Nancy; Ibáñez, Glorymar; Raja, Balajee Somalinga; Calder, Paul A.; Djaballah, Hakim

    2014-01-01

    Memorial Sloan-Kettering Cancer Center (MSKCC) has implemented the creation of a full service state-of-the-art High-throughput Screening Core Facility (HTSCF) equipped with modern robotics and custom-built screening data management resources to rapidly store and query chemical and RNAi screening data outputs. The mission of the facility is to provide oncology clinicians and researchers alike with access to cost-effective HTS solutions for both chemical and RNAi screening, with an ultimate goal of novel target identification and drug discovery. HTSCF was established in 2003 to support the institution’s commitment to growth in molecular pharmacology and in the realm of therapeutic agents to fight chronic diseases such as cancer. This endeavor required broad range of expertise in technology development to establish robust and innovative assays, large collections of diverse chemical and RNAi duplexes to probe specific cellular events, sophisticated compound and data handling capabilities, and a profound knowledge in assay development, hit validation, and characterization. Our goal has been to strive for constant innovation, and we strongly believe in shifting the paradigm from traditional drug discovery towards translational research now, making allowance for unmet clinical needs in patients. Our efforts towards repurposing FDA-approved drugs fructified when digoxin, identified through primary HTS, was administered in the clinic for treatment of stage Vb retinoblastoma. In summary, the overall aim of our facility is to identify novel chemical probes, to study cellular processes relevant to investigator’s research interest in chemical biology and functional genomics, and to be instrumental in accelerating the process of drug discovery in academia. PMID:24661215

  5. Why Value Framework Assessments Arrive at Different Conclusions: A Multiple Myeloma Case Study.

    PubMed

    Westrich, Kimberly; Buelt, Lisabeth; Dubois, Robert W

    2017-06-01

    As the United States transitions from a volume-based health care system to one that rewards value, new frameworks are emerging to help patients, providers, and payers assess the value of medical services and biopharmaceutical products. These value assessment frameworks are intended to support various types of health care decision making. They have the potential to substantially affect patients, whether as tools for shared decision making with their doctors, as an input to care pathways used by providers, or through payer use of the frameworks to make coverage or reimbursement decisions. Prominent among current U.S. value assessment frameworks are those developed by the American Society of Clinical Oncology, the Institute for Clinical and Economic Review, the Memorial Sloan Kettering Cancer Center, and the National Comprehensive Cancer Network. These frameworks generally reflect the interests and expertise of the organizations that developed them. The evidence, methodology, and intended use differ substantially across frameworks, which can lead to highly variable determinations of value for the same treatment therapy. To demonstrate this variability, we explored how these frameworks assess the value of treatment regimens for multiple myeloma. Cross-framework comparisons of multiple myeloma assessments were conducted, and consistency of findings was examined for 3 case studies. A discussion of the analysis explores why different frameworks arrive at different conclusions, whether those differences are cause for concern, and the resulting implications for framework readiness to support health care decision making. Funding for this project was provided by the National Pharmaceutical Council. The authors are employees of the National Pharmaceutical Council, an industry-funded health policy research group that is not involved in lobbying or advocacy. Study concept and design were contributed by Westrich and Dubois, along with Buelt. Westrich took the lead in data

  6. Development of a risk stratification system to guide treatment for female germ cell tumors.

    PubMed

    Meisel, Jane L; Woo, Kaitlin M; Sudarsan, Nora; Eng, Jana; Patil, Sujata; Jacobsen, Erin P; Murali, Rajmohan; Gardner, Ginger J; Bosl, George J; Aghajanian, Carol; Feldman, Darren R

    2015-09-01

    Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer. Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome. Of 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76-92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12). Modified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older.

    PubMed

    Feldman, Darren R; Voss, Martin H; Jacobsen, Erin P; Jia, Xiaoyu; Suarez, J Andres; Turkula, Stefan; Sheinfeld, Joel; Bosl, George J; Motzer, Robert J; Patil, Sujata

    2013-07-15

    Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking. Patients with GCT seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were identified. Primary tumor site and histology were compared for patients aged ≥  50 years at diagnosis versus younger men. For patients aged ≥  50, individual chart review was performed and treatment delays, changes, and toxicities were recorded for those treated with first-line chemotherapy. Of 4235 diagnoses of GCT, 3999 (94.4%) were made at age  <  50 versus 236 (5.6%) at age  ≥  50. Compared with patients diagnosed before age 50, older men more frequently had seminoma (62.7% versus 36.7%) and less frequently, nonseminoma (34.7% versus 63.2%) (P  < .0001). Predominant histology switched from nonseminoma to seminoma around age 35. Distribution of primary sites also differed for older versus younger men (testis: 89.4% versus 92.9%; retroperitoneal: 3.8% versus 0.7%; CNS 0% versus 1.7%) except for mediastinal primary tumors, which remained constant across age groups. Fifty patients age  ≥  50 received first-line platinum-based chemotherapy; 30 experienced complications leading to treatment discontinuation, delay  ≥  7 days, or regimen change. Twenty-two (44%) patients experienced neutropenic fever, 6 despite prophylactic growth factor support. Estimated 5-year survival for chemotherapy-treated patients was 84.9%. Men aged ≥ 50 years comprise less than 10% of GCT diagnoses and have distinct clinical and histological characteristics as compared with younger patients. Although complications from chemotherapy occur frequently in older men, prognosis remains excellent when risk-directed treatment is administered with curative intent. © 2013 American Cancer Society.

  8. Mifamurtide in osteosarcoma--a practical review.

    PubMed

    Anderson, P M; Tomaras, M; McConnell, K

    2010-05-01

    Mifamurtide, also known as liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE), has been approved for the treatment of osteosarcoma in Europe. Mifamurtide's rational drug design employs MTP-PE for macrophage activation in a multilamellar liposome drug carrier, containing the synthetic phospholipids 1-palmitoyl-2-oleoyl phosphatidyl choline (POPC) and 1,2-dioleoyl phosphatidyl serine (OOPS). Although the drug is not cytotoxic towards normal or tumor cells in vitro, immune activation against osteosarcoma lung metastases in vivo accounts for mifamurtide's antiosteosarcoma effects. Phosphatidyl serine-containing lipids signal macrophage cells that have "flipped phosphatidyl serine" to the outer membrane after apoptosis (e.g., after damage of tumor cells from chemotherapy); thus, both mifamurtide's active and inactive ingredients target immune cells in the lungs. Mifamurtide administration has resulted in 8% and 13% improvement in 6- and 5-year overall survivals, when added to chemotherapy in nonmetastatic and metastatic patients with osteosarcoma, respectively. The short-term toxicities of mifamurtide (fever, headache, flu-like symptoms and rigors) are reduced or eliminated using ibuprofen (200 mg) as premedication for the first infusion; an algorithm for pre- and postmedication is presented. To date, no long-term side effects of mifamurtide have been reported. Compassionate access programs based in two major cancer centers (MD Anderson and Memorial Sloan-Kettering), have recently provided this potentially life-saving drug in North America. The experience with mifamurtide provides an outstanding example of successful cooperation among regulatory bodies and agencies, the pharmaceutical industry and pediatric oncologists to improve cancer care and outcomes for children and young people with a rare sarcoma. Copyright (c) 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  9. Clinical Application of Picodroplet Digital PCR Technology for Rapid Detection of EGFR T790M in Next-Generation Sequencing Libraries and DNA from Limited Tumor Samples.

    PubMed

    Borsu, Laetitia; Intrieri, Julie; Thampi, Linta; Yu, Helena; Riely, Gregory; Nafa, Khedoudja; Chandramohan, Raghu; Ladanyi, Marc; Arcila, Maria E

    2016-11-01

    Although next-generation sequencing (NGS) is a robust technology for comprehensive assessment of EGFR-mutant lung adenocarcinomas with acquired resistance to tyrosine kinase inhibitors, it may not provide sufficiently rapid and sensitive detection of the EGFR T790M mutation, the most clinically relevant resistance biomarker. Here, we describe a digital PCR (dPCR) assay for rapid T790M detection on aliquots of NGS libraries prepared for comprehensive profiling, fully maximizing broad genomic analysis on limited samples. Tumor DNAs from patients with EGFR-mutant lung adenocarcinomas and acquired resistance to epidermal growth factor receptor inhibitors were prepared for Memorial Sloan-Kettering-Integrated Mutation Profiling of Actionable Cancer Targets sequencing, a hybrid capture-based assay interrogating 410 cancer-related genes. Precapture library aliquots were used for rapid EGFR T790M testing by dPCR, and results were compared with NGS and locked nucleic acid-PCR Sanger sequencing (reference high sensitivity method). Seventy resistance samples showed 99% concordance with the reference high sensitivity method in accuracy studies. Input as low as 2.5 ng provided a sensitivity of 1% and improved further with increasing DNA input. dPCR on libraries required less DNA and showed better performance than direct genomic DNA. dPCR on NGS libraries is a robust and rapid approach to EGFR T790M testing, allowing most economical utilization of limited material for comprehensive assessment. The same assay can also be performed directly on any limited DNA source and cell-free DNA.

  10. Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma–like and Non–Small Cell Carcinoma–like Subsets

    PubMed Central

    Rekhtman, Natasha; Pietanza, Maria C.; Hellmann, Matthew D.; Naidoo, Jarushka; Arora, Arshi; Won, Helen; Halpenny, Darragh F.; Wang, Hangjun; Tian, Shaozhou K.; Litvak, Anya M.; Paik, Paul K.; Drilon, Alexander E.; Socci, Nicholas; Poirier, John T.; Shen, Ronglai; Berger, Michael F.; Moreira, Andre L.; Travis, William D.; Rudin, Charles M.; Ladanyi, Marc

    2016-01-01

    Purpose Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm, whose biologic relationship to small cell lung carcinoma (SCLC) versus non-SCLC (NSCLC) remains unclear, contributing to uncertainty regarding optimal clinical management. To clarify these relationships, we analyzed genomic alterations in LCNEC compared with other major lung carcinoma types. Experimental Design LCNEC (n = 45) tumor/normal pairs underwent targeted next-generation sequencing of 241 cancer genes by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) platform and comprehensive histologic, immunohistochemical, and clinical analysis. Genomic data were compared with MSK-IMPACT analysis of other lung carcinoma histologies (n = 242). Results Commonly altered genes in LCNEC included TP53 (78%), RB1 (38%), STK11 (33%), KEAP1 (31%), and KRAS (22%). Genomic profiles segregated LCNEC into 2 major and 1 minor subsets: SCLC-like (n = 18), characterized by TP53+RB1 co-mutation/loss and other SCLC-type alterations, including MYCL amplification; NSCLC-like (n = 25), characterized by the lack of coaltered TP53+RB1 and nearly universal occurrence of NSCLC-type mutations (STK11, KRAS, and KEAP1); and carcinoid-like (n = 2), characterized by MEN1 mutations and low mutation burden. SCLC-like and NSCLC-like subsets revealed several clinicopathologic differences, including higher proliferative activity in SCLC-like tumors (P < 0.0001) and exclusive adenocarcinoma-type differentiation marker expression in NSCLC-like tumors (P = 0.005). While exhibiting predominant similarity with lung adenocarcinoma, NSCLC-like LCNEC harbored several distinctive genomic alterations, including more frequent mutations in NOTCH family genes (28%), implicated as key regulators of neuroendocrine differentiation. Conclusions LCNEC is a biologically heterogeneous group of tumors, comprising distinct subsets with genomic signatures of SCLC, NSCLC (predominantly

  11. Educational and Psychosocial Support Needs in Lynch Syndrome: Implementation and Assessment of an Educational Workshop and Support Group.

    PubMed

    Corines, Marina J; Hamilton, Jada G; Glogowski, Emily; Anrig, Chris A; Goldberg, Rachael; Niehaus, Kate; Salo-Mullen, Erin; Harlan, Megan; Sheehan, Margaret R; Trottier, Magan; Ahsraf, Asad; Tran, Christina; Jacobs, Lauren; Rau-Murthy, Rohini; Lincoln, Anne G; Robson, Mark E; Guillem, Jose G; Markowitz, Arnold J; Offit, Kenneth; Stadler, Zsofia K

    2017-04-01

    Few reports of educational and counseling support resources exist for Lynch syndrome (LS), a disorder requiring multi-organ cancer screening and specialized medical care throughout adult life. Here we describe the development and efficacy of two resources designed to address this need, the Memorial Sloan Kettering Cancer Center Clinical Genetics Service annual Lynch Syndrome Educational Workshop (LSEW), and a quarterly Lynch Syndrome Patient Advocacy Network (LSPAN) support group. The LSEW and LSPAN were implemented beginning in 2012. Participant survey data evaluating satisfaction, clarity, and unmet needs for each event were retrospectively analyzed and summarized using descriptive statistics. Annual LSEW attendance ranged from 53 to 75 total participants. LSEW year 1 participants indicated a need for a support group, and preferred in-person meetings at a frequency of every 3-6 months. For LSEW year 2-5 participants, >96 % reported satisfaction with the LSEW, and >82 % expressed interest in secure online support. Common themes for improvement included increased time for question and answer sessions and additional introductory genetics education. Responding LSPAN participants (n = 57 total survey responses in 11 meetings) found the meetings helpful (100 %), information clear (91 %), and presence of a genetic counselor useful (67 %). Desired discussion topics included coping with stress and anxiety, development of a support network, family communication about LS, genetic testing decisions, and bereavement. Following genetic counseling, a need exists for ongoing educational and emotional support in LS. Implementation of resources such as the LSEW and LSPAN is feasible and perceived as helpful by participants.

  12. Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients.

    PubMed

    Conroy, Melissa J; Galvin, Karen C; Doyle, Suzanne L; Kavanagh, Maria E; Mongan, Ann-Marie; Cannon, Aoife; Moore, Gillian Y; Reynolds, John V; Lysaght, Joanne

    2016-10-01

    In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum and liver of patients with the obesity-associated malignancy oesophageal adenocarcinoma (OAC). Furthermore, we assessed the secreted cytokine profile in OAC patient serum, omentum and liver to assess systemic and local inflammation. We observed parallel T cell cytokine profiles and phenotypes in the omentum and liver of OAC patients, in particular CD69(+) and inflammatory effector memory T cells. This study reflects similar processes of inflammation and T cell activation in the omentum and liver, and may suggest common targets to modulate pathological inflammation at these sites.

  13. Stem-Like Memory T Cells Are Discovered | Center for Cancer Research

    Cancer.gov

    T cells are the white blood cells that are the body’s first line of attack against foreign invaders.  When designing immunotherapies to treat cancer the goal is to prolong the immune response of T cells a bit beyond what the body normally does when a bacterium or a virus is encountered.   Nicholas P. Restifo, M.D., working with Luca Gattinoni, M.D., and other colleagues in CCR’s Surgery Branch recently discovered a subset within the human T cell population that may help clinicians to do just  this.

  14. Nutritional status in survivors of childhood cancer: Experience from Tata Memorial Hospital, Mumbai.

    PubMed

    Prasad, M; Arora, B; Chinnaswamy, G; Vora, T; Narula, G; Banavali, S; Kurkure, P

    2015-01-01

    Survivors of childhood cancer are at increased risk for several cardiometabolic complications. Obesity/overweight and metabolic syndrome have been widely reported in Western literature, but data from India are lacking. To perform an objective assessment of nutritional status in a cohort of childhood cancer survivors (CCSs) and to find risk factors for extremes in nutritional status. The study was a retrospective chart review of CCSs who attended the late effects clinic of a referral pediatric oncology center over the period of 1 year. An objective assessment of nutritional status was done, and results were analyzed in two groups: Adult survivors (present age <18 years) and child and adolescent survivors (CASs) (<18 years). The data were then analyzed for possible risk factors. Six hundred and forty-eight survivors were included in the study; of these, 471 were <18 years at follow-up, and 177 were 18 years or older. The prevalence of obesity, overweight, normal, and undernutrition was 2.6%, 10.8%, 62.7%, and 28.8% (CASs) and 0%, 8.5%, 62.7%, and 28.8% (adult survivors), respectively. Factors predictive of overweight/obesity were an initial diagnosis of acute lymphoblastic leukemia, or brain tumor and follow-up duration of >20 years or current age >30 years in adult survivors. The prevalence of obesity/overweight is lower in our cohort when compared to Western literature. It remains to be clarified whether this reflects the underlying undernutrition in our country, or whether our cohort of survivors is indeed distinct from their Western counterparts. Comparison with age/sex-matched normal controls and baseline parameters would yield more meaningful results.

  15. Mechanical memory

    DOEpatents

    Gilkey, Jeffrey C.; Duesterhaus, Michelle A.; Peter, Frank J.; Renn, Rosemarie A.; Baker, Michael S.

    2006-05-16

    A first-in-first-out (FIFO) microelectromechanical memory apparatus (also termed a mechanical memory) is disclosed. The mechanical memory utilizes a plurality of memory cells, with each memory cell having a beam which can be bowed in either of two directions of curvature to indicate two different logic states for that memory cell. The memory cells can be arranged around a wheel which operates as a clocking actuator to serially shift data from one memory cell to the next. The mechanical memory can be formed using conventional surface micromachining, and can be formed as either a nonvolatile memory or as a volatile memory.

  16. Mechanical memory

    DOEpatents

    Gilkey, Jeffrey C.; Duesterhaus, Michelle A.; Peter, Frank J.; Renn, Rosemarie A.; Baker, Michael S.

    2006-08-15

    A first-in-first-out (FIFO) microelectromechanical memory apparatus (also termed a mechanical memory) is disclosed. The mechanical memory utilizes a plurality of memory cells, with each memory cell having a beam which can be bowed in either of two directions of curvature to indicate two different logic states for that memory cell. The memory cells can be arranged around a wheel which operates as a clocking actuator to serially shift data from one memory cell to the next. The mechanical memory can be formed using conventional surface micromachining, and can be formed as either a nonvolatile memory or as a volatile memory.

  17. Whole Neuraxis Irradiation to Address Central Nervous System Relapse in High-Risk Neuroblastoma

    SciTech Connect

    Croog, Victoria J.; Kramer, Kim; Cheung, Nai-Kong V.; Kushner, Brian H.; Modak, Shakeel; Souweidane, Mark M.; Wolden, Suzanne L.

    2010-11-01

    Background: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). Methods: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); one patient in the non-CSI cohort received IO-RIT. Results: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. Conclusions: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.

  18. Robotic Telecytology for Remote Cytologic Evaluation without an On-site Cytotechnologist or Cytopathologist: A Tale of Implementation and Review of Constraints

    PubMed Central

    Sirintrapun, Sahussapont Joseph; Rudomina, Dorota; Mazzella, Allix; Feratovic, Rusmir; Alago, William; Siegelbaum, Robert; Lin, Oscar

    2017-01-01

    Background: The first satellite center to offer interventional radiology procedures at Memorial Sloan Kettering Cancer Center opened in October 2014. Two of the procedures offered, fine needle aspirations and core biopsies, required rapid on-site cytologic evaluation of smears and biopsy touch imprints for cellular content and adequacy. The volume and frequency of such evaluations did not justify hiring on-site cytotechnologists, and therefore, a dynamic robotic telecytology (TC) solution was created. In this technical article, we present a detailed description of our implementation of robotic TC. Methods: Pathology devised the remote robotic TC solution after acknowledging that it would not be cost effective to staff cytotechnologists on-site at the satellite location. Sakura VisionTek was selected as our robotic TC solution. In addition to configuration of the dynamic robotic TC solution, pathology realized integrating the technology solution into operations would require a multidisciplinary effort and reevaluation of existing staffing and workflows. Results: Extensively described are the architectural framework and multidisciplinary process re-design, created to navigate the constraints of our technical, cultural, and organizational environment. Also reviewed are the benefits and challenges associated with available desktop sharing solutions, particularly accounting for information security concerns. Conclusions: Dynamic robotic TC is effective for immediate evaluations performed without on-site cytotechnology staff. Our goal is providing an extensive perspective of the implementation process, particularly technical, cultural, and operational constraints. Through this perspective, our template can serve as an extensible blueprint for other centers interested in implementing robotic TC without on-site cytotechnologists. PMID:28966832

  19. Impact of baseline visceral fat accumulation on prognosis in patients with metastatic renal cell carcinoma treated with systemic therapy.

    PubMed

    Mizuno, Ryuichi; Miyajima, Akira; Hibi, Taizo; Masuda, Aya; Shinojima, Toshiaki; Kikuchi, Eiji; Jinzaki, Masahiro; Oya, Mototsugu

    2017-04-01

    The aim of this study was to evaluate the clinical significance of visceral fat accumulation as a prognostic factor in patients with metastatic renal cell carcinoma (mRCC) treated with systemic therapies. A total of 114 patients were retrospectively reviewed. All patients received systemic therapy for mRCC at Keio University hospital in Japan. The intra-abdominal visceral fat area was determined by computed tomography at the umbilical level. The visceral fat accumulation was defined as ≥100 cm(2). The mean visceral fat area was 107.4 ± 62.8 cm(2). In the whole cohort, the median follow-up was 29 months. According to the Memorial Sloan Kettering Cancer Center (MSKCC) classification, 27.2% patients were favorable risk, 53.5% were intermediate risk, and 19.3% were poor risk. Visceral fat accumulation correlated with improved progression-free (P = 0.0070) and overall survival (P = 0.0001). On multivariate analysis, visceral fat accumulation (P = 0.0290) and MSKCC classification (P = 0.0085) were independent indices to predict progression-free survival in first-line treatment. In addition, visceral fat accumulation (P = 0.0007) and MSKCC classification (P = 0.0005) independently predicted overall survival. Prognostic grouping using visceral fat accumulation was identified as an independent prognostic marker in patients with mRCC. The addition of visceral fat accumulation improved the prognostic value of MSKCC classification alone in predicting overall survival in patients treated with systemic therapy for mRCC.

  20. Evaluating the effectiveness of a radiation safety training intervention for oncology nurses: a pretest – intervention – posttest study

    PubMed Central

    Dauer, Lawrence T; Kelvin, Joanne F; Horan, Christopher L; St Germain, Jean

    2006-01-01

    Background Radiation, for either diagnosis or treatment, is used extensively in the field of oncology. An understanding of oncology radiation safety principles and how to apply them in practice is critical for nursing practice. Misconceptions about radiation are common, resulting in undue fears and concerns that may negatively impact patient care. Effectively educating nurses to help overcome these misconceptions is a challenge. Historically, radiation safety training programs for oncology nurses have been compliance-based and behavioral in philosophy. Methods A new radiation safety training initiative was developed for Memorial Sloan-Kettering Cancer Center (MSKCC) adapting elements of current adult education theories to address common misconceptions and to enhance knowledge. A research design for evaluating the revised training program was also developed to assess whether the revised training program resulted in a measurable and/or statistically significant change in the knowledge or attitudes of nurses toward working with radiation. An evaluation research design based on a conceptual framework for measuring knowledge and attitude was developed and implemented using a pretest-intervention-posttest approach for 15% of the study population of 750 inpatient registered oncology nurses. Results As a result of the intervention program, there was a significant difference in nurse's cognitive knowledge as measured with the test instrument from pretest (58.9%) to posttest (71.6%). The evaluation also demonstrated that while positive nursing attitudes increased, the increase was significant for only 5 out of 9 of the areas evaluated. Conclusion The training intervention was effective for increasing cognitive knowledge, but was less effective at improving overall attitudes. This evaluation provided insights into the effectiveness of training interventions on the radiation safety knowledge and attitude of oncology nurses. PMID:16762060

  1. Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation.

    PubMed

    Weber, Daniela; Jenq, Robert R; Peled, Jonathan U; Taur, Ying; Hiergeist, Andreas; Koestler, Josef; Dettmer, Katja; Weber, Markus; Wolff, Daniel; Hahn, Joachim; Pamer, Eric G; Herr, Wolfgang; Gessner, André; Oefner, Peter J; van den Brink, Marcel R M; Holler, Ernst

    2017-02-14

    In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P < .001) and a decrease in fecal abundance of commensal Clostridiales (P = .03) compared with late antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P < .001). Timing of antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment.

  2. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment.

    PubMed

    D'Angelo, Sandra P; Shoushtari, Alexander N; Agaram, Narasimhan P; Kuk, Deborah; Qin, Li-Xuan; Carvajal, Richard D; Dickson, Mark A; Gounder, Mrinal; Keohan, Mary Louise; Schwartz, Gary K; Tap, William D

    2015-03-01

    The prognostic and predictive implications of programmed death-ligand 1 (PD-L1) is unknown in sarcoma. We sought to examine the immune milieu in sarcoma specimens. We evaluated PD-L1 expression by immunohistochemistry in sarcoma specimens and quantified tumor-infiltrating lymphocytes (TIL). We correlated expression with clinical parameters and outcomes. Fifty sarcoma patients treated at Memorial Sloan Kettering Cancer Center were selected. Using the DAKO PD-L1 immunohistochemistry assay and archival formalin-fixed paraffin-embedded tissue specimens; PD-L1 expression was examined. Macrophage and lymphocyte PD-L1 status was determined qualitatively. TIL was quantified. Associations between PD-L1 expression in tumor, macrophages and lymphocytes, TIL and clinical-pathological characteristics were performed. The median age was 46 years (range, 22-76), and 66% of patients were men. Tumor, lymphocyte and macrophage PD-L1 expression was noted in 12%, 30% and 58%, respectively, with the highest prevalence in gastrointestinal stromal tumors (29%). Lymphocyte and macrophage infiltration was present in 98% and 90%, respectively. There was no association between clinical features, overall survival and PD-L1 expression in tumor or immune infiltrates. Lymphocyte and macrophage infiltration is common in sarcoma, but PD-L1 tumor expression is uncommon in sarcoma with the highest frequency observed in gastrointestinal stromal tumors. There was no association between PD-L1 expression, TIL and clinicopathological features and overall survival; however, this is limited by the heterogenous patient sample and minimal death events in the studied cohort. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation

    SciTech Connect

    Peretz, T.; Nori, D.; Hilaris, B.; Manolatos, S.; Linares, L.; Harrison, L.; Anderson, L.L.; Fuks, Z.; Brennan, M.F. )

    1989-11-01

    Between January 1 1974 and October 31 1987, 98 patients with biopsy proven unresectable adenocarcinoma of the pancreas were treated with I-125 implants during laparotomy. Presenting symptoms were pain, jaundice, and weight loss. All patients underwent laparotomy and surgical staging. Thirty patients had T1NoMo disease, 47 patients had T2-3NoMo disease, and 21 patients had significant regional lymph node involvement (T1-3N1Mo). The surgical procedure performed was biopsy only (16 patients), gastric bypass, biliary bypass, and partial or total pancreatectomy with incomplete resection. The total activity and the number of seeds used were determined from the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Stereoshift localization X ray films were taken 3-6 days after operation. The mean activity, minimal peripheral dose (MPD), and volume of the implants were 35 mCi, 13,660 cGy, and 53 cm3, respectively. In addition, 27 patients received postoperative external irradiation and 27 patients received chemotherapy. Postoperative complications were observed in 19 patients. These included post-operative death (1 patient), biliary fistula (4), intraabdominal abscess (4), GI bleeding (3), gastric or small bowel obstruction (6), sepsis (5), and deep vein thrombophlebitis (4). Pain relief was obtained in 37/57 patients (65%) presenting with pain. A multivariate analysis showed that four factors significantly affected survival: T stage, N stage, administration of chemotherapy, and more than 30% reduction in the size of the implant on follow-up films. The median survival for the entire group was 7 months. A subgroup of patients with T1No stage disease who received chemotherapy survived 18.5 months. The indications for I-125 seed implantation in unresectable carcinoma of the pancreas are discussed.

  4. Outcomes and Prognostic Variables in Adenoid Cystic Carcinoma of the Head and Neck: A Recent Experience

    SciTech Connect

    Gomez, Daniel R. Hoppe, Bradford S.; Wolden, Suzanne L.; Zhung, Joanne E.; Patel, Snehal G.; Kraus, Dennis H.; Shah, Jatin P.; Ghossein, Ronald A.; Lee, Nancy Y.

    2008-04-01

    Purpose: To analyze the recent experience of patients with adenoid cystic carcinoma treated with radiation therapy at Memorial Sloan-Kettering Cancer Center. Methods and Materials: From 1990 to 2004, a total of 59 patients with a diagnosis of primary adenoid cystic carcinoma of the head and neck received radiation therapy at our institution. The subsite distribution was oral cavity, 28% (n = 17); paranasal sinuses, 22% (n = 13); parotid, 14% (n = 8); submandibular, 14% (n = 8); oropharynx, 10% (n = 6); sublingual, 3% (n = 2); nasopharynx, 3% (n = 2); and other, 5% (n = 3). T Stage distribution was T1, 34% (n = 20); T2, 19% (n = 11); T3, 14% (n = 8); and T4, 34% (n = 20). Twenty-nine percent of patients (n = 17) were treated with intensity-modulated radiation therapy; 25% (n =15), with three-dimensional conformal therapy, and the remainder, with conventional techniques. Ninety percent (n = 53) of patients received treatment including the base of skull. Results: Median follow-up for surviving patients was 5.9 years. Five-year and 10-year rates of local control and distant metastases-free survival were 91%/81% and 81%/49%, respectively. Five-year and 10-year rates of disease-free and overall survival were 76%/40% and 87%/65%, respectively. On univariate analysis, stage T4 (p = 0.004) and gross/clinical nerve involvement (p = 0.002) were associated with decreased progression free survival, whereas stage T4 and lymph node involvement were associated with decreased overall survival (p = 0.046 and p < 0.001, respectively). Conclusions: Radiation therapy in combination with surgery produces excellent rates of local control, although distant metastases account for a high proportion of failures. Routine treatment to the base of skull reduces the significance of histologic perineural invasion, but major nerve involvement remains an adverse prognostic factor.

  5. Clinicopathological and prognostic factors for long-term survival in Chinese patients with metastatic renal cell carcinoma treated with sorafenib: a single-center retrospective study

    PubMed Central

    Wang, Hong-Kai; Gu, Wei-Jie; Ma, Chun-Guang; Shi, Guo-Hai; Zhou, Liang-Ping; Ye, Ding-Wei

    2015-01-01

    Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1–27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7–16.4) months at a median follow-up time of 61.8 (95% CI: 16.2–97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients. PMID:26472104

  6. The top 100 cited articles in urology: An update.

    PubMed

    Nason, Gregory J; Tareen, Farhan; Mortell, Alan

    2013-01-01

    In this paper, we identify and analyze the top 100 cited articles in urology since 1965 and assess changes in the top 100 since 2007. We selected highest impact journals in both urological and general medicine journals from the 2011 edition of Journal Citation Reports: Science edition. We identified and analyzed the 100 most cited articles using the Science Citation Index Expanded (1965-present). The top 100 articles were cited a mean of 892 times (range: 529-2088) and published between 1966 and 2009, with 21 published since 2000. In 2012, 19 new articles appeared in the updated top 100 cited articles. Also, 16 journals were represented, led by the New England Journal of Medicine (n=36), the Journal of Urology (n=16) and the Lancet (n=12). In total, 81 articles were published from North America (USA=77, Canada=4). From the United States, the following institutes were among the top 5 represented: Johns Hopkins University (n=12), Harvard University, Memorial Sloan Kettering Cancer Centre, National Institute of Health and Washington University (all 5). Only one institute outside the United States published more than one article in the top 100 (Institut Gustave Roussy, France). Nine urologists were first authors of 2 or more articles. Oncology (n=54) and transplantation (n=22) were the most common subspecialties represented. It is important to acknowledge the top cited articles as they mark key topics and advances in urology. There has been a 19% change in the top 100 cited articles in the past 5 years. Oncology and transplantation remain the most highly cited topics.

  7. Predicting Outcome in Patients with Rhabdomyosarcoma: Role of [{sup 18}F]Fluorodeoxyglucose Positron Emission Tomography

    SciTech Connect

    Casey, Dana L.; Wexler, Leonard H.; Fox, Josef J.; Dharmarajan, Kavita V.; Schoder, Heiko; Price, Alison N.; Wolden, Suzanne L.

    2014-12-01

    Purpose: To evaluate whether [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) response of the primary tumor after induction chemotherapy predicts outcomes in rhabdomyosarcoma (RMS). Methods and Materials: After excluding those with initial tumor resection, 107 patients who underwent FDG-PET after induction chemotherapy at Memorial Sloan Kettering Cancer Center from 2002 to 2013 were reviewed. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated according to FDG-PET response and maximum standardized uptake value (SUV) at baseline (PET1/SUV1), after induction chemotherapy (PET2/SUV2), and after local therapy (PET3/SUV3). Receiver operator characteristic curves were used to determine the optimal cutoff for dichotomization of SUV1 and SUV2 values. Results: The SUV1 (<9.5 vs ≥9.5) was predictive of PFS (P=.02) and OS (P=.02), but not LC. After 12 weeks (median) of induction chemotherapy, 45 patients had negative PET2 scans and 62 had positive scans: 3-year PFS was 72% versus 44%, respectively (P=.01). The SUV2 (<1.5 vs ≥1.5) was similarly predictive of PFS (P=.005) and was associated with LC (P=.02) and OS (P=.03). A positive PET3 scan was predictive of worse PFS (P=.0009), LC (P=.05), and OS (P=.03). Conclusions: [{sup 18}F]fluorodeoxyglucose positron emission tomography is an early indicator of outcomes in patients with RMS. Future prospective trials may incorporate FDG-PET response data for risk-adapted therapy and early assessment of new treatment regimens.

  8. Psychosocial and Sexual Well-Being Following Nipple-Sparing Mastectomy and Reconstruction

    PubMed Central

    Wei, Cindy H.; Scott, Amie M.; Price, Alison N.; Miller, H. Catherine; Klassen, Anne F.; Jhanwar, Sabrina M.; Mehrara, Babak J.; Disa, Joseph J.; McCarthy, Colleen; Matros, Evan; Cordeiro, Peter G.; Sacchini, Virgilio; Pusic, Andrea L.

    2016-01-01

    Background Nipple-sparing mastectomy (NSM) is considered an oncologically safe option for select patients. As many patients are candidates for nipple-sparing or skin-sparing mastectomy (SSM), reliable patient-reported outcome data are crucial for decision-making. The objective of this study was to determine whether patient satisfaction and/or health-related quality of life (HRQOL) were improved by preservation of the nipple with NSM compared to SSM and nipple reconstruction. Methods Subjects were identified from a prospectively maintained database of patients who completed the BREAST-Q following mastectomy and breast reconstruction between March and October 2011 at Memorial Sloan Kettering Cancer Center. Fifty-two patients underwent NSM followed by immediate expander-implant reconstruction. A comparison group consisted of 202 patients who underwent SSM followed by immediate expander-implant reconstruction and later nipple reconstruction. HRQOL and satisfaction domains as measured by BREAST-Q scores were compared in multivariate linear regression analyses that controlled for potential confounding factors. Results NSM patients reported significantly higher scores in the psychosocial (p=0.01) and sexual well-being (p=0.02) domains compared to SSM patients. There was no significant difference in the BREAST-Q physical well-being, satisfaction with breast, or satisfaction with outcome domains between the NSM and SSM groups. Conclusions NSM is associated with higher psychosocial and sexual well-being compared to SSM and nipple reconstruction. Preoperative discussion of such HRQOL outcomes with patients may facilitate informed decision-making and realistic postoperative expectations. PMID:26782950

  9. Psychosocial and Sexual Well-Being Following Nipple-Sparing Mastectomy and Reconstruction.

    PubMed

    Wei, Cindy H; Scott, Amie M; Price, Alison N; Miller, Helen Catherine; Klassen, Anne F; Jhanwar, Sabrina M; Mehrara, Babak J; Disa, Joseph J; McCarthy, Colleen; Matros, Evan; Cordeiro, Peter G; Sacchini, Virgilio; Pusic, Andrea L

    2016-01-01

    Nipple-sparing mastectomy (NSM) is considered an oncologically safe option for select patients. As many patients are candidates for nipple-sparing or skin-sparing mastectomy (SSM), reliable patient-reported outcome data are crucial for decision-making. The objective of this study was to determine whether patient satisfaction and/or health-related quality of life (HRQOL) were improved by preservation of the nipple with NSM compared to SSM and nipple reconstruction. Subjects were identified from a prospectively maintained database of patients who completed the BREAST-Q following mastectomy and breast reconstruction between March and October 2011 at Memorial Sloan Kettering Cancer Center. Fifty-two patients underwent NSM followed by immediate expander-implant reconstruction. A comparison group consisted of 202 patients who underwent SSM followed by immediate expander-implant reconstruction and later nipple reconstruction. HRQOL and satisfaction domains as measured by BREAST-Q scores were compared in multivariate linear regression analyzes that controlled for potential confounding factors. NSM patients reported significantly higher scores in the psychosocial (p = 0.01) and sexual well-being (p = 0.02) domains compared to SSM patients. There was no significant difference in the BREAST-Q physical well-being, satisfaction with breast, or satisfaction with outcome domains between the NSM and SSM groups. NSM is associated with higher psychosocial and sexual well-being compared to SSM and nipple reconstruction. Preoperative discussion of such HRQOL outcomes with patients may facilitate informed decision-making and realistic postoperative expectations. © 2015 Wiley Periodicals, Inc.

  10. Contrast Media Use in Radiation Oncology: A Prospective, Controlled Educational Intervention Study with Retrospective Analysis of Patient Outcomes

    PubMed Central

    Barker, Christopher A.; Mutter, Robert W.; Shapiro, Lauren Q.; Zhang, Zhigang; Wolden, Suzanne L.; Yahalom, Joachim

    2016-01-01

    Purpose Intravenous contrast media (ICM) administration is recommended as part of radiation therapy (RT) simulation in a variety of clinical scenarios, but can cause adverse events. We sought to assess radiation oncology resident knowledge about ICM, and to determine if an educational intervention (EI) could improve this level of knowledge. In conjunction, we retrospectively analyzed risk factors and adverse events related to ICM use before and after the EI to determine whether any improvements in patient outcomes could be realized. Methods Over 2 years, 21 residents in radiation oncology at Memorial Sloan-Kettering Cancer Center (MSKCC) participated in a pretest-EI-posttest study based on the ACR’s Manual on Contrast Media. Medical and RT records were reviewed, and ICM use, risk factors and adverse events were recorded. Results There was no significant difference in resident understanding of ICM use in residents of different years of training (p=0.85). Understanding of ICM use increased in residents that attended the EI (p<0.05), but this was not sustained 1 year after the EI (p=0.48). Of the 6852 RT simulations that were performed at MSKCC, 1350 (19.7%) involved ICM. Mild adverse events occurred in a few patients (<5%) simulated with ICM, but there was no difference in the number of risk factors or adverse events before and after the EI. Conclusions The EI effectively improved short-term understanding of ICM use. However, the effect was not sustained. The frequency of adverse events related to ICM use was small and not significantly impacted by the EI. PMID:21129689

  11. Development of a Metabolomic Radiation Signature in Urine from Patients Undergoing Total Body Irradiation

    PubMed Central

    Laiakis, Evagelia C.; Mak, Tytus D.; Anizan, Sebastien; Amundson, Sally A.; Barker, Christopher A.; Wolden, Suzanne L.; Brenner, David J.; Fornace, Albert J.

    2014-01-01

    The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4–6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher’s exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid β-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker

  12. Everolimus in patients with metastatic renal cell carcinoma previously treated with bevacizumab: a prospective multicenter study CRAD001LRU02T.

    PubMed

    Tsimafeyeu, Ilya; Snegovoy, Anton; Varlamov, Sergei; Safina, Sufia; Varlamov, Ilya; Gurina, Ludmila; Manzuk, Ludmila

    2015-09-01

    Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR) recommended for patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor (VEGF) receptor-tyrosine kinase inhibitor therapy. Efficacy of everolimus in patients who progressed on anti-VEGF monoclonal antibody bevacizumab is unknown. We did a multicenter prospective trial of everolimus in patients with mRCC whose disease had progressed on bevacizumab ± interferon alpha (IFN). Patients with clear-cell mRCC which had progressed on bevacizumab ± IFN received everolimus 10 mg once daily. The primary end point was the proportion of patients remaining progression-free for 56 days, and a two-stage Simon design was used, with 80% power and an alpha risk of 5%. This study is registered with ClinicalTrials.gov, number NCT02056587. From December 2011 to October 2013, a total of 37 patients (28 M, 9 F) were enrolled. Median age was 60.5 years (range 41-66), 1% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) >2, and Memorial Sloan-Kettering Cancer Center (MSKCC) favorable/intermediate risk was 38/62%. Five (14%) patients had a confirmed partial response and 26 (70%) patients had a stable disease. Median progression-free survival was 11.5 months (95% CI, 8.8-14.2). Median overall survival was not reached. No grade 3 or 4 treatment-related toxicities were observed. The most common grade 2 adverse events were fatigue (19%) and pneumonitis (8%). Everolimus demonstrated a favorable toxicity profile and promising anti-tumor activity as a second-line therapy in metastatic renal cell carcinoma (RCC) patients previously treated with bevacizumab ± IFN.

  13. Handheld Reflectance Confocal Microscopy for the Detection of Recurrent Extramammary Paget Disease.

    PubMed

    Yélamos, Oriol; Hibler, Brian P; Cordova, Miguel; Hollmann, Travis J; Kose, Kivanc; Marchetti, Michael A; Myskowski, Patricia L; Pulitzer, Melissa P; Rajadhyaksha, Milind; Rossi, Anthony M; Jain, Manu

    2017-07-01

    Extramammary Paget disease (EMPD) is commonly refractory to surgical and nonsurgical therapies. Identifying recurrent or persistent EMPD is challenging because the disease is multifocal, and multiple blind scouting biopsies are usually performed in this setting. Handheld reflectance confocal microscopy (HRCM) has been used to diagnose and map primary EMPD and therefore may be used to identify EMPD recurrences. To evaluate HRCM's diagnostic accuracy in the setting of recurrent or persistent EMPD as well as its potential diagnostic pitfalls. This prospective case series study included patients referred to the Dermatology Service at Memorial Sloan Kettering Cancer Center between January 1, 2014, and December 31, 2016, with biopsy-proven EMPD in whom HRCM was used to monitor treatment response. Five patients were included, and 22 sites clinically concerning for recurrent or persistent disease were evaluated using HRCM and histopathologic examination. In 2 patients, video mosaics were created to evaluate large areas. Sensitivity and specificity of HRCM in identifying recurrent or persistent EMPD; causes for false-negative results according to their location, histopathologic findings, and previous treatments. Of the 22 clinically suspicious sites evaluated in 5 patients (4 men, 1 woman; median [range] age, 70 [56-77] years), 9 (40.9%) were positive for recurrent disease on HRCM and histopathologically confirmed, and 13 (59.1%) sites were negative on HRCM, but 3 of the 13 were positive for EMPD on histopathological examination. In general, HRCM had a sensitivity of 75% and a specificity of 100% in identifying recurrent or persistent EMPD. False-negative results were found in 2 patients and occurred at the margins of EMPD, close to previous biopsy sites. Creating video mosaics (or video mosaicking) seemed to improve the detection of EMPD. Handheld reflectance confocal microscopy is a useful auxiliary tool for diagnosing EMPD recurrences and can be used to guide scouting

  14. Parameningeal rhabdomyosarcoma (including the orbit): results of orbital irradiation

    SciTech Connect

    Jereb, B.; Haik, B.G.; Ong, R.; Ghavimi, F.

    1985-12-01

    Twenty-three patients with parameningeal (including orbital rhabdomyosarcoma (RMS)) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1971 and January 1983. Twenty were children with a mean age of 6 and 3 were adults. In 6 patients, the primary tumor was from the orbit, whereas the remaining 17 had other parameningeal primary sites. The tumors were in a very progressive local stage, with extensive destruction of the facial bones in 19 patients. Eight patients were treated with T2 chemotherapy protocol and 15 received T6. Seven patients received 5,000 to 7,200 rad delivered to the primary tumor in 11-16 weeks, 15 patients received between 4,500 to 5,000 rad in 4-7 weeks, and 1 patient received 3,000 rad in 3 weeks for residual microscopic disease following surgery. Two patients were treated with radiation to the whole brain; no patients received radiation of the whole central nervous axis (CNA). Fifteen of the 23 patients (65%) are alive and well with a medical follow-up time of 5 years. Two patients died of therapeutic complications and six died of tumor spread. In five patients, involvement of the central nervous system (CNS) was the cause of death. The prognosis of orbital RMS with parameningeal involvement is no better than in other tumors of parameningeal sites. In those patients who had impaired vision because of optic nerve damage prior to treatment, the vision did not improve following treatment. There was no impaired vision seen due to radiation damage of eye structures except in the lens.

  15. Long-term benefit of sunitinib in patients with metastatic renal cell carcinoma in Latin America: retrospective analysis of patient clinical characteristics.

    PubMed

    Smaletz, Oren; Chacón, Matias; de Oliveira Koch, Ludmila; de Carvalho Rocha, Daniela R; Cardoso, Fernanda C

    2016-01-01

    To describe the clinical characteristics of Latin American patients with metastatic renal cell carcinoma (mRCC) who experienced a progression-free survival (PFS) for at least 15 months following treatment with sunitinib. In this retrospective analysis, mRCC patients in two institutions in Latin America received sunitinib at a starting dose of either 50 mg/day for 4 weeks followed by 2 weeks off treatment (Schedule 4/2) in repeated 6-week cycles or sunitinib 37.5 mg on a continuous daily dosing schedule. Clinical characteristics, tolerability, and PFS data were collected. Twenty-nine patients with long-term clinical benefit from sunitinib were identified between September 2005 and August 2009. Median PFS was 23 months (range: 15-54 months). Two of the 29 patients with prolonged PFS achieved a complete response and additional eleven had a partial response. Most patients were aged <60 years, had good performance status, favorable or intermediate Memorial Sloan Kettering Cancer Center prognostic risk, and disease limited to one or two sites. Dose reduction was necessary in all patients who started sunitinib at 50 mg/day administered on Schedule 4/2. Adverse events leading to dose reduction included grade 3 hand-foot syndrome, mucositis, fatigue, and hypertension. At the time of data cutoff, four patients were still receiving sunitinib treatment. Extended PFS can be achieved in Latin American patients with mRCC treated with sunitinib. Although the small sample size and retrospective nature of this evaluation preclude the identification of pretreatment predictive factors contributing to this benefit, the current analysis warrants further investigation using a larger data set in this population.

  16. SU-E-T-502: Initial Results of a Comparison of Treatment Plans Produced From Automated Prioritized Planning Method and a Commercial Treatment Planning System

    SciTech Connect

    Tiwari, P; Chen, Y; Hong, L; Apte, A; Yang, J; Mechalakos, J; Mageras, G; Hunt, M; Deasy, J

    2015-06-15

    Purpose We developed an automated treatment planning system based on a hierarchical goal programming approach. To demonstrate the feasibility of our method, we report the comparison of prostate treatment plans produced from the automated treatment planning system with those produced by a commercial treatment planning system. Methods In our approach, we prioritized the goals of the optimization, and solved one goal at a time. The purpose of prioritization is to ensure that higher priority dose-volume planning goals are not sacrificed to improve lower priority goals. The algorithm has four steps. The first step optimizes dose to the target structures, while sparing key sensitive organs from radiation. In the second step, the algorithm finds the best beamlet weight to reduce toxicity risks to normal tissue while holding the objective function achieved in the first step as a constraint, with a small amount of allowed slip. Likewise, the third and fourth steps introduce lower priority normal tissue goals and beam smoothing. We compared with prostate treatment plans from Memorial Sloan Kettering Cancer Center developed using Eclipse, with a prescription dose of 72 Gy. A combination of liear, quadratic, and gEUD objective functions were used with a modified open source solver code (IPOPT). Results Initial plan results on 3 different cases show that the automated planning system is capable of competing or improving on expert-driven eclipse plans. Compared to the Eclipse planning system, the automated system produced up to 26% less mean dose to rectum and 24% less mean dose to bladder while having the same D95 (after matching) to the target. Conclusion We have demonstrated that Pareto optimal treatment plans can be generated automatically without a trial-and-error process. The solver finds an optimal plan for the given patient, as opposed to database-driven approaches that set parameters based on geometry and population modeling.

  17. Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines

    PubMed Central

    Romano, Emanuela; Scordo, Michael; Dusza, Stephen W.; Coit, Daniel G.; Chapman, Paul B.

    2010-01-01

    Purpose Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based. Patients and Methods Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period. Results The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse. Conclusion Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses. PMID:20479405

  18. Central nervous system involvement in T-cell lymphoma: A single center experience.

    PubMed

    Gurion, Ronit; Mehta, Neha; Migliacci, Jocelyn C; Zelenetz, Andrew; Moskowitz, Alison; Lunning, Matthew; Moskowitz, Craig; Hamlin, Paul; Horwitz, Steven

    2016-05-01

    Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

  19. Guidelines for locoregional therapy in primary breast cancer in developing countries: The results of an expert panel at the 8th Annual Women's Cancer Initiative – Tata Memorial Hospital (WCI-TMH) Conference

    PubMed Central

    Munshi, Anusheel; Gupta, Sudeep; Anderson, Benjamin; Yarnold, John; Parmar, Vani; Jalali, Rakesh; Sharma, Suresh Chander; Desai, Sangeeta; Thakur, Meenakshi; Baijal, Gunjan; Sarin, Rajiv; Mittra, Indraneel; Ghosh, Jaya; Badwe, Rajendra

    2012-01-01

    Background: Limited guidelines exist for breast cancer management in developing countries. In this context, the Women's Cancer Initiative - Tata Memorial Hospital (WCI-TMH) organised its 8th Annual Conference to update guidelines in breast cancer. Materials and Methods: Appropriately formulated guideline questions on each topic and subtopic in the surgical, radiation and systemic management of primary breast cancer were developed by the scientific committee and shared with the guest faculty of the Conference. Majority of the questions had multiple choice answers. The opinion of the audience, comprising academic and community oncologists, was electronically cumulated, followed by focussed presentations by eminent national and international experts on each topic. The guidelines were finally developed through an expert panel that voted on each guideline question after all talks had been delivered and audience opinion elicited. Separate panels were constituted for locoregional and systemic therapy in primary breast cancer. Results: Based on the voting results of the expert panel, guidelines for locoregional therapy of breast cancer have been formulated. Voting patterns for each question are reported. Conclusions: The updated guidelines on locoregional management of primary breast cancer in the context of developing countries are presented in this article. These recommendations have been designed to allow centers in the developing world to improve the quality of care for breast cancer patients. PMID:22988354

  20. Memorial symptom assessment scale.

    PubMed

    Chang, Victor T; Hwang, Shirley S; Thaler, Howard T; Kasimis, Basil S; Portenoy, Russell K

    2004-04-01

    Patients with advanced illnesses often have multiple symptoms. As interest in palliative care and interventions for symptom control increase, the ability to assess multiple symptoms has become more important. A number of instruments have been developed to meet this need in cancer patients. This article reviews the development and applications of a multidimensional instrument, the Memorial Symptom Assessment Scale. The Memorial Symptom Assessment Scale has 32 symptoms and three dimensions of frequency, severity, and distress. Shorter versions - The Memorial Symptom Assessment Scale Short Form (32 symptoms with one dimension) and the Condensed Memorial Symptom Assessment Scale (14 symptoms with one dimension), and a version for children aged 7-12 years, have also been developed. A distinctive feature is the summary subscales for physical distress, psychological distress, and The Global Distress Index. The Memorial Symptom Assessment Scale has proven useful in description of symptom epidemiology, the role of symptoms in pain, fatigue, and spirituality; as a predictor of survival, and in proxy assessments of pain. The Memorial Symptom Assessment Scale has been used in studies of cancer and AIDS patients, and patients with advanced medical illnesses. Possible future roles of instruments such as the Memorial Symptom Assessment Scale include use in clinical trials, for pharmacoeconomic analyses, definition of symptom clusters and symptom burden, the development of symptom outcome measures, symptom monitoring, and improving care for patients. Continued research is needed for the versions of the Memorial Symptom Assessment Scale and other symptom instruments in different populations and applications.

  1. Zfra activates memory Hyal-2+ CD3− CD19− spleen cells to block cancer growth, stemness, and metastasis in vivo

    PubMed Central

    Chang, Jean-Yun; Huang, Shenq-Shyang; Chou, Pei-Yi; Ye, Siou-Ru; Chen, Szu-Jung; He, Huan; Liu, Ting-Hsiu; Chou, Ying-Tsen; Lai, Feng-Jie; Chen, Shean-Jen; Lee, Hoong-Chien; Kakhniashvili, David; Goodman, Steven R.; Chang, Nan-Shan

    2015-01-01

    Zfra is a 31-amino-acid zinc finger-like protein, which participates in the tumor necrosis factor signaling. Here, we determined that when nude mice and BALB/c mice were pre-injected with nanogram levels of a synthetic Zfra1–31 or truncated Zfra4–10 peptide via tail veins, these mice became resistant to the growth, metastasis and stemness of melanoma cells, and many malignant cancer cells. The synthetic peptides underwent self-polymerization in phosphate-buffered saline. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra aggregation and its-mediated cancer suppression in vivo. Injected Zfra peptide autofluoresced due to polymerization and was trapped mainly in the spleen. Transfer of Zfra-stimulated spleen cells to naïve mice conferred resistance to cancer growth. Zfra-binding cells, designated Hyal-2+ CD3− CD19− Z cells, are approximately 25–30% in the normal spleen, but are significantly downregulated (near 0–3%) in tumor-growing mice. Zfra prevented the loss of Z cells caused by tumors. In vitro stimulation or education of naïve spleen cells with Zfra allowed generation of activated Z cells to confer a memory anticancer response in naïve or cancer-growing mice. In particular, Z cells are abundant in nude and NOD-SCID mice, and can be readily activated by Zfra to mount against cancer growth. PMID:25686832

  2. CD20+ T cells have a predominantly Tc1 effector memory phenotype and are expanded in the ascites of patients with ovarian cancer

    PubMed Central

    de Bruyn, Marco; Wiersma, Valerie R; Wouters, Maartje C A; Samplonius, Douwe F; Klip, Harry G; Helfrich, Wijnand; Nijman, Hans W; Eggleton, Paul; Bremer, Edwin

    2015-01-01

    Recently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20 molecules are transferred to the cell surface of T cells by trogocytosis together with the established trogocytosis marker HLA-DR. Further, the presence of CD20 on isolated CD20+ T cells remained stable for up to 48h of ex vivo culture. These CD20+ T cells almost exclusively produced IFNγ (∼70% vs. ∼20% in the CD20− T cell population) and were predominantly (CD8+) effector memory T cells (∼60–70%). This IFNγ producing and effector memory phenotype was also determined for CD20+ T cells as detected in the peripheral blood and ascitic fluids of ovarian cancer (OC) patients. In the latter, the percentage of CD20+ T cells was further strongly increased (from ∼6% in peripheral blood to 23% in ascitic fluid). Taken together, the data presented here indicate that CD20 is transferred to T cells upon intimate T cell/B cell interaction. Further, CD20+ T cells are of memory and IFNγ producing phenotype and are present in increased amounts in ascitic fluid of OC patients. PMID:26137418

  3. MEMORY MODULATION

    PubMed Central

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  4. Memory Matters

    MedlinePlus

    ... different parts. Some of them are important for memory. The hippocampus (say: hih-puh-KAM-pus) is one of the more important parts of the brain that processes memories. Old information and new information, or memories, are ...

  5. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

    PubMed

    Cooke, Gillian E; Wetter, Nathan C; Banducci, Sarah E; Mackenzie, Michael J; Zuniga, Krystle E; Awick, Elizabeth A; Roberts, Sarah A; Sutton, Brad P; McAuley, Edward; Kramer, Arthur F

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

  6. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors

    PubMed Central

    Cooke, Gillian E.; Wetter, Nathan C.; Banducci, Sarah E.; Mackenzie, Michael J.; Zuniga, Krystle E.; Awick, Elizabeth A.; Roberts, Sarah A.; Sutton, Brad P.; McAuley, Edward; Kramer, Arthur F.

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment. PMID:26915025

  7. Memory Palaces

    ERIC Educational Resources Information Center

    Wood, Marianne

    2007-01-01

    This article presents a lesson called Memory Palaces. A memory palace is a memory tool used to remember information, usually as visual images, in a sequence that is logical to the person remembering it. In his book, "In the Palaces of Memory", George Johnson calls them "...structure(s) for arranging knowledge. Lots of connections to language arts,…

  8. The psychometric properties of the Hebrew version of the Memorial Symptom Assessment scale (MSAS-Heb) in patients with breast cancer.

    PubMed

    Pud, Dorit

    2015-04-01

    To date, no report of the psychometric properties of the Hebrew version of the Memorial Symptom Assessment Scale (MSAS-Heb) has been available, which may be a barrier to comprehensively assessing symptom frequency, severity, and distress in Israeli patients with cancer. This study aimed to translate the MSAS into Hebrew and to evaluate the psychometric properties in Israeli patients with cancer. The original 32-item MSAS was translated into Hebrew using the forward and backward procedure, and administered to female patients with early stage breast cancer (stages I-IIIA) who had received adjuvant chemotherapy. In addition, patients completed a demographic questionnaire, the Lee Fatigue Scale, the Center for Epidemiological Studies-Depression Scale, the General Sleep Disturbance Scale, a numeric rating scale for pain intensity, the Multidimensional Quality of Life Scale-Cancer and the Karnofsky Performance Status Scale. A sample of 110 patients was recruited (mean age 45.5 ± 10.1 years). The most frequent symptoms were hair loss (96.4%), lack of energy (88.2%) and "I do not look like myself" (80.9%), and the most infrequent were vomiting (7.3%), problems with urination (10.9%), and shortness of breath (20.9%). Cronbach alpha coefficients for the MSAS-Heb subscales (i.e., physical, psychological and global distress index) ranged from 0.78 to 0.90. All MSAS-Heb subscales and all the other questionnaires used in this study were significantly correlated (P < 0.0001), with expected directions. The MSAS-Heb is a valid and a reliable measure and should be a useful tool in the clinical arena and in future studies for evaluation of multiple symptoms in Israeli patients with cancer. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  9. Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer.

    PubMed Central

    Jordan, V. C.

    1993-01-01

    Tamoxifen has been found to be a safe and effective treatment for all stages of breast cancer. Long term tamoxifen therapy is associated with some rare, but potentially serious, side effects so patients should be carefully monitored. However, long term tamoxifen therapy is also associated with a number of physiological benefits over and above its tumouristatic action. These benefits include a decrease in the development of contralateral breast cancer, the maintenance of bone density in postmenopausal women and a decrease in cardiovascular disease. The successful application of tamoxifen to treat breast cancer has increased enthusiasm to test its worth to prevent breast cancer. Although there are individual requests by patients for tamoxifen to prevent breast cancer, individual treatment is inappropriate. Tamoxifen can only be adequately evaluated as a preventive in randomized, double-blind clinical trials. These trials are in place and physicians should encourage women to participate and establish a new therapeutic option as rapidly as possible. PMID:8242225

  10. Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients.

    PubMed

    Casati, Anna; Varghaei-Nahvi, Azam; Feldman, Steven Alexander; Assenmacher, Mario; Rosenberg, Steven Aaron; Dudley, Mark Edward; Scheffold, Alexander

    2013-10-01

    The adoptive transfer of lymphocytes genetically engineered to express tumor-specific antigen receptors is a potent strategy to treat cancer patients. T lymphocyte subsets, such as naïve or central memory T cells, selected in vitro prior to genetic engineering have been extensively investigated in preclinical mouse models, where they demonstrated improved therapeutic efficacy. However, so far, this is challenging to realize in the clinical setting, since good manufacturing practices (GMP) procedures for complex cell sorting and genetic manipulation are limited. To be able to directly compare the immunological attributes and therapeutic efficacy of naïve (T(N)) and central memory (T(CM)) CD8(+) T cells, we investigated clinical-scale procedures for their parallel selection and in vitro manipulation. We also evaluated currently available GMP-grade reagents for stimulation of T cell subsets, including a new type of anti-CD3/anti-CD28 nanomatrix. An optimized protocol was established for the isolation of both CD8(+) T(N) cells (CD4(-)CD62L(+)CD45RA(+)) and CD8(+) T(CM) (CD4(-)CD62L(+)CD45RA(-)) from a single patient. The highly enriched T cell subsets can be efficiently transduced and expanded to large cell numbers, sufficient for clinical applications and equivalent to or better than current cell and gene therapy approaches with unselected lymphocyte populations. The GMP protocols for selection of T(N) and T(CM) we reported here will be the basis for clinical trials analyzing safety, in vivo persistence and clinical efficacy in cancer patients and will help to generate a more reliable and efficacious cellular product.

  11. Memory Matters

    MedlinePlus

    ... blood vessel (which carries the blood) bursts. continue Brain Injuries Affect Memory At any age, an injury to ... with somebody's memory. Some people who recover from brain injuries need to learn old things all over again, ...

  12. Class II transactivator-induced MHC class II expression in pancreatic cancer cells leads to tumor rejection and a specific antitumor memory response.

    PubMed

    Ekkirala, Chaitanya Ramesh; Cappello, Paola; Accolla, Roberto S; Giovarelli, Mirella; Romero, Irene; Garrido, Cristina; Garcia-Lora, Angel Miguel; Novelli, Francesco

    2014-10-01

    The loss of major histocompatibility complex (MHC) classes I and II is a well-known mechanism by which cancer cells are able to escape from immune recognition. In this study, we analyzed the expression of antigen processing and presenting molecules in 2 cell lines derived from mouse models of pancreatic ductal adenocarcinoma (PDA) and the effects of the re-expression of MHC class II on PDA rejection. The PDA cell lines were analyzed for the expression of MHC class I, II, and antigen-processing molecules by flow cytometry or polymerase chain reaction. We generated stable PDA-MHC class II transactivator (CIITA) cells and injected them into syngeneic mice. The CD4 and CD8 T-cell role was analyzed in vitro and in vivo. Murine PDA cell lines were negative for MHC and antigen-processing molecules, but their expression was restored by exogenous interferon-γ. CIITA-tumor cells were rejected in 80% to 100% of injected mice, which also developed long-lasting immune memory. In vitro assays and immunohistochemical analyses revealed the recruitment of T effector cells and CD8 T cells into the tumor area. Overall, these data confirm that immunotherapy is a feasible therapeutic approach to recognize and target an aggressive cancer such as PDA.

  13. Memory Dysfunction

    PubMed Central

    Matthews, Brandy R.

    2015-01-01

    Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

  14. Gregorius Agricola memorial lecture: Lung cancer-A work-related disease for 500 years, as predicted by Agricola.

    PubMed

    Langård, Sverre

    2015-01-01

    In the early 16th century Gregorius Agricola reported on Bergsucht (miner's consumption) in mine workers in the Erzgebirge. About 350 years later, Härting and Hesse reported on large numbers of lung cancers among the mine-workers in the same mine district, thus confirming that Bergsucht primarily was lung cancer, but could also have been pnumoconiosis or tuberculosis or a combination of both. Mining for bismuth continued another 75 years--through World War II. Bismuth mining was replaced by large scale uranium mining from the late 1940 through 1989, employing some 400-450,000 workers, resulting in the major local epidemic of work-related cancer larger than anywhere in the world, so far amounting to ± 14-15,000 cases. Had the mine developers listened to the warnings by Agricola and Härting and Hesse, the epidemic could have been prevented.

  15. Emerging memories

    NASA Astrophysics Data System (ADS)

    Baldi, Livio; Bez, Roberto; Sandhu, Gurtej

    2014-12-01

    Memory is a key component of any data processing system. Following the classical Turing machine approach, memories hold both the data to be processed and the rules for processing them. In the history of microelectronics, the distinction has been rather between working memory, which is exemplified by DRAM, and storage memory, exemplified by NAND. These two types of memory devices now represent 90% of all memory market and 25% of the total semiconductor market, and have been the technology drivers in the last decades. Even if radically different in characteristics, they are however based on the same storage mechanism: charge storage, and this mechanism seems to be near to reaching its physical limits. The search for new alternative memory approaches, based on more scalable mechanisms, has therefore gained new momentum. The status of incumbent memory technologies and their scaling limitations will be discussed. Emerging memory technologies will be analyzed, starting from the ones that are already present for niche applications, and which are getting new attention, thanks to recent technology breakthroughs. Maturity level, physical limitations and potential for scaling will be compared to existing memories. At the end the possible future composition of memory systems will be discussed.

  16. Memory protection

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    Accidental overwriting of files or of memory regions belonging to other programs, browsing of personal files by superusers, Trojan horses, and viruses are examples of breakdowns in workstations and personal computers that would be significantly reduced by memory protection. Memory protection is the capability of an operating system and supporting hardware to delimit segments of memory, to control whether segments can be read from or written into, and to confine accesses of a program to its segments alone. The absence of memory protection in many operating systems today is the result of a bias toward a narrow definition of performance as maximum instruction-execution rate. A broader definition, including the time to get the job done, makes clear that cost of recovery from memory interference errors reduces expected performance. The mechanisms of memory protection are well understood, powerful, efficient, and elegant. They add to performance in the broad sense without reducing instruction execution rate.

  17. Declarative memory.

    PubMed

    Riedel, Wim J; Blokland, Arjan

    2015-01-01

    Declarative Memory consists of memory for events (episodic memory) and facts (semantic memory). Methods to test declarative memory are key in investigating effects of potential cognition-enhancing substances--medicinal drugs or nutrients. A number of cognitive performance tests assessing declarative episodic memory tapping verbal learning, logical memory, pattern recognition memory, and paired associates learning are described. These tests have been used as outcome variables in 34 studies in humans that have been described in the literature in the past 10 years. Also, the use of episodic tests in animal research is discussed also in relation to the drug effects in these tasks. The results show that nutritional supplementation of polyunsaturated fatty acids has been investigated most abundantly and, in a number of cases, but not all, show indications of positive effects on declarative memory, more so in elderly than in young subjects. Studies investigating effects of registered anti-Alzheimer drugs, cholinesterase inhibitors in mild cognitive impairment, show positive and negative effects on declarative memory. Studies mainly carried out in healthy volunteers investigating the effects of acute dopamine stimulation indicate enhanced memory consolidation as manifested specifically by better delayed recall, especially at time points long after learning and more so when drug is administered after learning and if word lists are longer. The animal studies reveal a different picture with respect to the effects of different drugs on memory performance. This suggests that at least for episodic memory tasks, the translational value is rather poor. For the human studies, detailed parameters of the compositions of word lists for declarative memory tests are discussed and it is concluded that tailored adaptations of tests to fit the hypothesis under study, rather than "off-the-shelf" use of existing tests, are recommended.

  18. The significance of nipple discharge of the male breast.

    PubMed

    Morrogh, Mary; King, Tari A

    2009-01-01

    Although male breast cancer typically presents as a palpable mass, failure to recognize the significance of other symptoms may lead to a delay in diagnosis. Here we present our experience with male patients presenting with a chief complaint of nipple discharge (ND). Using the ICD-9 code for "breast symptoms," we identified 2,319 patients without a current cancer diagnosis who presented to Memorial Sloan-Kettering Cancer Center for evaluation; 24 (1%) patients were male (1995-2005). Data were collected by retrospective review. Among 24 male patients presenting for evaluation, 14 (58%) presented with a chief complaint of ND, while the remaining 10 (42%) presented for evaluation of a palpable mass in the absence of ND. Among 14 patients presenting with ND, subsequent clinical breast examination identified a breast mass +/- nipple changes in 7 of 14 patients. In total, 8 of 14 (57%) patients had an underlying malignancy; two of seven patients with ND alone had DCIS (median interval from onset of ND to presentation 3 weeks, range 2-4 weeks), and six of seven patients with ND and a palpable mass had invasive disease (median interval between onset of ND and presentation 16 weeks, range 2-52). The remaining 10/24 patients presented with a painless palpable mass of whom 8 (80%) were found to have underlying invasive disease (median interval between onset of mass, and presentation was 4 weeks, range 2-20 weeks). All patients with invasive disease were node-positive. At 23.7 months median follow-up (range, 7.7-88.3 months), 14 of 16 cancer patients remain free of disease and two have died as a direct result of metastatic disease. The incidence of cancer among males presenting with ND was 57%. In the absence of additional clinical findings, ND may be a herald for early, non-invasive disease. Increased awareness of subtle features of malignancy may represent a window of opportunity for early diagnosis and improved outcomes for male breast cancer patients.

  19. Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

    PubMed

    Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark

    2016-01-01

    Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99

  20. Micro-Mini & Nano-Dosimetry & Innovative Technologies in Radiation Therapy (MMND&ITRO2016)

    NASA Astrophysics Data System (ADS)

    2017-01-01

    The biennial MMND (formerly MMD) - IPCT workshops, founded in collaboration with Memorial Sloan Kettering Cancer Center (MSKCC) in 2001, has become an important international multidisciplinary forum for the discussion of advanced dosimetric technology for radiation therapy quality assurance (QA) and space science, as well as advanced technologies for prostate cancer treatment. In more recent years, the interests of participants and the scope of the workshops have extended far beyond prostate cancer treatment alone to include all aspects of radiation therapy, radiation science and technology. We therefore decided to change the name in 2016 to Innovative Technologies in Radiation Oncology (ITRO). MMND ITRO 2016 was held on 26-31 January, 2016 at the beautiful Wrest Point Hotel in Hobart, Tasmania and attracted an outstanding international faculty and nearly 200 delegates from 18 countries (http://mmnditro2016.com/) The MMND 2016 program continued to cover advanced medical physics aspects of IMRT, IGRT, VMAT, SBRT, MRI LINAC, innovative brachytherapy, and synchrotron MRT. The demand for sophisticated real time and high temporal and spatial resolution (down to the submillimetre scale) dosimetry methods and instrumentation for end-to-end QA for these radiotherapy technologies is increasing. Special attention was paid to the contribution of advanced imaging and the application of nanoscience to the recent improvements in imaging and radiotherapy. The last decade has seen great progress in charged particle therapy technology which has spread throughout the world and attracted strong current interest in Australia. This demands a better understanding of the fundamental aspects of ion interactions with biological tissue and the relative biological effectiveness (RBE) of protons and heavy ions. The further development of computational and experimental micro-and nano-dosimetry for ions has important application in radiobiology based treatment planning and space radiation

  1. Sentinel Node Mapping Using Indocyanine Green and Near-infrared Fluorescence Imaging Technology for Uterine Malignancies: Preliminary Experience With the Da Vinci Xi System.

    PubMed

    Siesto, Gabriele; Romano, Fabrizio; Fiamengo, Barbara; Vitobello, Domenico

    2016-01-01

    Sentinel lymph node (SLN) mapping has emerged as the new frontier for the surgical staging of apparently early-stage cervical and endometrial cancer. Different colorimetric and radioactive tracers, alone and in combination, have been proposed with encouraging results. Fluorometric mapping using indocyanine green (ICG) appears to be a suitable and attractive alternative to provide reliable staging [1-4]. In this video, we present the technique of SLN mapping in 2 cases (1 endometrial and 1 cervical cancer, respectively) using ICG and the near-infrared technology provided by the newest Da Vinci Xi robotic system (Intuitive Surgical Inc., Sunnyvale, CA). Together we report the results of our preliminary experience on the first 20 cases performed. The new robotic Da Vinci Xi system was available at our institution since May 2015. Upon institutional review board/ethical committee approval, all consecutive patients with early-stage endometrial and cervical cancer who were judged suitable for robotic surgery have been enrolled for SLN mapping with ICG. We adopted the Memorial Sloan Kettering Cancer Center SLN algorithm; the tracer was delivered into the cervix in all cases. Four milliliters (1.25 mg/mL) of ICG was injected divided into the 3- and 9-o'clock positions of the cervix alone, with 1 mL deep into the stroma and 1 mL submucosally at the skin incision. Sentinel lymph nodes were examined with a protocol including both ultrastaging with immunohistochemistry [3] and 1-step nucleic acid amplification assay [5,6] under a parallel protocol of study. During the study period, 20 cases were managed; 14 and 6 patients had endometrial and cervical cancer, respectively. SLN was detected in all cases (20/20, 100%). Bilateral SLNs were detected in 17 of 20 (85.0%) cases. Based on preoperative and intraoperative findings, 13 (65.0%) patients received systematic pelvic lymphadenectomy after SLN mapping. Three (15.0%) patients had microscopic nodal metastases on SLN. No

  2. Protocol for a cluster randomised trial of a communication skills intervention for physicians to facilitate survivorship transition in patients with lymphoma

    PubMed Central

    Parker, Patricia A; Banerjee, Smita C; Matasar, Matthew J; Bylund, Carma L; Franco, Kara; Li, Yuelin; Levin, Tomer T; Jacobsen, Paul B; Astrow, Alan B; Leventhal, Howard; Horwitz, Steven; Kissane, David W

    2016-01-01

    Introduction Survivors of cancer often describe a sense of abandonment post-treatment, with heightened worry, uncertainty, fear of recurrence and limited understanding of what lies ahead. This study examines the efficacy of a communication skills training (CST) intervention to help physicians address survivorship issues and introduce a new consultation focused on the use of a survivorship care plan for patients with Hodgkin's lymphoma and diffuse large B-cell lymphoma. Methods and analysis Specifically, this randomised, 4-site trial will test the efficacy of a survivorship planning consultation (physicians receive CST and apply these skills in a new survivorship-focused office visit using a survivorship plan) with patients who have achieved complete remission after completion of first-line therapy versus a control arm in which physicians are trained to subsequently provide a time-controlled, manualised wellness rehabilitation consultation focused only on discussion of healthy nutrition and exercise as rehabilitation postchemotherapy. The primary outcome for physicians will be uptake and usage of communication skills and maintenance of these skills over time. The primary outcome for patients is changes in knowledge about lymphoma and adherence to physicians’ recommendations (eg, pneumococcus and influenza vaccinations); secondary outcomes will include perceptions of the doctor–patient relationship, decreased levels of cancer worry and depression, quality of life changes, satisfaction with care and usage of healthcare. This study will also examine the moderators and mediators of change within our theoretical model derived from Leventhal's Common-Sense Model of health beliefs. Ethics and dissemination This study was approved by the Institutional Review Boards at Memorial Sloan Kettering Cancer Centers and all other participating sites. This work is funded by the National Cancer Institute (R01 CA 151899 awarded to DWK and SH as coprincipal investigators). The

  3. Molecular cytogenetics: Rosetta Stone for understanding cancer - Twenty-ninth G. H. A. Clowes Memorial Award lecture

    SciTech Connect

    Rowley, J.D. )

    1990-07-01

    This article reviews the progress in the genetic changes that occur within the cancer that are critically involved in the transformation of a normal to a malignant cell. Clearly, to concentrate on genes to the exclusion of cell biology would be too narrow and short-sighted an approach. Nonetheless, the author is convinced that until the genes have isolated that are centrally involved in at least some of the malignant processes in different cell types, one will be unable to answer the fundamental questions about malignant transformation. More importantly, one will be unable to answer the questions with precision. The author limits consideration to those changes that have been detected by analyzing the karyotypic pattern of human cancer cells using chromosome banding, and in particular to those found in leukemia.

  4. Flashbulb Memories

    PubMed Central

    Hirst, William; Phelps, Elizabeth A.

    2015-01-01

    We review and analyze the key theories, debates, findings, and omissions of the existing literature on flashbulb memories (FBMs), including what factors affect their formation, retention, and degree of confidence. We argue that FBMs do not require special memory mechanisms and are best characterized as involving both forgetting and mnemonic distortions, despite a high level of confidence. Factual memories for FBM-inducing events generally follow a similar pattern. Although no necessary and sufficient factors straightforwardly account for FBM retention, media attention particularly shapes memory for the events themselves. FBMs are best characterized in term of repetitions, even of mnemonic distortions, whereas event memories evidence corrections. The bearing of this literature on social identity and traumatic memories is also discussed. PMID:26997762

  5. Skilled Memory.

    DTIC Science & Technology

    1980-11-06

    Morse code (Bryan & Harter , 1899). In every case, memory performance of the expert seems to violate the established limits of short- term memory. How is...of immediate memory. Quarterly Journal of Experimental psychology, 1958, 10, 12-21. Bryan, W. L., & Harter N. psychological Review, 1899, 6, 345-375...16, 1980 Page 5 Civil Govt Non Govt Dr. Susan Chipman 1 Dr. John R. Anderson Learning and Development Department of Psychology National Institute of

  6. Virtual memory

    NASA Technical Reports Server (NTRS)

    Denning, P. J.

    1986-01-01

    Virtual memory was conceived as a way to automate overlaying of program segments. Modern computers have very large main memories, but need automatic solutions to the relocation and protection problems. Virtual memory serves this need as well and is thus useful in computers of all sizes. The history of the idea is traced, showing how it has become a widespread, little noticed feature of computers today.

  7. CD45RO+ Memory T Lymphocytes — a Candidate Marker for TNM-Immunoscore in Squamous Non–Small Cell Lung Cancer1

    PubMed Central

    Paulsen, Erna-Elise; Kilvaer, Thomas; Khanehkenari, Mehrdad Rakaee; Maurseth, Ramona Johansen; Al-Saad, Samer; Hald, Sigurd M.; Al-Shibli, Khalid; Andersen, Sigve; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy; Donnem, Tom

    2015-01-01

    Tumor-infiltrating lymphocytes (TILs) are vital in limiting cancer progression and may supplement the TNM classification. CD45RO+ memory TILs show major prognostic impact in various malignancies but have not been extensively explored in non–small cell lung cancer (NSCLC). In this study, we aimed to evaluate their potential in a NSCLC TNM-Immunoscore. Tissue microarrays were constructed from tumor tissue samples from two cohorts including in total 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. The density of CD45RO+ and CD8+ TILs in tumor epithelial and stromal compartments of the tumors was evaluated by immunohistochemistry. In univariate analyses, intraepithelial CD45RO+ TIL density (T-CD45RO) was a significant prognostic factor for disease-specific survival (P = .007), limited to the squamous cell carcinoma (SCC) histology subgroup (P < .001), where it was significant in both cohorts (University Hospital of North Norway, P = .003; Nordland Hospital, P = .022). Combining T-CD45RO and stromal CD8+ TIL density (S-CD8) increased the prognostic impact in SCC (P < .001) and showed a significant impact within all pathological stages (I, P = .025; II, P < .001; III, P = .001). In the multivariate analysis, T-CD45RO was an independent positive prognostic factor for SCC (hazard ratio 2.65, 95% confidence interval 1.64-4.28, P < .001), and in combination with S-CD8, the prognostic impact increased vastly (high + high versus low + low: hazard ratio 6.50, 95% confidence interval 3.54-11.91, P < .001). In conclusion, T-CD45RO was an independent prognostic factor for SCC NSCLC. When combined with S-CD8, the prognostic impact increased and was significant within each pathological stage. We propose CD45RO as a candidate marker for TNM-Immunoscore in SCC NSCLC. PMID:26678911

  8. Comparison with published systems of a new staging system for papillary and follicular thyroid carcinoma.

    PubMed

    Wong, Ronnie Meiyi; Bresee, Catherine; Braunstein, Glenn D

    2013-05-01

    Several staging systems exist to estimate the prognosis for patients with thyroid carcinoma. Our goal was to develop a new staging system to predict cancer-specific survival (CSS) and evaluate it against published systems. The Cedars-Sinai Medical Center (CSMC)'s staging system was derived using data from an adjusted analysis of 1622 patients with differentiated thyroid carcinomas (DTCs) from the CSMC Thyroid Cancer Center. Mean follow-up time was 11.8 years. There were 1180 female and 442 male patients with a mean age of 46. Staging systems reviewed include University of Alabama (Birmingham) and M.D. Anderson Cancer Center (UAB-MDACC); the Tumor-Node-Metastasis (TNM) 5th and 7th editions; Memorial Sloan-Kettering (MSK); the National Thyroid Cancer Treatment Cooperative Study (NTCTCS); Ohio State; Clinical Class; Metastases, Age, Completeness of resection, Invasion, and tumor Size (MACIS); Noguchi; and the Yildirim model for predicting outcomes. The proportion of variance explained (PVE) and the C-index were computed to rank and compare each staging system's ability to predict CSS with this patient population. Adjusted hazard ratios revealed that age at surgery of >45 years, the presence of distant metastases, capsular invasion, and vascular invasion were the most significant predictors of CSS in this patient population. The final CSMC risk score consists of low-, moderate-, and high-risk groups. Among the well-differentiated thyroid carcinoma staging systems, the CSMC and NTCTCS ranked highest with PVE values of 5% and 4.3%, respectively, while the NTCTCS and CSMC staging systems were reversed using the C-index (0.77 and 0.76, respectively). The PVE and C-index values were relatively low across all applicable staging systems and varied in each study reviewed. This suggests that no one staging system has been shown to be superior to another across different patient populations with DTC. In the future, additional factors, such as biological markers, added to the

  9. Episodic Memories

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2009-01-01

    An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of "episodic elements," summary records of experience often in the form of visual images, associated to a "conceptual frame" that provides a…

  10. Collaging Memories

    ERIC Educational Resources Information Center

    Wallach, Michele

    2011-01-01

    Even middle school students can have memories of their childhoods, of an earlier time. The art of Romare Bearden and the writings of Paul Auster can be used to introduce ideas about time and memory to students and inspire works of their own. Bearden is an exceptional role model for young artists, not only because of his astounding art, but also…

  11. Memory Magic.

    ERIC Educational Resources Information Center

    Hartman, Thomas G.; Nowak, Norman

    This paper outlines several "tricks" that aid students in improving their memories. The distinctions between operational and figural thought processes are noted. Operational memory is described as something that allows adults to make generalizations about numbers and the rules by which they may be combined, thus leading to easier memorization.…

  12. Collaging Memories

    ERIC Educational Resources Information Center

    Wallach, Michele

    2011-01-01

    Even middle school students can have memories of their childhoods, of an earlier time. The art of Romare Bearden and the writings of Paul Auster can be used to introduce ideas about time and memory to students and inspire works of their own. Bearden is an exceptional role model for young artists, not only because of his astounding art, but also…

  13. Episodic Memories

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2009-01-01

    An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of "episodic elements," summary records of experience often in the form of visual images, associated to a "conceptual frame" that provides a…

  14. Memory conformity affects inaccurate memories more than accurate memories.

    PubMed

    Wright, Daniel B; Villalba, Daniella K

    2012-01-01

    After controlling for initial confidence, inaccurate memories were shown to be more easily distorted than accurate memories. In two experiments groups of participants viewed 50 stimuli and were then presented with these stimuli plus 50 fillers. During this test phase participants reported their confidence that each stimulus was originally shown. This was followed by computer-generated responses from a bogus participant. After being exposed to this response participants again rated the confidence of their memory. The computer-generated responses systematically distorted participants' responses. Memory distortion depended on initial memory confidence, with uncertain memories being more malleable than confident memories. This effect was moderated by whether the participant's memory was initially accurate or inaccurate. Inaccurate memories were more malleable than accurate memories. The data were consistent with a model describing two types of memory (i.e., recollective and non-recollective memories), which differ in how susceptible these memories are to memory distortion.

  15. Chromosomal Mapping by Means of Mutational Induction in Synchronous Populations of Streptococcus faecalis

    PubMed Central

    Stonehill, E. H.; Hutchison, Dorris J.

    1966-01-01

    Stonehill, E. H. (Sloan-Kettering Institute for Cancer Research, New York, N.Y. and Dorris J. Hutchison. Chromosomal mapping by means of mutational induction in synchronous populations of Streptococcus faecalis. J. Bacteriol. 92:136–143. 1966.—A new method for mapping genetic loci on the bacterial chromosome, based on the linear progression of the deoxyribonucleic acid-replicating enzyme (replicase) in synchronous cultures of Streptococcus faecalis, is described. Ultraviolet irradiation was used to induce mutations to drug and to bacteriophage resistance at various intervals during the progress of the replicase along the chromosome. The time of duplication of the gene in synchronous populations was determined from reductions in the rates of irradiation-induced mutation. After the replication of various genes, the rates fell to half their former values. The resulting data made possible the construction of a 1-hr time-map indicating the sequence of replication of five genes in S. faecalis. PMID:4957554

  16. World gynecologic oncology publications and the Turkish contribution to the literature between 2000 and 2007.

    PubMed

    Dursun, Polat; Gultekin, Murat; Ayhan, Ali

    2011-01-01

    To investigate the number of publications and the contribution from top-ranking countries, institutions, and authors in 3 gynecologic oncology journals (Gynecologic Oncology [GO], International Journal of Gynecological Cancer [IJGC], and European Journal of Gynaecological Oncology [EJGO]),as well as the degree of Turkish contribution between 2000 and 2007. Articles published between 2000 and 2007 in 3 gynecologic oncology journals indexed by the Science Citation Index were accessed via the ISI-Thomson website. Additionally, PubMed, Sciencedirect, and Blackwell-Synergy databases were used to identify the originating countries and institutions of the published articles. The types of articles, originating countries, and names of the institutions and authors were determined. Furthermore, the number of articles affiliated with Turkish institutions and the publication year were also determined. We located 6,851 articles published in the 3 journals. During this period 36.1%, 7.7%, 7.2%, 5.8% and 4.8% of the papers originated from the USA, Japan, Italy, Turkey, and England, respectively. The 5 most productive institutions were the University of Texas, Memorial Sloan-Kettering Cancer Center, Roswell Park Cancer Institute, University of Alabama, and University of Athens. The 5 most productive authors were Markman (USA), Chi (USA), Ayhan (Turkey), Barakat (USA), and Vergote (Belgium), respectively. In all, 36.1% of the papers originated from the USA, while 44% originated from 17 European countries. The USA was the first-ranked country of origin in GO and IJGC, while Turkey was the first-ranked country of origin in EJGO. Overall, 399 (5.8%) papers originated from Turkish institutions. Most of the gynecologic oncology publications originated from the USA and Western European countries, where gynecologic oncology training is available and surgical and research traditions are well established. On the other hand, Turkish researchers made an important contribution to gynecologic

  17. GMK (Progenics Pharmaceuticals).

    PubMed

    Knutson, Keith L

    2002-01-01

    Progenics Pharmaceuticals is developing GMK vaccine (a ganglioside conjugate vaccine coupled to keyhole limpet hemocyanin and formulated with the adjuvant QS-21), licensed from the Memorial Sloan-Kettering Cancer Center, for the potential treatment of melanoma and other cancers [194258], [325284]. It was previously under co-development with Bristol-Myers Squibb, but in May 2001, all rights to the GMK vaccine were returned to Progenics [409168]. It was the first of a new class of ganglioside conjugate vaccine evaluated by Progenics [194258]. GMK vaccination induces antibodies against GM2 ganglioside capable of specifically killing melanoma cells. Melanoma patients with antibodies against GM2 ganglioside have significantly improved disease-free and overall survival compared to antibody-negative subjects. The vaccine is undergoing two phase III trials, the first comparing GMK to high-dose IFNalpha in melanoma patients with more serious disease and at a high risk of relapse, and the second, in collaboration with the European Organization for Research and Treatment of Cancer, comparing GMK (14 doses of GMK over three years) to no treatment other than close monitoring of malignant melanoma patients at immediate risk of relapse [409168]. In February 1999, Lehman Brothers predicted that the vaccine had a 50% probability of reaching market, with an estimated first launch date in 2002. The analysts predicted potential peak sales in 2008 of $150 million in the US and $100 million in the rest of the world at that time [319225]. In January 2000, Lehman Brothers expected that an NDA filing would take place in 2002, with possible launch of the vaccine in 2003. In addition, Lehman Brothers estimated potential peak sales at $500 million [357788]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of GMK and PRO-542 in 2002 [390063]. In July 2001, Ladenburg Thalmann predicted a $257 million

  18. Memory after treatment for acute lymphoblastic leukaemia.

    PubMed Central

    Rodgers, J; Britton, P G; Morris, R G; Kernahan, J; Craft, A W

    1992-01-01

    Long term survivors of acute lymphoblastic leukaemia (ALL) often experience cognitive difficulties, which may be related to impairment of memory function. Memory ability has been studied in a group of survivors of ALL along with sibling controls and in children who have received treatment for other forms of cancer. Children in the ALL group were found to have significant deficits in memory function in tasks which required the application of strategic planning behaviour. These deficits are potentially remediable by educational strategies. PMID:1575545

  19. Phenomenology of the subtypes of delirium: phenomenological differences between hyperactive and hypoactive delirium.

    PubMed

    Boettger, Soenke; Breitbart, William

    2011-06-01

    The purpose of this study was to examine the differences in phenomenology between hypoactive and hyperactive subtypes of delirium, and specifically to determine the comparative prevalence of perceptual disturbances (e.g., hallucinations) and delusions in these two subtypes of delirium. We conducted an analysis of Memorial Delirium Assessment Scale (MDAS) items in a set of 100 delirium cases evaluated and treated at Memorial Sloan-Kettering Cancer Center (MSKCC) utilizing an MSKCC Institutional Review Board (IRB) approved Clinical Delirium Database. Individual MDAS items, reflecting the phenomenology of delirium, were compared in delirious patients classified as to motoric subtype (hypoactive versus hyperactive based on MDAS item no. 9, psychomotor activity). Particular attention was paid to differences between subtypes as to the prevalence of perceptual disturbances (MDAS item no. 7) and delusions (MDAS item no. 8). Significant differences were found between hyperactive and hypoactive subtypes of delirium for the presence and severity of perceptual disturbances and delusions; with perceptual disturbances (e.g., hallucinations) and delusions being significantly more prevalent in hyperactive than in hypoactive delirium. The prevalence of perceptual disturbances was 50.9% and the prevalence of delusions was 43.4% in patients with hypoactive delirium. In patients with hyperactive delirium, the prevalence of perceptual disturbances was 70.2% and the prevalence of delusions was 78.7%. The prevalence of perceptual disturbances and delusions in both subtypes of delirium was significantly correlated with the presence of moderate-to-severe disturbance of consciousness/arousal (MDAS item no. 1) and attention impairment (MDAS item no. 5), but was not correlated with the presence of moderate-to-severe cognitive impairment (MDAS item nos. 2-4). Contrary to earlier studies, which indicated extremely low prevalence rates of perceptual disturbances (e.g., hallucinations) and

  20. Memory loss

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003257.htm Memory loss To use the sharing features on this ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  1. Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications

    PubMed Central

    Hicks, Angel Mier; Chou, Joanne; Capanu, Marinela; Lowery, Maeve A.; Yu, Kenneth H.; O’Reilly, Eileen M.

    2016-01-01

    This was a cohort analysis evaluating patients with pancreatic adenocarcinoma who presented with or developed ascites. Among the 180 patients analyzed, the use of serial paracenteses and indwelling catheters is a common practice to effect symptom palliation. The complication rate was higher in patients with indwelling catheters. Analyzing ascitic fluid and calculating the serum ascites albumin gradient can help attribute the etiology of the ascites and potentially identify which patients may benefit from diuretics or other intervention. Background Ascites develops in a subset of patients with pancreatic adenocarcinoma (PAC) at presentation or as the disease advances. Limited data exist on the prognostic importance of malignant ascites in PAC. Our hypothesis is that this information will provide an understanding of the natural history and facilitate management decisions. Methods We conducted a retrospective analysis of 180 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between January 1, 2009 and December 31, 2014, with PAC and with ascites either at presentation or that developed during the disease course. Results For the 180 patients, the overall survival was 15 months. The time from diagnosis to ascites presentation was 11 months, and the survival time after ascites development was 1.8 months (range, 1.6–2.3 months; 95% confidence interval). Of 62 patients (34%) who had ascitic fluid analyzed, 36 (58%) had positive cytology. Fifty-one (82%) patients had a serum ascites albumin gradient ≥ 1, and 11 (18%) had serum ascites albumin gradient < 1. Sixty-four (36%) patients had their ascites managed solely by serial paracenteses. A total of 116 patients required a catheter; of these, 108 (93%) had a Tenckhoff catheter, 4 (3%) a Pleurx catheter, 4 (3%) a pigtail catheter, and 1 (1%) a Denver catheter. Eight (7%) patients required 2 catheters to be placed, and in 6 (5%), Tenckhoff catheters had to be removed. The main observed complications were

  2. Activation-induced cell death of memory CD8+ T cells from pleural effusion of lung cancer patients is mediated by the type II Fas-induced apoptotic pathway.

    PubMed

    Prado-Garcia, Heriberto; Romero-Garcia, Susana; Morales-Fuentes, Jorge; Aguilar-Cazares, Dolores; Lopez-Gonzalez, Jose Sullivan

    2012-07-01

    Lung cancer is the second most common form of cancer and the leading cause of cancer death worldwide. Pleural effusions, containing high numbers of mononuclear and tumor cells, are frequent in patients with advanced stages of lung cancer. We reported that in pleural effusions from primary lung cancer, the CD8+ T cell subpopulation, and particularly the terminally differentiated subset, is reduced compared to that of non-malignant effusions. We analyzed the participation of activation-induced cell death (AICD) and extrinsic pathways (type I or II) as mechanisms for the decrease in pleural effusion CD8+ T cell subpopulation. Pleural effusion or peripheral blood CD4+ and CD8+ T cells, from lung cancer patients, were stimulated with anti-CD3 antibody and analyzed for (a) apoptosis by annexin-V-binding and TUNEL assay, (b) transcript levels of Fas ligand (FasL) and TRAIL by real-time RT-PCR, (c) expression of FasL and TRAIL, measured as integrated mean fluorescence intensities (iMFI) by flow cytometry, (d) expression of Bcl-2 and BIM molecules, measured as MFI, and (e) apoptosis inhibition using caspase-8 and -9 inhibitors. Pleural effusion CD8+ T cells, but not CD4+ T cells, from cancer patients underwent AICD. Blocking FasL/Fas pathway protected from AICD. Upregulation of FasL and TRAIL expressions was found in pleural effusion CD8+ T cells, which also showed a subset of Bcl-2 low cells. In memory CD8+ T cells, AICD depended on both extrinsic and intrinsic apoptotic pathways. Hence, in the pleural space of lung cancer patients, AICD might compromise the antitumor function of CD8+ T cells.

  3. Memory consolidation.

    PubMed

    Squire, Larry R; Genzel, Lisa; Wixted, John T; Morris, Richard G

    2015-08-03

    Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., "neural replay," which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  4. Memory Consolidation

    PubMed Central

    Squire, Larry R.; Genzel, Lisa; Wixted, John T.; Morris, Richard G.

    2015-01-01

    Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., “neural replay,” which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation. PMID:26238360

  5. Fear Memory.

    PubMed

    Izquierdo, Ivan; Furini, Cristiane R G; Myskiw, Jociane C

    2016-04-01

    Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

  6. Is external memory memory? Biological memory and extended mind.

    PubMed

    Michaelian, Kourken

    2012-09-01

    Clark and Chalmers (1998) claim that an external resource satisfying the following criteria counts as a memory: (1) the agent has constant access to the resource; (2) the information in the resource is directly available; (3) retrieved information is automatically endorsed; (4) information is stored as a consequence of past endorsement. Research on forgetting and metamemory shows that most of these criteria are not satisfied by biological memory, so they are inadequate. More psychologically realistic criteria generate a similar classification of standard putative external memories, but the criteria still do not capture the function of memory. An adequate account of memory function, compatible with its evolution and its roles in prospection and imagination, suggests that external memory performs a function not performed by biological memory systems. External memory is thus not memory. This has implications for: extended mind theorizing, ecological validity of memory research, the causal theory of memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Cancer

    MedlinePlus

    ... Healthcare ManagementFamily HealthProcedures & DevicesHealthcare ManagementRelated TopicsCancer: Medical VocabularyRead Article >>Cancer: Medical Vocabulary Learn the definitions of various terms ...

  8. Cancer

    MedlinePlus

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  9. Working memory.

    PubMed

    Baddeley, A

    1992-01-31

    The term working memory refers to a brain system that provides temporary storage and manipulation of the information necessary for such complex cognitive tasks as language comprehension, learning, and reasoning. This definition has evolved from the concept of a unitary short-term memory system. Working memory has been found to require the simultaneous storage and processing of information. It can be divided into the following three subcomponents: (i) the central executive, which is assumed to be an attentional-controlling system, is important in skills such as chess playing and is particularly susceptible to the effects of Alzheimer's disease; and two slave systems, namely (ii) the visuospatial sketch pad, which manipulates visual images and (iii) the phonological loop, which stores and rehearses speech-based information and is necessary for the acquisition of both native and second-language vocabulary.

  10. Allogeneic Hematopoietic Stem Cell Transplantation is Underutilized in Older Patients with Myelodysplastic Syndromes.

    PubMed

    Getta, Bartlomiej M; Kishtagari, Ashwin; Hilden, Patrick; Tallman, Martin S; Maloy, Molly; Gonzales, Patrick; Castro-Malaspina, Hugo; Perales, Miguel-Angel; Giralt, Sergio; Tamari, Roni; Klimek, Virginia

    2017-03-20

    Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The proportion of MDS patients referred for transplant evaluation, those undergoing transplantation and the reasons for not undergoing transplant are unknown. In this retrospective analysis, pre-defined HCT eligibility and indications criteria were applied to 362 unselected patients with newly diagnosed MDS seen by Leukemia faculty between 2008 and 2015 at Memorial Sloan Kettering Cancer Center. Two hundred ninety four patients (81%) were deemed eligible for transplant and among these, transplant was considered indicated in 244 (83%). Of these, 158/244 (65%) were referred for transplant evaluation at a median of 3.9 months from diagnosis. Overall 120/362 (33%) underwent transplant at a median of 7.7 months from diagnosis. Metastatic solid organ malignancy was the major reason for transplant ineligibility (54%), and death due to MDS, which occurred in 41% of candidates who were not transplanted, was the major reason for not undergoing transplant. Factors associated with a lower likelihood of referral for transplant evaluation included age ≥65 (p<0.001), ≥2 co-morbidities (p=0.008), intermediate-1/low risk MDS (p<0.001), <5% blasts at diagnosis (overall p<0.001), having medicare/medicaid health insurance (p<0.001), not being married (p=0.017) and diagnosis between 2008-2011 (p=0.035). On multivariate analysis adjusting for all of the previous, diagnosis between 2008-2011 (p<0.001), age ≥65 (p=0.001) and <5% blasts at diagnosis (overall p=0.031) were associated with a lower likelihood of referral for transplant evaluation. Factors associated with a lower likelihood of undergoing transplant included age ≥65 (p<0.001), ≥2 co-morbidities (p=0.003), intermediate-1/low risk MDS (p<0.001), <5% blasts (overall p<0.001), very low/low/intermediate risk IPSS-R karyotype (p=0.018) and having medicare/medicaid health insurance (p<0.001). In

  11. The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

    PubMed Central

    Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young

    2015-01-01

    Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value

  12. Invasion patterns in stage I endometrioid and mucinous ovarian carcinomas: a clinicopathologic analysis emphasizing favorable outcomes in carcinomas without destructive stromal invasion and the occasional malignant course of carcinomas with limited destructive stromal invasion.

    PubMed

    Chen, Shirley; Leitao, Mario M; Tornos, Carmen; Soslow, Robert A

    2005-07-01

    Stage I, low-grade endometrioid and mucinous ovarian carcinomas have an excellent prognosis. Published data have suggested that destructive stromal invasion, a relatively uncommon finding in these tumors, is a poor prognostic factor. We investigated this by studying all FIGO stage I, grades 1 and 2 (of 3) endometrioid and mucinous ovarian carcinomas that were surgically staged at the Memorial Sloan-Kettering Cancer Center from 1980 to 2000. We undertook a careful review of all available slides using current diagnostic criteria and correlated histopathologic indices with clinical outcome data. Cases studied included 13 endometrioid ovarian carcinomas (stage IA, eight; stage IC, five) and six intestinal mucinous ovarian carcinomas (stage IA, three; stage IC, three). All of the tumors contained areas of expansile invasion, greater than that acceptable for microinvasion, and were thus diagnosed as carcinomas instead of borderline tumors. Nevertheless, nearly all demonstrated borderline tumor (noninvasive) components. Six tumors contained at least one focus of destructive stromal invasion (two endometrioid and four mucinous ovarian carcinomas). Four additional cases showed a focus suspicious for but not diagnostic of destructive invasion ('indeterminate for destructive invasion') (two endometrioid and two mucinous ovarian carcinomas). Follow-up data were available for 17 patients. The median follow-up was 81 months (range, 9-161 months). In all, 14 patients were alive with no evidence of disease (expansile invasion alone, eight; destructive stromal invasion, four; and indeterminate for destructive invasion, two). Three patients died of their disease (destructive stromal invasion, two; and indeterminate for destructive invasion, one). The size, number, and nuclear grade of destructive stromal invasion foci did not appear to have an impact on survival in this relatively limited number of patients. Outcome data in patients with stage I, low-grade endometrioid and mucinous

  13. Algorithms in the First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma--Analysis Using Diagnostic Nodes.

    PubMed

    Rothermundt, Christian; Bailey, Alexandra; Cerbone, Linda; Eisen, Tim; Escudier, Bernard; Gillessen, Silke; Grünwald, Viktor; Larkin, James; McDermott, David; Oldenburg, Jan; Porta, Camillo; Rini, Brian; Schmidinger, Manuela; Sternberg, Cora; Putora, Paul M

    2015-09-01

    With the advent of targeted therapies, many treatment options in the first-line setting of metastatic clear cell renal cell carcinoma (mccRCC) have emerged. Guidelines and randomized trial reports usually do not elucidate the decision criteria for the different treatment options. In order to extract the decision criteria for the optimal therapy for patients, we performed an analysis of treatment algorithms from experts in the field. Treatment algorithms for the treatment of mccRCC from experts of 11 institutions were obtained, and decision trees were deduced. Treatment options were identified and a list of unified decision criteria determined. The final decision trees were analyzed with a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees. The most common treatment recommendations were determined, and areas of discordance were identified. The analysis revealed heterogeneity in most clinical scenarios. The recommendations selected for first-line treatment of mccRCC included sunitinib, pazopanib, temsirolimus, interferon-α combined with bevacizumab, high-dose interleukin-2, sorafenib, axitinib, everolimus, and best supportive care. The criteria relevant for treatment decisions were performance status, Memorial Sloan Kettering Cancer Center risk group, only or mainly lung metastases, cardiac insufficiency, hepatic insufficiency, age, and "zugzwang" (composite of multiple, related criteria). In the present study, we used diagnostic nodes to compare treatment algorithms in the first-line treatment of mccRCC. The results illustrate the heterogeneity of the decision criteria and treatment strategies for mccRCC and how available data are interpreted and implemented differently among experts. The data provided in the present report should not be considered to serve as treatment recommendations for the management of treatment-naïve patients with multiple metastases from metastatic clear cell renal cell carcinoma outside

  14. CD34-selected hematopoietic stem cell transplants conditioned with myeloablative regimens and anti-thymocyte globulin for advanced myelodysplastic syndrome: limited graft-versus-host disease without increased relapse

    PubMed Central

    Tamari, Roni; Chung, Steven; Papadopoulos, Esperanza B.; Jakubowski, Ann A.; Hilden, Patrick; Devlin, Sean M.; Goldberg, Jenna D.; Perales, Miguel-Angel; Ponce, Doris M.; Sauter, Craig S.; Maloy, Molly A.; Herman, Dara Y; Klimek, Virginia; Young, James W.; O'Reilly, Richard J.; Giralt, Sergio A.; Castro-Malaspina, Hugo

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for patients with myelodysplastic syndrome (MDS). Donor T cells are critical for graft-versus-tumor effect (GVT) but carry the risk of graft-versus-host disease (GVHD). CD34 selection with immunomagnetic beads has been an effective method of depleting alloreactive donor T cells from the peripheral blood graft and has been shown to result in significant reduction in acute and chronic GVHD. We analyzed the outcomes of 102 adults (median age 57.6 years) with advanced MDS who received a CD34 selected allo-HSCT between January 1997 and April 2012 at Memorial Sloan Kettering Cancer Center. The cumulative incidence (CI) of grade II-IV acute GVHD at day 100 was 9.8% (95% CI: 5.0-16.5%) and at day 180, 15.7% (95% CI: 9.4-23.4%). The CI of chronic GVHD at 1 year was 3.9% (95% CI: 1.3-9.0%). The CI of relapse at 1 year was 11.8% (95% CI: 6.4-18.9%) and at 2 years 15.7% (95% CI: 9.4-23.4%). Forty-eight patients were alive with a median follow-up of 71.7 months. The overall survival (OS) at 2 years was 56.9% (95% CI: 48-67.3%) and at 5 years, 49.3% (95% CI: 40.4-60.2%). Relapse-free survival (RFS) at 2 years was 52.0% (95% CI: 41.9-61.1%) and at 5 years, 47.6% (95% CI: 37.5-56.9%). The CI of non-relapse mortality was 7.8% (95% CI: 3.7-14.1%) at day 100, 22.5% (95% CI 15.0-31.1%) at 1 year and 33.4% (95% CI:24.2-42.6%) at 5 years post-transplant. Chronic GVHD/relapse-free survival (CRFS) overlapped with RFS. These findings demonstrate that ex-vivo T- cell depleted (TCD) allo-HSCT by CD34 selection offers long term OS and RFS with low incidences of acute and chronic GVHD and without an increased risk of relapse. PMID:26187863

  15. Intraductal tubular neoplasms of the bile ducts.

    PubMed

    Katabi, Nora; Torres, Javiera; Klimstra, David S

    2012-11-01

    Although most tumors of the bile ducts are predominantly invasive, some have an exophytic pattern within the bile ducts; these intraductal papillary neoplasms usually have well-formed papillae at the microscopic level. In this study, however, we describe a novel type of intraductal neoplasm of the bile ducts with a predominantly tubular growth pattern and other distinctive features. Ten cases of biliary intraductal neoplasms with a predominantly tubular architecture were identified in the files of the Pathology Department at Memorial Sloan-Kettering Cancer Center from 1983 to 2006. For each of these cases we studied the clinical presentation, histologic and immunohistochemical features (9 cases only), and the clinical follow-up of the patients. Three male and 7 female patients (38 to 78 y) presented with obstructive jaundice or abdominal pain. Eight of the patients underwent a partial hepatectomy; 2 underwent a laparoscopic bile duct excision, followed by a pancreatoduodenectomy in one of them. The tumors range in size from 0.6 to 8.0 cm. The intraductal portions of the tumors (8 intrahepatic, 1 extrahepatic hilar, 1 common bile duct) were densely cellular and composed of back-to-back tubular glands and solid sheets with minimal papillary architecture. The cells were cuboidal to columnar with mild to moderate cytologic atypia. Foci of necrosis were present in the intraductal component in 6 cases. An extraductal invasive carcinoma component was present in 7 cases, composing <25% of the tumor in 4 cases, and >75% in 1 case. It was observed by immunohistochemical analysis that the tumor cells expressed CK19, CA19-9, MUC1, and MUC6 in most cases and that SMAD4 expression was retained. MUC2, MUC5AC, HepPar1, synaptophysin, chromogranin, p53, and CA125 were negative in all cases and most were negative for CEA-M and B72.3. Four patients were free of tumor recurrence after 7 to 85 months (average, 27 mo). Four patients with an invasive carcinoma component suffered

  16. Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    SciTech Connect

    Rosenzweig, Kenneth E.; Zauderer, Marjorie G.; Laser, Benjamin; Krug, Lee M.; Yorke, Ellen; Sima, Camelia S.; Flores, Raja; Rusch, Valerie

    2012-07-15

    Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach. Methods and Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering Cancer Center. Results: Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months. Conclusions: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy

  17. Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.

    PubMed

    Dickson, Mark A; Schwartz, Gary K; Keohan, Mary Louise; D'Angelo, Sandra P; Gounder, Mrinal M; Chi, Ping; Antonescu, Cristina R; Landa, Jonathan; Qin, Li-Xuan; Crago, Aimee M; Singer, Samuel; Koff, Andrew; Tap, William D

    2016-07-01

    More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and xenografts. Our prior phase 2 study demonstrated that treatment with palbociclib (200 mg daily for 14 days every 21 days) resulted in clinical benefit in WD/DDLS but moderate hematologic toxic effects. It is important to understand whether palbociclib at a new dose and schedule-125 mg daily for 21 days every 28 days-results in clinical benefit and manageable toxic effects. To determine the progression-free survival (PFS) at 12 weeks of patients with WD/DDLS treated with palbociclib (PD0332991). In this phase 2, nonrandomized, open-label clinical trial conducted at the Memorial Sloan Kettering Cancer Center, 60 patients 18 years and older with advanced WD/DDLS and measurable disease by RECIST 1.1 were enrolled from December 2011 to January 2014 and followed to March 2015. Patients received oral palbociclib at 125 mg daily for 21 days in 28-day cycles. Primary end point was PFS. Secondary end points included response rate and toxic effects. Overall, 30 patients were enrolled in the initial cohort and 30 more in an expansion cohort. Median (range) age was 61.5 (35-87) years; 31 patients (52%) were male; median (range) Eastern Cooperative Oncology Group score was 0 (0-1). Progression-free survival at 12 weeks was 57.2% (2-sided 95% CI, 42.4%-68.8%), and the median PFS was 17.9 weeks (2-sided 95% CI, 11.9-24.0 weeks). There was 1 complete response. Toxic effects were primarily hematologic and included neutropenia (grade 3, n = 20 [33%]; grade 4, n = 2 [3%]) but no neutropenic fever. In patients with advanced WD/DDLS, treatment with palbociclib was associated with a favorable PFS and occasional tumor response. This dose and schedule appears active and may have less toxic effects than 200 mg for 14 days. clinicaltrials.gov Identifier: NCT

  18. The core competencies of James Marion Sims, MD.

    PubMed

    Straughn, J Michael; Gandy, Roy E; Rodning, Charles B

    2012-07-01

    The concept of core competencies in graduate medical education was introduced by the Accreditation Council for Graduate Medical Education of the American Medical Association to semiquantitatively assess the professional performance of students, residents, practitioners, and faculty. Many aspects of the career of J. Marion Sims, MD, are exemplary of those core competencies: MEDICAL KNOWLEDGE: Author of the first American textbook related to gynecology. MEDICAL CARE: Innovator of the Sims' Vaginal Speculum, Sims' Position, Sims' Test, and vesico-/rectovaginal fistulorrhaphy; advocated abdominal exploration for penetrating wounds; performed the first cholecystostomy. PROFESSIONALISM: Served as President of the New York Academy of Medicine, the American Medical Association, and the American Gynecologic Society. INTERPERSONAL RELATIONSHIPS/COMMUNICATION: Cared for the indigent, hearthless, indentured, disenfranchised; served as consulting surgeon to the Empress Eugénie (France), the Duchess of Hamilton (Scotland), the Empress of Austria, and other royalty of the aristocratic Houses of Europe; accorded the National Order of the Legion of Honor. PRACTICE-BASED LEARNING: Introduction of silver wire sutures; adoption of the principles of asepsis/antisepsis; adoption of the principles of general anesthesia. SYSTEMS-BASED PRACTICE: Established the Woman's Hospital, New York City, New York, the predecessor of the Memorial Sloan-Kettering Center for the Treatment of Cancer and Allied Diseases; organized the Anglo-American Ambulance Corps under the patronage of Napoleon III. What led him to a life of clinical and humanitarian service? First, he was determined to succeed. His formal medical/surgical education was perhaps the best available to North Americans during that era. Second, he was courageous in experimentation and innovation, applying new developments in operative technique, asepsis/antisepsis, and general anesthesia. Third, his curiosity was not burdened by rigid

  19. The Role of Color and Morphologic Characteristics in Dermoscopic Diagnosis.

    PubMed

    Bajaj, Shirin; Marchetti, Michael A; Navarrete-Dechent, Cristian; Dusza, Stephen W; Kose, Kivanc; Marghoob, Ashfaq A

    2016-06-01

    Both colors and structures are considered important in the dermoscopic evaluation of skin lesions but their relative significance is unknown. To determine if diagnostic accuracy for common skin lesions differs between gray-scale and color dermoscopic images. A convenience sample of 40 skin lesions (8 nevi, 8 seborrheic keratoses, 7 basal cell carcinomas, 7 melanomas, 4 hemangiomas, 4 dermatofibromas, 2 squamous cell carcinomas [SCCs]) was selected and shown to attendees of a dermoscopy course (2014 Memorial Sloan Kettering Cancer Center dermoscopy course). Twenty lesions were shown only once, either in gray-scale (n = 10) or color (n = 10) (nonpaired). Twenty lesions were shown twice, once in gray-scale (n = 20) and once in color (n = 20) (paired). Participants provided their diagnosis and confidence level for each of the 60 images. Of the 261 attendees, 158 participated (60.5%) in the study. Most were attending physicians (n = 76 [48.1%]). Most participants were practicing or training in dermatology (n = 144 [91.1%]). The median (interquartile range) experience evaluating skin lesions and using dermoscopy of participants was 6 (13.5) and 2 (4.0) years, respectively. Diagnostic accuracy and confidence level of participants evaluating gray-scale and color images. Two separate analyses were performed: (1) an unpaired evaluation comparing gray-scale and color images shown either once or for the first time, and (2) a paired evaluation comparing pairs of gray-scale and color images of the same lesion. In univariate analysis of unpaired images, color images were less likely to be diagnosed correctly compared with gray-scale images (odds ratio [OR], 0.8; P < .001). Using gray-scale images as the reference, multivariate analyses of both unpaired and paired images found no association between correct lesion diagnosis and use of color images (OR, 1.0; P = .99, and OR, 1.2; P = .82, respectively). Stratified analysis of paired images using

  20. Growth-Curve Modeling of Nevi With a Peripheral Globular Pattern

    PubMed Central

    Bajaj, Shirin; Dusza, Stephen W.; Marchetti, Michael A.; Wu, Xinyuan; Fonseca, Maira; Kose, Kivanc; Brito, Johanna; Carrera, Cristina; Martins de Silva, Vanessa P.; Malvehy, Josep; Puig, Susana; Yagerman, Sarah; Liebman, Tracey N.; Scope, Alon; Halpern, Allan C.; Marghoob, Ashfaq A.

    2017-01-01

    IMPORTANCE Although nevi with a peripheral rim of globules (peripheral globular nevi [PGN]) observed with dermoscopy are associated with enlarging melanocytic nevi, their actual growth dynamics remain unknown. Because change is a sensitive but nonspecific marker for melanoma, beginning to understand the growth patterns of nevi may improve the ability of physicians to differentiate normal from abnormal growth and reduce unnecessary biopsies. OBJECTIVE To study the growth dynamics and morphologic evolution of PGN on dermoscopy. DESIGN, SETTING, AND PARTICIPANTS A total of 84 participants with 121 PGN from September 1, 1999, through May 1, 2013, were identified retrospectively. Cohorts were recruited from the Memorial Sloan Kettering Cancer Center; Melanoma Unit of the Hospital Clinic, University of Barcelona; and Study of Nevi in Children. All 3 cohorts underwent longitudinal monitoring with serial dermoscopic imaging of their PGN. Data analysis was performed from May 1, 2014, through April 1, 2015. MAIN OUTCOMES AND MEASURES Establishment of the natural growth curve of PGN. The secondary aim was to establish the median time to growth cessation in those PGN for which the size eventually stabilized and/or had begun to decrease during the study period. RESULTS The median duration of follow-up was 25.1 (range, 2.0–114.4) months. Most of the nevi (116 [95.9%]) enlarged at some point during sequential monitoring. The rate of increase in the surface area of PGN varied among cohorts and ranged from −0.47 to 2.26mm2/mo (mean rate, 0.25 [95% CI, 0.14–0.36]mm2/mo). The median time to growth cessation in the 26 PGN that stabilized or decreased in size (21.5%) was 58.6 months. All lesions changed in a symmetric manner and 91 (75.2%) displayed a decrease in the density of peripheral globules over time. CONCLUSIONS AND RELEVANCE Nevi displaying a peripheral globular pattern enlarged symmetrically with apparent growth cessation occurring during a span of 4 to 5 years. Our

  1. Patterns of Failure for Rhabdomyosarcoma of the Perineal and Perianal Region

    SciTech Connect

    Casey, Dana L.; Wexler, Leonard H.; LaQuaglia, Michael P.; Meyers, Paul A.; Wolden, Suzanne L.

    2014-05-01

    Purpose: To analyze prognostic factors and patterns of failure for rhabdomyosarcoma of the perineal and perianal region (PRMS), with an emphasis on radiation therapy for locoregional control. Methods and Materials: Detailed records of all 14 patients treated for PRMS at Memorial Sloan-Kettering Cancer Center between 1998 and 2012 were reviewed. The Kaplan-Meier method was used to assess the event-free survival (EFS) and overall survival (OS), and a competing-risks analysis was used to assess the cumulative incidence of local, regional, and distant failures. Results: Median age was 15.8 years (range, 1.1-31.9 years). High-risk features were identified: 9 of 14 patients (64%) had group 3 disease and 3 of 14 (21%) had group 4; 11 of 14 tumors (78%) were alveolar; 12 of 14 tumors (86%) were ≥5 cm; and 9 of 14 patients (64%) had involved lymph nodes (N1). Of those aged ≥10 years at diagnosis, 9 of 10 (90%) had alveolar histology, all had tumors ≥5 cm, and 8 of 10 (80%) presented with N1 disease. The rates of local, regional, and distant failure at 5 years were 17%, 31%, and 52%, respectively. Although 3 of the 4 patients with regional failure received nodal irradiation, only one of the nodal failures occurred in the radiation therapy field. The 5-year EFS was 33%, and OS was 39%. Age ≥10 years was associated with poor outcomes: EFS was 13% in patients aged ≥10 years, compared with 75% in those aged <10 years (P=.04); the OS was 13% in patients aged ≥10 years, compared with 100% in those aged <10 years (P=.04). Conclusions: Patients with PRMS, especially those aged ≥10 years, present with poor prognostic features and continue to have poor outcomes. Given the high incidence of regional node recurrence, we recommend prophylactic ilioinguinal lymph node irradiation for all patients aged ≥10 years. For children aged <10 years, nodal evaluation is essential to determine the role for lymph node irradiation.

  2. Low-Stage High-Grade Serous Ovarian Carcinomas: Support for an Extraovarian Origin.

    PubMed

    Morency, Elizabeth; Leitao, Mario M; Soslow, Robert A

    2016-05-01

    Many adnexal high-grade serous carcinomas (HGSCs) may derive from microscopic precursors in the fallopian tube. By studying a series of low-stage ovarian carcinomas, we anticipated that HGSCs would be distributed in a pattern suggesting secondary involvement, helping to indirectly validate the fallopian tube origin theory, and that most ovarian carcinomas other than serous carcinomas would demonstrate features consistent with derivation from precursors located in or transplanted to the ovary. Seventy-six patients with low-stage (FIGO I/II) sporadic ovarian carcinoma who underwent primary surgical management at Memorial Sloan Kettering Cancer Center from 1980 to 2000 were included in the study. Histologic type was assigned using Gilks' criteria. Similar to the approach taken when distinguishing primary and metastatic mucinous or endometrioid carcinoma involving ovary, cases interpreted as showing a "primary" pattern of ovarian involvement had ≥3 of the following features: unilateral tumor, size >12 cm, no surface involvement, no multinodularity, and no destructive stromal invasion. All other cases were considered to show a "metastatic" pattern of ovarian involvement. Cases were evaluated for p53 and WT-1 expression, using standard techniques on a tissue microarray. TP53 gene sequencing was also performed. Cases comprised HGSC (n=22), endometrioid carcinoma (n=30), clear cell carcinoma (n=13), and mucinous carcinoma (n=11). HGSCs displayed substantially more "metastatic features" than the non-HGSC group and a mean overall size that was smaller (8.85 vs. 14.1 cm). Statistically significant differences were found for bilaterality (63% vs. 7.3%), P=0.0001; multinodularity (55% vs. 7.3%), P=0.0001; tumor size, P=0.003; and surface involvement (50% vs. 13%), P=0.002. Five of 22 (23%) of HGSCs showed a "primary pattern" of ovarian involvement. There were no significant differences between these cases and "metastatic pattern" HGSCs when comparing morphology

  3. Retracing Memories

    ERIC Educational Resources Information Center

    Harrison, David L.

    2005-01-01

    There are plenty of paths to poetry but few are as accessible as retracing ones own memories. When students are asked to write about something they remember, they are given them the gift of choosing from events that are important enough to recall. They remember because what happened was funny or scary or embarrassing or heartbreaking or silly.…

  4. Fueling Memories

    PubMed Central

    Powell, Jonathan D.; Pollizzi, Kristen

    2012-01-01

    A hallmark of the adaptive immune response is rapid and robust activation upon rechallenge. In the current issue of Immunity van der Windt et al. (2012) provide an important link between mitochondrial respiratory capacity and the development of CD8+ T cell memory. PMID:22284413

  5. Childhood Memories.

    ERIC Educational Resources Information Center

    Soto, Lourdes Diaz

    2001-01-01

    Describes how artwork can be a valuable catalyst for discussions in preservice education classes, allowing students to explore how their work as educators relates to their childhood memories and can be shaped by childhood experiences. Examines an art exhibition in which diverse artists depicted autobiographical text in their paintings. Discusses…

  6. Childhood Memories.

    ERIC Educational Resources Information Center

    Soto, Lourdes Diaz

    2001-01-01

    Describes how artwork can be a valuable catalyst for discussions in preservice education classes, allowing students to explore how their work as educators relates to their childhood memories and can be shaped by childhood experiences. Examines an art exhibition in which diverse artists depicted autobiographical text in their paintings. Discusses…

  7. Hollow memories

    NASA Astrophysics Data System (ADS)

    2014-04-01

    A hollow-core optical fibre filled with warm caesium atoms can temporarily store the properties of photons. Michael Sprague from the University of Oxford, UK, explains to Nature Photonics how this optical memory could be a useful building block for fibre-based quantum optics.

  8. [Cancer].

    PubMed

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer.

  9. Wnt signaling inhibits CTL memory programming.

    PubMed

    Xiao, Zhengguo; Sun, Zhifeng; Smyth, Kendra; Li, Lei

    2013-12-01

    Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory.

    PubMed

    Smith, Alexandra E; Slivicki, Richard A; Hohmann, Andrea G; Crystal, Jonathon D

    2017-03-01

    Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy-induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel.

  11. [Neural correlates of memory].

    PubMed

    Fujii, Toshikatsu

    2013-01-01

    Memory can be divided into several types, although all of them involve three successive processes: encoding, storage, and retrieval. In terms of the duration of retention, neurologists classify memory into immediate, recent, and remote memories, whereas psychologists classify memory into short-term and long-term memories. In terms of the content, episodic, semantic, and procedural memories are considered to be different types of memory. Furthermore, researchers on memory have proposed relatively new concepts of memory, i.e., working memory and prospective memory. This article first provides explanations for these several types of memory. Next, neuropsychological characteristics of amnesic syndrome are briefly outlined. Finally, how several different types of memory are affected (or preserved) in patients with amnesic syndrome is described.

  12. Cancer: Unique to Older Adults

    MedlinePlus

    ... improve significantly with treatment. Changes in Thinking or Memory Some people who are treated for cancer experience “ ... helpful in cancer pain. These include: acupuncture biofeedback hypnosis heat or cold applications massage imagery meditation relaxation ...

  13. Mechanisms of Memory.

    ERIC Educational Resources Information Center

    Squire, Larry R.

    1986-01-01

    Focuses on the brain processes and brain systems involved in learning and memory from a neuropsychological perspective of analysis. Reports findings related to the locus of memory storage, types of memory and knowledge, and memory consolidation. Models of animal memory are also examined. An extensive reference list is included. (ML)

  14. From Memories to Diaries: A Portrait of Hope Captured from the Lens of a Nurse Educator as a Breast Cancer Patient

    ERIC Educational Resources Information Center

    de Guzman, Allan B.; dela Rosa, Praxedes SM; Catambay, Dexter Jayrald S.; Centeno, Angelica M.; Cheng, Lorenze Anthony A.; Castro, Jonathan Agustin R.

    2009-01-01

    Breast cancer is the most common malignancy affecting women worldwide. While it is true that hope influences how these victims view and live their lives, little is known as to how hope is lived and experienced by a breast cancer patient whose professional background and practice is nursing. This narrative-interpretive study purports to create a…

  15. From Memories to Diaries: A Portrait of Hope Captured from the Lens of a Nurse Educator as a Breast Cancer Patient

    ERIC Educational Resources Information Center

    de Guzman, Allan B.; dela Rosa, Praxedes SM; Catambay, Dexter Jayrald S.; Centeno, Angelica M.; Cheng, Lorenze Anthony A.; Castro, Jonathan Agustin R.

    2009-01-01

    Breast cancer is the most common malignancy affecting women worldwide. While it is true that hope influences how these victims view and live their lives, little is known as to how hope is lived and experienced by a breast cancer patient whose professional background and practice is nursing. This narrative-interpretive study purports to create a…

  16. Memory effects in turbulence

    NASA Technical Reports Server (NTRS)

    Hinze, J. O.

    1979-01-01

    Experimental investigations of the wake flow of a hemisphere and cylinder show that such memory effects can be substantial and have a significant influence on momentum transport. Memory effects are described in terms of suitable memory functions.

  17. Cognitive function and patient-reported memory problems after radiotherapy for cancers at the skull base: A cross-sectional survivorship study using the Telephone Interview for Cognitive Status and the MD Anderson Symptom Inventory-Head and Neck Module.

    PubMed

    Hansen, Chase C; Smith, Joshua B; Mohamed, Abdallah S R; Mulcahy, Collin F; Wefel, Jeffrey S; Hutcheson, Katherine A; Chrane, Kelsey; Phan, Jack; Frank, Steven J; Garden, Adam S; Smith, Blaine D; Eichelberger, Hillary; Anderson, Carthal; McCoy, Colton; Horiates, Marina; Patrick, Conner; Floris, Sarah; French, Chloe; Beadle, Beth M; Morrison, William H; Su, Shirley Y; Lewis, Carol M; Kupferman, Michael E; Johnson, Jason M; Skinner, Heath D; Lai, Stephen Y; Hanna, Ehab Y; Rosenthal, David I; Fuller, Clifton D; Gunn, G Brandon

    2017-10-01

    Using patient-reported and objective assessment tools, we sought to quantify cognitive symptoms and objective cognitive dysfunction in patients irradiated for skull base cancer. Participants were assessed using the Telephone Interview for Cognitive Status (TICS) and the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN), with subsequent analysis. Of the 122 participants analyzed, the majority (63%) had no frank detectable cognitive impairment by TICS, with frank impairment in 6%. Overall, mean patient-reported problems with memory (MDASImemory ) was 3.3 (SD ±2.66). On recursive partition analysis, the MDASImemory cutoff point of ≥5 was associated with detectable cognitive impairment by TICS (logworth 1.69; P = .02), yet no MDASImemory threshold was associated with unambiguous absence of impairment by TICS. Approximately one third of patients had ambiguous results by TICS assessment, for whom more rigorous testing may be warranted. Moderate to severe levels of patient-reported memory complaints on the MDASI-HN module may have utility as a screening tool for cognitive dysfunction in this population. © 2017 Wiley Periodicals, Inc.

  18. A Beginner's Guide to Memory.

    ERIC Educational Resources Information Center

    Hughes, Elizabeth M.

    1981-01-01

    This article is designed to equip the reader with the information needed to deal with questions of computer memory. Discussed are core memory; semiconductor memory; size of memory; expanding memory; charge-coupled device memories; magnetic bubble memory; and read-only and read-mostly memories. (KC)

  19. [Surgical treatment of cancer at the beginning of the third millenium--based on the 2004 Krompecher Memorial Lecture of the Society of Hungarian Oncologists].

    PubMed

    Balogh, Adám

    2010-06-01

    The author presents a historical overview of cancer surgery of the last century. At the last quarter of the century the main characteristic of this process has been the significant extension of surgical radicality. Three new surgical methods appeared and have been routinely used at the Surgical Clinic of the Szeged University School, to increase surgical radicality, to improve survival rate without impairing the postoperative quality of life. 1.) Subtotal colectomy (STC) involves an extended resection of the colon over the splenic flexure. In a period of 8 years a total of 72 STCs were performed for the treatment of large bowel obstructions or symptomatic stenosis caused by cancer of the left colon. STC offers: a) one stage treatment for colonic obstruction in emergency surgery, b.) removal of the tumor with sufficient oncological radicality, c.) primary reconstruction of the digestive tract, with a safe ileocolic anastomosis even in emergency cases. Based on a study about postoperative quality of life of STC operated patients, it proved to be normal. 2.) The author reports a total of 108 middle and low third rectal cancer cases operated on by total mesorectal excision (TME) by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The author succeeded in 60% of cases to perform an anterior resection with preservation of the anal sphincter, and to decrease the early (within two years after surgery) local recurrence rate from 14.5% to 6.4%, compared to the group of patients operated on by traditional technic. 3.) A total of 154 patients with locally advanced - stage IV - colorectal cancer underwent extended surgery of multivisceral resections as a treatment of cancer process involving adjacent abdominal organs. Surgery was performed to treat advanced cancer of the colon in 112 cases and the one of the rectum in 42 cases. The mortality rate was 7% in the colon cancer group, and 12% in the group of

  20. Memory Retrieval and Interference: Working Memory Issues

    ERIC Educational Resources Information Center

    Radvansky, Gabriel A.; Copeland, David E.

    2006-01-01

    Working memory capacity has been suggested as a factor that is involved in long-term memory retrieval, particularly when that retrieval involves a need to overcome some sort of interference (Bunting, Conway, & Heitz, 2004; Cantor & Engle, 1993). Previous work has suggested that working memory is related to the acquisition of information during…

  1. Atomic memory

    NASA Astrophysics Data System (ADS)

    Brewer, R. G.; Hahn, E. L.

    1984-12-01

    The fundamental principles of atomic-memory effects related to the Loschmidt paradox in the second law of thermodynamics are introduced and illustrated with simple analogies, photographs, and diagrams; and the results of RF and laser experiments are summarized. Nuclear-spin echoes in response to RF pulses and the NMR free-induction decay phenomenon are described, and the extension of these concepts to the visible spectrum in laser-frequency-switching and multipulsed-laser experiments is examined with an emphasis on studies of free-induction decay in LaF3 crystals containing Pr impurities (DeVoe and Brewster). The laser-induced phenomena can be applied to studies of intramolecular and intermolecular interactions, and an improved understanding of the RF effects is needed to enhance the performance of medical NMR imaging systems.

  2. Optical memory

    DOEpatents

    Mao, Samuel S; Zhang, Yanfeng

    2013-07-02

    Optical memory comprising: a semiconductor wire, a first electrode, a second electrode, a light source, a means for producing a first voltage at the first electrode, a means for producing a second voltage at the second electrode, and a means for determining the presence of an electrical voltage across the first electrode and the second electrode exceeding a predefined voltage. The first voltage, preferably less than 0 volts, different from said second voltage. The semiconductor wire is optically transparent and has a bandgap less than the energy produced by the light source. The light source is optically connected to the semiconductor wire. The first electrode and the second electrode are electrically insulated from each other and said semiconductor wire.

  3. Order-memory and association-memory.

    PubMed

    Caplan, Jeremy B

    2015-09-01

    Two highly studied memory functions are memory for associations (items presented in pairs, such as SALT-PEPPER) and memory for order (a list of items whose order matters, such as a telephone number). Order- and association-memory are at the root of many forms of behaviour, from wayfinding, to language, to remembering people's names. Most researchers have investigated memory for order separately from memory for associations. Exceptions to this, associative-chaining models build an ordered list from associations between pairs of items, quite literally understanding association- and order-memory together. Alternatively, positional-coding models have been used to explain order-memory as a completely distinct function from association-memory. Both classes of model have found empirical support and both have faced serious challenges. I argue that models that combine both associative chaining and positional coding are needed. One such hybrid model, which relies on brain-activity rhythms, is promising, but remains to be tested rigourously. I consider two relatively understudied memory behaviours that demand a combination of order- and association-information: memory for the order of items within associations (is it William James or James William?) and judgments of relative order (who left the party earlier, Hermann or William?). Findings from these underexplored procedures are already difficult to reconcile with existing association-memory and order-memory models. Further work with such intermediate experimental paradigms has the potential to provide powerful findings to constrain and guide models into the future, with the aim of explaining a large range of memory functions, encompassing both association- and order-memory. (c) 2015 APA, all rights reserved).

  4. Emotional memory persists longer than event memory.

    PubMed

    Kuriyama, Kenichi; Soshi, Takahiro; Fujii, Takeshi; Kim, Yoshiharu

    2010-03-01

    The interaction between amygdala-driven and hippocampus-driven activities is expected to explain why emotion enhances episodic memory recognition. However, overwhelming behavioral evidence regarding the emotion-induced enhancement of immediate and delayed episodic memory recognition has not been obtained in humans. We found that the recognition performance for event memory differs from that for emotional memory. Although event recognition deteriorated equally for episodes that were or were not emotionally salient, emotional recognition remained high for only stimuli related to emotional episodes. Recognition performance pertaining to delayed emotional memory is an accurate predictor of the context of past episodes.

  5. Memory and Aging

    MedlinePlus

    ... meet your neighbor for coffee? Episodic memory, which captures the “what,” “where,” and “when” of our daily ... This type of memory also includes vocabulary and knowledge of language. In addition, procedural memory, your memory ...

  6. What Is Colorectal Cancer?

    MedlinePlus

    ... Lodge® Lodging Rides To Treatment Online Support Communities ACS FUNDRAISERS Making Strides Against Breast Cancer Walks Coaches ... Give Memorial Giving Planned Giving Leadership Giving About ACS Contact Us Local Offices Employment Become a Supplier ...

  7. Maintaining memories by reactivation.

    PubMed

    Rasch, Björn; Born, Jan

    2007-12-01

    According to a widely held concept, the formation of long-term memories relies on a reactivation and redistribution of newly acquired memory representations from temporary storage to neuronal networks supporting long-term storage. Here, we review evidence showing that this process of system consolidation takes place preferentially during sleep as an 'off-line' period during which memories are spontaneously reactivated and redistributed in the absence of interfering external inputs. Moreover, postlearning sleep leads to a reorganization of neuronal representations and qualitative changes of memory content. We propose that memory reactivations during sleep are accompanied by a transient destabilization of memory traces. Unlike wake reactivations that form part of an updating of memories with respect to current perceptual input, reactivations during sleep allow for gradually adapting newly acquired memories to pre-existing long-term memories whereby invariants and certain other features of these memories become extracted.

  8. Memory Metals

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Under contract to NASA during preparations for the space station, Memry Technologies Inc. investigated shape memory effect (SME). SME is a characteristic of certain metal alloys that can change shape in response to temperature variations. In the late 1980s and early 1990s, Memry used its NASA-acquired expertise to produce a line of home and industrial safety products, and refined the technology in the mid-1990s. Among the new products they developed are three MemrySafe units which prevent scalding from faucets. Each system contains a small valve that reacts to temperature, not pressure. When the water reaches dangerous temperatures, the unit reduces the flow to a trickle; when the scalding temperature subsides, the unit restores normal flow. Other products are the FIRECHEK 2 and 4, heat-activated shutoff valves for industrial process lines, which sense excessive heat and cut off pneumatic pressure. The newest of these products is Memry's Demand Management Water Heater which shifts the electricity requirement from peak to off-peak demands, conserving energy and money.

  9. Randomized controlled trial of increasing physical activity on objectively measured and self-reported cognitive functioning among breast cancer survivors: The memory & motion study.

    PubMed

    Hartman, Sheri J; Nelson, Sandahl H; Myers, Emily; Natarajan, Loki; Sears, Dorothy D; Palmer, Barton W; Weiner, Lauren S; Parker, Barbara A; Patterson, Ruth E

    2017-09-19

    Increasing physical activity can improve cognition in healthy and cognitively impaired adults; however, the benefits for cancer survivors are unknown. The current study examined a 12-week physical activity intervention, compared with a control condition, on objective and self-reported cognition among breast cancer survivors. Sedentary breast cancer survivors were randomized to an exercise arm (n = 43) or a control arm (n = 44). At baseline and at 12 weeks, objective cognition was measured with the National Institutes of Health Cognitive Toolbox, and self-reported cognition using the Patient-Reported Outcomes Measurement Information System scales. Linear mixed-effects regression models tested intervention effects for changes in cognition scores. On average, participants (n = 87) were aged 57 years (standard deviation, 10.4 years) and were 2.5 years (standard deviation, 1.3 years) post surgery. Scores on the Oral Symbol Digit subscale (a measure of processing speed) evidenced differential improvement in the exercise arm versus the control arm (b = 2.01; P < .05). The between-group differences in improvement on self-reported cognition were not statistically significant but were suggestive of potential group differences. Time since surgery moderated the correlation, and participants who were ≤2 years post surgery had a significantly greater improvement in Oral Symbol Digit score (exercise vs control (b = 4.00; P < .01), but no significant improvement was observed in patients who were >2 years postsurgery (b = -1.19; P = .40). A significant dose response was observed with greater increased physical activity associated with objective and self-reported cognition in the exercise arm. The exercise intervention significantly improved processing speed, but only among those who had been diagnosed with breast cancer within the past 2 years. Slowed processing speed can have substantial implications for independent functioning, supporting the

  10. Memory distortion and false memory creation.

    PubMed

    Loftus, E F

    1996-01-01

    The 1990s have brought to public attention thousands of cases that began when a grown-up daughter or son walked into a therapist's office seeking help for depression, low self-esteem, or any of a number of life's problems. Many of these cases grew to involve memories of childhood sexual abuse recovered while in therapy--memories that did not exist, or at least were not remembered, before therapy began. Many of these cases also involved families torn violently apart. What should we make of these new-found memories? Are they true memories that were successfully revived in therapy? Are they false memories that were unwittingly planted? Are they symbolic expressions--historically false but representing some deep underlying truth? Insights from cognitive psychology may shed some light. Much of the litigation that has resulted from the emergence of "repressed memories" has been hazardous to the patients, and their families, as well as to the therapists who treat them.

  11. Memory beyond expression.

    PubMed

    Delorenzi, A; Maza, F J; Suárez, L D; Barreiro, K; Molina, V A; Stehberg, J

    2014-01-01

    The idea that memories are not invariable after the consolidation process has led to new perspectives about several mnemonic processes. In this framework, we review our studies on the modulation of memory expression during reconsolidation. We propose that during both memory consolidation and reconsolidation, neuromodulators can determine the probability of the memory trace to guide behavior, i.e. they can either increase or decrease its behavioral expressibility without affecting the potential of persistent memories to be activated and become labile. Our hypothesis is based on the findings that positive modulation of memory expression during reconsolidation occurs even if memories are behaviorally unexpressed. This review discusses the original approach taken in the studies of the crab Neohelice (Chasmagnathus) granulata, which was then successfully applied to test the hypothesis in rodent fear memory. Data presented offers a new way of thinking about both weak trainings and experimental amnesia: memory retrieval can be dissociated from memory expression. Furthermore, the strategy presented here allowed us to show in human declarative memory that the periods in which long-term memory can be activated and become labile during reconsolidation exceeds the periods in which that memory is expressed, providing direct evidence that conscious access to memory is not needed for reconsolidation. Specific controls based on the constraints of reminders to trigger reconsolidation allow us to distinguish between obliterated and unexpressed but activated long-term memories after amnesic treatments, weak trainings and forgetting. In the hypothesis discussed, memory expressibility--the outcome of experience-dependent changes in the potential to behave--is considered as a flexible and modulable attribute of long-term memories. Expression seems to be just one of the possible fates of re-activated memories.

  12. Problems of neural memory

    NASA Astrophysics Data System (ADS)

    Mikaelian, Andrei L.

    2005-01-01

    The paper considers the neural memory of the human brain from the viewpoint of visual information processing. A model that explains the principle of data recording and storing, memory relaxation, associative remembering and other memory functions is offered. The model of associative memory is based on the methods of holography, "wave biochemistry" and autowaves. Brief consideration is given to the associative properties of holographic neural structures and the memory architecture using running chemical reactions. The paper also outlines the problem of developing artificial memory elements for restoring the brain functions and possible interface devices for coupling neurons to electronic systems.

  13. Benzodiazepines and memory

    PubMed Central

    Roth, T.; Roehrs, T.; Wittig, R.; Zorick, F.

    1984-01-01

    1 Benzodiazepines possess anterograde amnesic properties, disrupting both short-term and long-term memory function. 2 The amount of amnesia is systematically related to dose effects and half-life differences among the benzodiazepines. 3 Memory deficits are found for episodic, semantic, and iconic memory function. 4 The deficits in long-term memory are probably the result of a disruption of consolidation of information in memory and not retrieval from memory. The disruption is produced by rapid sleep onset. 5 Thus the long-term amnesia is really a retrograde effect of sleep and not the anterograde effect of the drug. PMID:6151849

  14. Hippocampal and Cognitive Function, Exercise, and Ovarian Cancer: A Pilot Study

    DTIC Science & Technology

    2015-08-01

    the hippocampus and subsequently offset memory decline. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF... hippocampus and subsequently offset memory decline. 2 KEYWORDS: Physical activity interventions, ovarian cancer treatment, chemotherapy-induced...chemotherapy complaint in a single cancer: problems with memory in patients with ovarian cancer. We focus on this problem for three reasons: 1

  15. Weekly paclitaxel in women with heavily pretreated metastatic breast cancer: a retrospective analysis of cases treated at the Chang Gung Memorial Hospital.

    PubMed

    Lu, Chang-Hsien; Lin, Yung-Chang; Chang, Hsien-Kun

    2007-01-01

    Taxane is one of the most effective drugs used for advanced metastatic breast cancer treatment. Conventional 3-weekly regimens are widely used with significant treatment related toxicity. Recently, weekly schedules of taxane were reported to be effective and well tolerated in this patient group. We retrospectively evaluated the efficacy of weekly paclitaxel in women with metastatic breast cancer. Between December 1999 and June 2004, a total of twenty-three patients with histologically confirmed and measurable pretreated metastatic breast cancer were included. The median age was 55 years (range 33 to approximately 73). Their performance status was ECOG < or = 2. All patients had received at least one regimen for metastatic disease. Paclitaxel 80 mg/m2 was administered weekly for 3 weeks per 4-week cycle. WHO response criteria was used as the reference to evaluate the response to treatment. The response and survival of all patients were assessed. All had prior anthracycline-based chemotherapy; 14 patients (61%) had at least 3 different chemotherapy lines before this regimen. Twenty patients (87%) had at least 2 metastatic sites and 18 (78.3%) had visceral metastasis. The overall response rate was 21.7% with no complete response, while 43.5% had stable disease. The median time to progression was 121 days. Four patients (17.4%) were treated with a trastuzumab-paclitaxel combination, and 2 of them responded. The therapy was well tolerated and there were no grade III/IV toxicities observed. Only 1 patient (4.35%) dropped out because of heart failure. Weekly paclitaxel was well tolerated and the response rate was comparable to that previously reported in heavily pretreated patients with metastatic breast cancer. Weekly paclitaxel in combination with other agents is worthy of further investigation.

  16. Searching for repressed memory.

    PubMed

    McNally, Richard J

    2012-01-01

    This chapter summarizes the work of my research group on adults who report either repressed, recovered, or continuous memories of childhood sexual abuse (CSA) or who report no history of CSA. Adapting paradigms from cognitive psychology, we tested hypotheses inspired by both the "repressed memory" and "false memory" perspectives on recovered memories of CSA. We found some evidence for the false memory perspective, but no evidence for the repressed memory perspective. However, our work also suggests a third perspective on recovered memories that does not require the concept of repression. Some children do not understand their CSA when it occurs, and do not experience terror. Years later, they recall the experience, and understanding it as abuse, suffer intense distress. The memory failed to come to mind for years, partly because the child did not encode it as terrifying (i.e., traumatic), not because the person was unable to recall it.

  17. Emotional Memory Persists Longer than Event Memory

    ERIC Educational Resources Information Center

    Kuriyama, Kenichi; Soshi, Takahiro; Fujii, Takeshi; Kim, Yoshiharu

    2010-01-01

    The interaction between amygdala-driven and hippocampus-driven activities is expected to explain why emotion enhances episodic memory recognition. However, overwhelming behavioral evidence regarding the emotion-induced enhancement of immediate and delayed episodic memory recognition has not been obtained in humans. We found that the recognition…

  18. Emotional Memory Persists Longer than Event Memory

    ERIC Educational Resources Information Center

    Kuriyama, Kenichi; Soshi, Takahiro; Fujii, Takeshi; Kim, Yoshiharu

    2010-01-01

    The interaction between amygdala-driven and hippocampus-driven activities is expected to explain why emotion enhances episodic memory recognition. However, overwhelming behavioral evidence regarding the emotion-induced enhancement of immediate and delayed episodic memory recognition has not been obtained in humans. We found that the recognition…

  19. Music, memory and emotion.

    PubMed

    Jäncke, Lutz

    2008-08-08

    Because emotions enhance memory processes and music evokes strong emotions, music could be involved in forming memories, either about pieces of music or about episodes and information associated with particular music. A recent study in BMC Neuroscience has given new insights into the role of emotion in musical memory.

  20. Origins of Autobiographical Memory.

    ERIC Educational Resources Information Center

    Harley, Keryn; Reese, Elaine

    1999-01-01

    Tested predictions of infantile amnesia theory compared with social-interactionist account of autobiographical memory. Found maternal reminiscing style and self-recognition when child was 19 months old uniquely predicted children's shared memory reports across time, even with children's initial language and nonverbal memory factored out.…

  1. Music, memory and emotion

    PubMed Central

    Jäncke, Lutz

    2008-01-01

    Because emotions enhance memory processes and music evokes strong emotions, music could be involved in forming memories, either about pieces of music or about episodes and information associated with particular music. A recent study in BMC Neuroscience has given new insights into the role of emotion in musical memory. PMID:18710596

  2. Memory and the Self

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2005-01-01

    The Self-Memory System (SMS) is a conceptual framework that emphasizes the interconnectedness of self and memory. Within this framework memory is viewed as the data base of the self. The self is conceived as a complex set of active goals and associated self-images, collectively referred to as the "working self." The relationship between the…

  3. Memory and the Self

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2005-01-01

    The Self-Memory System (SMS) is a conceptual framework that emphasizes the interconnectedness of self and memory. Within this framework memory is viewed as the data base of the self. The self is conceived as a complex set of active goals and associated self-images, collectively referred to as the "working self." The relationship between the…

  4. Make-Believe Memories

    ERIC Educational Resources Information Center

    Loftus, Elizabeth F.

    2003-01-01

    Research on memory distortion has shown that postevent suggestion can contaminate what a person remembers. Moreover, suggestion can lead to false memories being injected outright into the minds of people. These findings have implications for police investigation, clinical practice, and other settings in which memory reports are solicited.

  5. Modification of Antigen Impacts on Memory Quality after Adenovirus Vaccination.

    PubMed

    Colston, Julia M; Bolinger, Beatrice; Cottingham, Matthew G; Gilbert, Sarah; Klenerman, Paul

    2016-04-15

    The establishment of robust T cell memory is critical for the development of novel vaccines for infections and cancers. Classical memory generated by CD8(+)T cells is characterized by contracted populations homing to lymphoid organs. T cell memory inflation, as seen for example after CMV infection, is the maintenance of expanded, functional, tissue-associated effector memory cell pools. Such memory pools may also be induced after adenovirus vaccination, and we recently defined common transcriptional and phenotypic features of these populations in mice and humans. However, the rules that govern which epitopes drive memory inflation compared with classical memory are not fully defined, and thus it is not currently possible to direct this process. We used our adenoviral model of memory inflation to first investigate the role of the promoter and then the role of the epitope context in determining memory formation. Specifically, we tested the hypothesis that conventional memory could be converted to inflationary memory by simple presentation of the Ag in the form of minigene vectors. When epitopes from LacZ and murine CMV that normally induce classical memory responses were presented as minigenes, they induced clear memory inflation. These data demonstrate that, regardless of the transgene promoter, the polypeptide context of a CD8(+)T cell epitope may determine whether classical or inflating memory responses are induced. The ability to direct this process by the use of minigenes is relevant to the design of vaccines and understanding of immune responses to pathogens. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. On-command on/off switching of progenitor cell and cancer cell polarized motility and aligned morphology via a cytocompatible shape memory polymer scaffold.

    PubMed

    Wang, Jing; Quach, Andy; Brasch, Megan E; Turner, Christopher E; Henderson, James H

    2017-09-01

    In vitro biomaterial models have enabled advances in understanding the role of extracellular matrix (ECM) architecture in the control of cell motility and polarity. Most models are, however, static and cannot mimic dynamic aspects of in vivo ECM remodeling and function. To address this limitation, we present an electrospun shape memory polymer scaffold that can change fiber alignment on command under cytocompatible conditions. Cellular response was studied using the human fibrosarcoma cell line HT-1080 and the murine mesenchymal stem cell line C3H/10T1/2. The results demonstrate successful on-command on/off switching of cell polarized motility and alignment. Decrease in fiber alignment causes a change from polarized motility along the direction of fiber alignment to non-polarized motility and from aligned to unaligned morphology, while increase in fiber alignment causes a change from non-polarized to polarized motility along the direction of fiber alignment and from unaligned to aligned morphology. In addition, the findings are consistent with the hypothesis that increased fiber alignment causes increased cell velocity, while decreased fiber alignment causes decreased cell velocity. On-command on/off switching of cell polarized motility and alignment is anticipated to enable new study of directed cell motility in tumor metastasis, in cell homing, and in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Siblings of Childhood Cancer Survivors.

    ERIC Educational Resources Information Center

    Gogan, Janis L.

    This paper reports on a long term follow up study of siblings of childhood cancer survivors. Seventy siblings of childhood cancer survivors in 37 families were interviewed using a semi-structured format which included both forced choice and open ended questions. The children discussed their memories of the sibling's cancer diagnosis and treatment…

  8. Siblings of Childhood Cancer Survivors.

    ERIC Educational Resources Information Center

    Gogan, Janis L.

    This paper reports on a long term follow up study of siblings of childhood cancer survivors. Seventy siblings of childhood cancer survivors in 37 families were interviewed using a semi-structured format which included both forced choice and open ended questions. The children discussed their memories of the sibling's cancer diagnosis and treatment…

  9. Memory: Organization and Control

    PubMed Central

    Eichenbaum, Howard

    2017-01-01

    A major goal of memory research is to understand how cognitive processes in memory are supported at the level of brain systems and network representations. Especially promising in this direction are new findings in humans and animals that converge in indicating a key role for the hippocampus in the systematic organization of memories. New findings also indicate that the prefrontal cortex may play an equally important role in the active control of memory organization during both encoding and retrieval. Observations about the dialog between the hippocampus and prefrontal cortex provide new insights into the operation of the larger brain system that serves memory. PMID:27687117

  10. Memory dynamics under stress.

    PubMed

    Quaedflieg, Conny W E M; Schwabe, Lars

    2017-06-19

    Stressful events have a major impact on memory. They modulate memory formation in a time-dependent manner, closely linked to the temporal profile of action of major stress mediators, in particular catecholamines and glucocorticoids. Shortly after stressor onset, rapidly acting catecholamines and fast, non-genomic glucocorticoid actions direct cognitive resources to the processing and consolidation of the ongoing threat. In parallel, control of memory is biased towards rather rigid systems, promoting habitual forms of memory allowing efficient processing under stress, at the expense of "cognitive" systems supporting memory flexibility and specificity. In this review, we discuss the implications of this shift in the balance of multiple memory systems for the dynamics of the memory trace. Specifically, stress appears to hinder the incorporation of contextual details into the memory trace, to impede the integration of new information into existing knowledge structures, to impair the flexible generalisation across past experiences, and to hamper the modification of memories in light of new information. Delayed, genomic glucocorticoid actions might reverse the control of memory, thus restoring homeostasis and "cognitive" control of memory again.

  11. Immunological memory is associative

    SciTech Connect

    Smith, D.J.; Forrest, S.; Perelson, A.S.

    1996-12-31

    The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.

  12. Origins of autobiographical memory.

    PubMed

    Harley, K; Reese, E

    1999-09-01

    This study tested the predictions of M. L. Howe and M. L. Courage's (1993, 1997) theory of infantile amnesia compared with a social-interactionist account of autobiographical memory development (R. Fivush & E. Reese, 1992; K. Nelson, 1993b). Fifty-eight mother-child dyads were assessed for maternal styles of talking about the past and for children's self-recognition, language production, and nonverbal memory when the children were 19 months old. Children's shared and independent memory reports were then assessed from 19 to 32 months. Maternal reminiscing style and self-recognition uniquely predicted children's shared memory reports across time, even with children's initial language and nonverbal memory factored out. Self-recognition skills also predicted children's later independent memory. These results support a pluralistic account of the origins of autobiographical memory.

  13. Flexible Kernel Memory

    PubMed Central

    Nowicki, Dimitri; Siegelmann, Hava

    2010-01-01

    This paper introduces a new model of associative memory, capable of both binary and continuous-valued inputs. Based on kernel theory, the memory model is on one hand a generalization of Radial Basis Function networks and, on the other, is in feature space, analogous to a Hopfield network. Attractors can be added, deleted, and updated on-line simply, without harming existing memories, and the number of attractors is independent of input dimension. Input vectors do not have to adhere to a fixed or bounded dimensionality; they can increase and decrease it without relearning previous memories. A memory consolidation process enables the network to generalize concepts and form clusters of input data, which outperforms many unsupervised clustering techniques; this process is demonstrated on handwritten digits from MNIST. Another process, reminiscent of memory reconsolidation is introduced, in which existing memories are refreshed and tuned with new inputs; this process is demonstrated on series of morphed faces. PMID:20552013

  14. Memory access in shared virtual memory

    SciTech Connect

    Berrendorf, R. )

    1992-01-01

    Shared virtual memory (SVM) is a virtual memory layer with a single address space on top of a distributed real memory on parallel computers. We examine the behavior and performance of SVM running a parallel program with medium-grained, loop-level parallelism on top of it. A simulator for the underlying parallel architecture can be used to examine the behavior of SVM more deeply. The influence of several parameters, such as the number of processors, page size, cold or warm start, and restricted page replication, is studied.

  15. Memory access in shared virtual memory

    SciTech Connect

    Berrendorf, R.

    1992-09-01

    Shared virtual memory (SVM) is a virtual memory layer with a single address space on top of a distributed real memory on parallel computers. We examine the behavior and performance of SVM running a parallel program with medium-grained, loop-level parallelism on top of it. A simulator for the underlying parallel architecture can be used to examine the behavior of SVM more deeply. The influence of several parameters, such as the number of processors, page size, cold or warm start, and restricted page replication, is studied.

  16. Stochastic memory: memory enhancement due to noise.

    PubMed

    Stotland, Alexander; Di Ventra, Massimiliano

    2012-01-01

    There are certain classes of resistors, capacitors, and inductors that, when subject to a periodic input of appropriate frequency, develop hysteresis loops in their characteristic response. Here we show that the hysteresis of such memory elements can also be induced by white noise of appropriate intensity even at very low frequencies of the external driving field. We illustrate this phenomenon using a physical model of memory resistor realized by TiO(2) thin films sandwiched between metallic electrodes and discuss under which conditions this effect can be observed experimentally. We also discuss its implications on existing memory systems described in the literature and the role of colored noise.

  17. Stochastic memory: Memory enhancement due to noise

    NASA Astrophysics Data System (ADS)

    Stotland, Alexander; di Ventra, Massimiliano

    2012-01-01

    There are certain classes of resistors, capacitors, and inductors that, when subject to a periodic input of appropriate frequency, develop hysteresis loops in their characteristic response. Here we show that the hysteresis of such memory elements can also be induced by white noise of appropriate intensity even at very low frequencies of the external driving field. We illustrate this phenomenon using a physical model of memory resistor realized by TiO2 thin films sandwiched between metallic electrodes and discuss under which conditions this effect can be observed experimentally. We also discuss its implications on existing memory systems described in the literature and the role of colored noise.

  18. Memory bistable mechanisms of organic memory devices

    NASA Astrophysics Data System (ADS)

    Lee, Ching-Ting; Yu, Li-Zhen; Chen, Hung-Chun

    2010-07-01

    To investigate the memory bistable mechanisms of organic memory devices, the structure of [top Au anode/9,10-di(2-naphthyl)anthracene (ADN) active layer/bottom Au cathode] was deposited using a thermal deposition system. The Au atoms migrated into the ADN active layer was observed from the secondary ion mass spectrometry. The density of 9.6×1016 cm-3 and energy level of 0.553 eV of the induced trapping centers caused by the migrated Au atoms in the ADN active layer were calculated. The induced trapping centers did not influence the carrier injection barrier height between Au and ADN active layer. Therefore, the memory bistable behaviors of the organic memory devices were attributed to the induced trapping centers. The energy diagram was established to verify the mechanisms.

  19. Reconsolidation of drug memories

    PubMed Central

    Sorg, Barbara A.

    2012-01-01

    Persistent, unwanted memories are believed to be key contributors to drug addiction and the chronic relapse problem over the lifetime of the addict. Contrary to the long-held idea that memories are static and fixed, new studies in the last decade have shown that memories are dynamic and changeable. However, they are changeable only under specific conditions. When a memory is retrieved (reactivated), it becomes labile for a period of minutes to hours and then is reconsolidated to maintain long-term memory. Recent findings indicate that even well-established long-term memories may be susceptible to disruption by interfering with reconsolidation through delivery of certain amnestic agents during memory retrieval. Here I review the growing literature on memory reconsolidation in animal models of addiction, including sensitization, conditioned place preference and self-administration. I also discuss (a) several issues that need to be considered in interpreting the findings from reconsolidation studies and (b) future challenges and directions for memory reconsolidation studies in the field of addiction. The findings indicate promise for using this approach as a therapy for disrupting the long-lasting memories that can trigger relapse. PMID:22342780

  20. Overdistribution in source memory.

    PubMed

    Brainerd, C J; Reyna, V F; Holliday, R E; Nakamura, K

    2012-03-01

    Semantic false memories are confounded with a second type of error, overdistribution, in which items are attributed to contradictory episodic states. Overdistribution errors have proved to be more common than false memories when the 2 are disentangled. We investigated whether overdistribution is prevalent in another classic false memory paradigm: source monitoring. It is. Conventional false memory responses (source misattributions) were predominantly overdistribution errors, but unlike semantic false memory, overdistribution also accounted for more than half of true memory responses (correct source attributions). Experimental control of overdistribution was achieved via a series of manipulations that affected either recollection of contextual details or item memory (concreteness, frequency, list order, number of presentation contexts, and individual differences in verbatim memory). A theoretical model was used to analyze the data (conjoint process dissociation) that predicts that (a) overdistribution is directly proportional to item memory but inversely proportional to recollection and (b) item memory is not a necessary precondition for recollection of contextual details. The results were consistent with both predictions. 2012 APA, all rights reserved

  1. Psychophysiology of prospective memory.

    PubMed

    Rothen, Nicolas; Meier, Beat

    2014-01-01

    Prospective memory involves the self-initiated retrieval of an intention upon an appropriate retrieval cue. Cue identification can be considered as an orienting reaction and may thus trigger a psychophysiological response. Here we present two experiments in which skin conductance responses (SCRs) elicited by prospective memory cues were compared to SCRs elicited by aversive stimuli to test whether a single prospective memory cue triggers a similar SCR as an aversive stimulus. In Experiment 2 we also assessed whether cue specificity had a differential influence on prospective memory performance and on SCRs. We found that detecting a single prospective memory cue is as likely to elicit a SCR as an aversive stimulus. Missed prospective memory cues also elicited SCRs. On a behavioural level, specific intentions led to better prospective memory performance. However, on a psychophysiological level specificity had no influence. More generally, the results indicate reliable SCRs for prospective memory cues and point to psychophysiological measures as valuable approach, which offers a new way to study one-off prospective memory tasks. Moreover, the findings are consistent with a theory that posits multiple prospective memory retrieval stages.

  2. Human memory B cells.

    PubMed

    Seifert, M; Küppers, R

    2016-12-01

    A key feature of the adaptive immune system is the generation of memory B and T cells and long-lived plasma cells, providing protective immunity against recurring infectious agents. Memory B cells are generated in germinal center (GC) reactions in the course of T cell-dependent immune responses and are distinguished from naive B cells by an increased lifespan, faster and stronger response to stimulation and expression of somatically mutated and affinity matured immunoglobulin (Ig) genes. Approximately 40% of human B cells in adults are memory B cells, and several subsets were identified. Besides IgG(+) and IgA(+) memory B cells, ∼50% of peripheral blood memory B cells express IgM with or without IgD. Further smaller subpopulations have additionally been described. These various subsets share typical memory B cell features, but likely also fulfill distinct functions. IgM memory B cells appear to have the propensity for refined adaptation upon restimulation in additional GC reactions, whereas reactivated IgG B cells rather differentiate directly into plasma cells. The human memory B-cell pool is characterized by (sometimes amazingly large) clonal expansions, often showing extensive intraclonal IgV gene diversity. Moreover, memory B-cell clones are frequently composed of members of various subsets, showing that from a single GC B-cell clone a variety of memory B cells with distinct functions is generated. Thus, the human memory B-cell compartment is highly diverse and flexible. Several B-cell malignancies display features suggesting a derivation from memory B cells. This includes a subset of chronic lymphocytic leukemia, hairy cell leukemia and marginal zone lymphomas. The exposure of memory B cells to oncogenic events during their generation in the GC, the longevity of these B cells and the ease to activate them may be key determinants for their malignant transformation.

  3. Human learning and memory.

    PubMed

    Johnson, M K; Hasher, L

    1987-01-01

    There have been several notable recent trends in the area of learning and memory. Problems with the episodic/semantic distinction have become more apparent, and new efforts have been made (exemplar models, distributed-memory models) to represent general knowledge without assuming a separate semantic system. Less emphasis is being placed on stable, prestored prototypes and more emphasis on a flexible memory system that provides the basis for a multitude of categories or frames of reference, derived on the spot as tasks demand. There is increasing acceptance of the idea that mental models are constructed and stored in memory in addition to, rather than instead of, memorial representations that are more closely tied to perceptions. This gives rise to questions concerning the conditions that permit inferences to be drawn and mental models to be constructed, and to questions concerning the similarities and differences in the nature of the representations in memory of perceived and generated information and in their functions. There has also been a swing from interest in deliberate strategies to interest in automatic, unconscious (even mechanistic!) processes, reflecting an appreciation that certain situations (e.g. recognition, frequency judgements, savings in indirect tasks, aspects of skill acquisition, etc) seem not to depend much on the products of strategic, effortful or reflective processes. There is a lively interest in relations among memory measures and attempts to characterize memory representations and/or processes that could give rise to dissociations among measures. Whether the pattern of results reflects the operation of functional subsystems of memory and, if so, what the "modules" are is far from clear. This issue has been fueled by work with amnesics and has contributed to a revival of interaction between researchers studying learning and memory in humans and those studying learning and memory in animals. Thus, neuroscience rivals computer science as a

  4. Conscious and unconscious memory systems.

    PubMed

    Squire, Larry R; Dede, Adam J O

    2015-03-02

    The idea that memory is not a single mental faculty has a long and interesting history but became a topic of experimental and biologic inquiry only in the mid-20th century. It is now clear that there are different kinds of memory, which are supported by different brain systems. One major distinction can be drawn between working memory and long-term memory. Long-term memory can be separated into declarative (explicit) memory and a collection of nondeclarative (implicit) forms of memory that include habits, skills, priming, and simple forms of conditioning. These memory systems depend variously on the hippocampus and related structures in the parahippocampal gyrus, as well as on the amygdala, the striatum, cerebellum, and the neocortex. This work recounts the discovery of declarative and nondeclarative memory and then describes the nature of declarative memory, working memory, nondeclarative memory, and the relationship between memory systems. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Conscious and Unconscious Memory Systems

    PubMed Central

    Squire, Larry R.; Dede, Adam J.O.

    2015-01-01

    The idea that memory is not a single mental faculty has a long and interesting history but became a topic of experimental and biologic inquiry only in the mid-20th century. It is now clear that there are different kinds of memory, which are supported by different brain systems. One major distinction can be drawn between working memory and long-term memory. Long-term memory can be separated into declarative (explicit) memory and a collection of nondeclarative (implicit) forms of memory that include habits, skills, priming, and simple forms of conditioning. These memory systems depend variously on the hippocampus and related structures in the parahippocampal gyrus, as well as on the amygdala, the striatum, cerebellum, and the neocortex. This work recounts the discovery of declarative and nondeclarative memory and then describes the nature of declarative memory, working memory, nondeclarative memory, and the relationship between memory systems. PMID:25731765

  6. A generalized memory test algorithm

    NASA Technical Reports Server (NTRS)

    Milner, E. J.

    1982-01-01

    A general algorithm for testing digital computer memory is presented. The test checks that (1) every bit can be cleared and set in each memory work, and (2) bits are not erroneously cleared and/or set elsewhere in memory at the same time. The algorithm can be applied to any size memory block and any size memory word. It is concise and efficient, requiring the very few cycles through memory. For example, a test of 16-bit-word-size memory requries only 384 cycles through memory. Approximately 15 seconds were required to test a 32K block of such memory, using a microcomputer having a cycle time of 133 nanoseconds.

  7. Memory-controlled diffusion

    NASA Astrophysics Data System (ADS)

    Trimper, Steffen; Zabrocki, Knud; Schulz, Michael

    2004-11-01

    Memory effects require for their incorporation into random-walk models an extension of the conventional equations. The linear Fokker-Planck equation for the probability density p(r⃗,t) is generalized by including nonlinear and nonlocal spatial-temporal memory effects. The realization of the memory kernel is restricted due the conservation of the basic quantity p . A general criteria is given for the existence of stationary solutions. In case the memory kernel depends on p polynomially, transport may be prevented. Owing to the delay effects a finite amount of particles remains localized and the further transport is terminated. For diffusion with nonlinear memory effects we find an exact solution in the long-time limit. Although the mean square displacement exhibits diffusive behavior, higher order cumulants offer differences to diffusion and they depend on the memory strength.

  8. Shape memory polymers

    DOEpatents

    Wilson, Thomas S.; Bearinger, Jane P.

    2017-08-29

    New shape memory polymer compositions, methods for synthesizing new shape memory polymers, and apparatus comprising an actuator and a shape memory polymer wherein the shape memory polymer comprises at least a portion of the actuator. A shape memory polymer comprising a polymer composition which physically forms a network structure wherein the polymer composition has shape-memory behavior and can be formed into a permanent primary shape, re-formed into a stable secondary shape, and controllably actuated to recover the permanent primary shape. Polymers have optimal aliphatic network structures due to minimization of dangling chains by using monomers that are symmetrical and that have matching amine and hydroxl groups providing polymers and polymer foams with clarity, tight (narrow temperature range) single transitions, and high shape recovery and recovery force that are especially useful for implanting in the human body.

  9. Shape memory polymers

    DOEpatents

    Wilson, Thomas S.; Bearinger, Jane P.

    2015-06-09

    New shape memory polymer compositions, methods for synthesizing new shape memory polymers, and apparatus comprising an actuator and a shape memory polymer wherein the shape memory polymer comprises at least a portion of the actuator. A shape memory polymer comprising a polymer composition which physically forms a network structure wherein the polymer composition has shape-memory behavior and can be formed into a permanent primary shape, re-formed into a stable secondary shape, and controllably actuated to recover the permanent primary shape. Polymers have optimal aliphatic network structures due to minimization of dangling chains by using monomers that are symmetrical and that have matching amine and hydroxyl groups providing polymers and polymer foams with clarity, tight (narrow temperature range) single transitions, and high shape recovery and recovery force that are especially useful for implanting in the human body.

  10. Does fascia hold memories?

    PubMed

    Tozzi, Paolo

    2014-04-01

    The idea that tissues may possess some sort of memory is a controversial topic in manual medicine, calling for research and clinical exploration. Many bodyworkers, at some point in their practice, have experienced phenomena that may be interpreted as representing a release of memory traces when working on dysfunctional tissues. This feeling may have been accompanied by some type of sensory experience, for the therapist and/or the patient. In some cases, early traumatic experiences may be recalled. When this happens, the potency of the memory may be erased or eased, along with restoration of tissue function. Hence the questions: can memories be held in the fascia? And: are these memories accessible during manual fascial work? Modern research has proposed a variety of different interpretations as to how memory might be stored in soft tissues, possibly involving other forms of information storage not exclusively processed neurologically (Box 1). Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Regulatory T cell memory

    PubMed Central

    Rosenblum, Michael D.; Way, Sing Sing; Abbas, Abul K.

    2016-01-01

    Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime challenge models of infection. However, recent work has also identified persistently expanded populations of antigen-specific regulatory T cells that protect against aberrant immune responses. In this Review, we consider the parallels between memory effector T cells and memory regulatory T cells, along with the functional implications of regulatory memory in autoimmunity, antimicrobial host defence and maternal fetal tolerance. In addition, we discuss emerging evidence for regulatory T cell memory in humans and key unanswered questions in this rapidly evolving field. PMID:26688349

  12. Psychopharmacology and memory

    PubMed Central

    Glannon, W

    2006-01-01

    Psychotropic and other drugs can alter brain mechanisms regulating the formation, storage, and retrieval of different types of memory. These include “off label” uses of existing drugs and new drugs designed specifically to target the neural bases of memory. This paper discusses the use of beta‐adrenergic antagonists to prevent or erase non‐conscious pathological emotional memories in the amygdala. It also discusses the use of novel psychopharmacological agents to enhance long term semantic and short term working memory by altering storage and retrieval mechanisms in the hippocampus and prefrontal cortex. Although intervention in the brain to alter memory as therapy or enhancement holds considerable promise, the long term effects of experimental drugs on the brain and memory are not known. More studies are needed to adequately assess the potential benefits and risks of these interventions. PMID:16446410

  13. Myrmics Memory Allocator

    SciTech Connect

    Lymperis, S.

    2011-09-23

    MMA is a stand-alone memory management system for MPI clusters. It implements a shared Partitioned Global Address Space, where multiple MPI processes request objects from the allocator and the latter provides them with system-wide unique memory addresses for each object. It provides applications with an intuitive way of managing the memory system in a unified way, thus enabling easier writing of irregular application code.

  14. Content Addressable Memory Project

    DTIC Science & Technology

    1990-11-01

    The Content Addressable M1-emory Project consists of the development of several experimental software systems on an AMT Distributed Array Processor...searching (database) compiler algorithms memory management other systems software) Linear C is an unlovely hybrid language which imports the CAM...memory from AMT’s operating system for the DAP; how- ever, other than this limitation, the memory management routines work exactly as their C counterparts

  15. Sparse distributed memory

    NASA Technical Reports Server (NTRS)

    Kanerva, Pentti

    1988-01-01

    Theoretical models of the human brain and proposed neural-network computers are developed analytically. Chapters are devoted to the mathematical foundations, background material from computer science, the theory of idealized neurons, neurons as address decoders, and the search of memory for the best match. Consideration is given to sparse memory, distributed storage, the storage and retrieval of sequences, the construction of distributed memory, and the organization of an autonomous learning system.

  16. Magnetic bubble domain memories

    NASA Technical Reports Server (NTRS)

    Ypma, J. E.

    1974-01-01

    Some attractive features of Bubble Domain Memory and its relation to existing technologies are discussed. Two promising applications are block access mass memory and tape recorder replacement. The required chip capabilities for these uses are listed, and the specifications for a block access mass memory designed to fit between core and HPT disk are presented. A feasibility model for a tape recorder replacement is introduced.

  17. Random Access Memory Technologies.

    DTIC Science & Technology

    1985-02-01

    extreme temperatures. True nonvolatility is offered by the NVRAM or shadow RAM. In the NVRAM , a volatile NMOS static RAM memory cell is merged with the...or reapplied, and no longer require special power sources. The size of the nine-device memory cell required for the NVRAM has limited its capacity to...4K. While 8K NVRAMs are expected in 1985, the 30 . . .’o .-. . high cost of these devices will hamper further development for larger capacity memories

  18. Sparse distributed memory

    SciTech Connect

    Kanerva, P.

    1988-01-01

    Theoretical models of the human brain and proposed neural-network computers are developed analytically. Chapters are devoted to the mathematical foundations, background material from computer science, the theory of idealized neurons, neurons as address decoders, and the search of memory for the best match. Consideration is given to sparse memory, distributed storage, the storage and retrieval of sequences, the construction of distributed memory, and the organization of an autonomous learning system. 63 refs.

  19. Memory Load and Dump

    NASA Astrophysics Data System (ADS)

    Welty, Alan

    2009-07-01

    This proposal is a test and verification of the STIS dump of memory capability.Areas of Control Section {CS} to dump include: EDAC RAM, EEPROM, and CS PROM {with the CS in Operate}. Areas of MIE memory to dump include: MIE RAM and MIE PROM {with the MIE in Operate}. Note that the MIE memory must first be copied to CS buffer RAM as images, which are then dumped.Supports Activity STIS-02

  20. Memory Golf Clubs

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Memory Corporation's investigation of shape memory effect, stemming from Marshall Space Flight Center contracts to study materials for the space station, has aided in the development of Zeemet, a proprietary, high-damping shape memory alloy for the golf industry. The Nicklaus Golf Company has created a new line of golf clubs using Zeemet inserts. Its superelastic and high damping attributes translate into more spin on the ball, greater control, and a solid feel.

  1. Sparse distributed memory

    NASA Technical Reports Server (NTRS)

    Kanerva, Pentti

    1988-01-01

    Theoretical models of the human brain and proposed neural-network computers are developed analytically. Chapters are devoted to the mathematical foundations, background material from computer science, the theory of idealized neurons, neurons as address decoders, and the search of memory for the best match. Consideration is given to sparse memory, distributed storage, the storage and retrieval of sequences, the construction of distributed memory, and the organization of an autonomous learning system.

  2. Myrmics Memory Allocator

    SciTech Connect

    Lymperis, S.

    2011-09-23

    MMA is a stand-alone memory management system for MPI clusters. It implements a shared Partitioned Global Address Space, where multiple MPI processes request objects from the allocator and the latter provides them with system-wide unique memory addresses for each object. It provides applications with an intuitive way of managing the memory system in a unified way, thus enabling easier writing of irregular application code.

  3. Networks of Memories

    DTIC Science & Technology

    2013-03-01

    2000). The construction of  autobiographical   memories in the self­memory system. Psychological Review, 107(2), 261­288. Dennis, S., & Chapman, A. (2010...AFRL-OSR-VA-TR-2013-0131 Networks of Memories Simon Dennis, Mikhail Belkin Ohio State University March 2013 Final...Back (Rev. 8/98) 1 Networks of  Memories FA9550­09­1­0614 Professor Jay Myung PI: Simon Dennis Ohio State University February 15, 2013 2 Introduction

  4. The future of memory

    NASA Astrophysics Data System (ADS)

    Marinella, M.

    In the not too distant future, the traditional memory and storage hierarchy of may be replaced by a single Storage Class Memory (SCM) device integrated on or near the logic processor. Traditional magnetic hard drives, NAND flash, DRAM, and higher level caches (L2 and up) will be replaced with a single high performance memory device. The Storage Class Memory paradigm will require high speed (< 100 ns read/write), excellent endurance (> 1012), nonvolatility (retention > 10 years), and low switching energies (< 10 pJ per switch). The International Technology Roadmap for Semiconductors (ITRS) has recently evaluated several potential candidates SCM technologies, including Resistive (or Redox) RAM, Spin Torque Transfer RAM (STT-MRAM), and phase change memory (PCM). All of these devices show potential well beyond that of current flash technologies and research efforts are underway to improve the endurance, write speeds, and scalabilities to be on-par with DRAM. This progress has interesting implications for space electronics: each of these emerging device technologies show excellent resistance to the types of radiation typically found in space applications. Commercially developed, high density storage class memory-based systems may include a memory that is physically radiation hard, and suitable for space applications without major shielding efforts. This paper reviews the Storage Class Memory concept, emerging memory devices, and possible applicability to radiation hardened electronics for space.

  5. Hypnosis, memory and amnesia.

    PubMed Central

    Kihlstrom, J F

    1997-01-01

    Hypnotized subjects respond to suggestions from the hypnotist for imaginative experiences involving alterations in perception and memory. Individual differences in hypnotizability are only weakly related to other forms of suggestibility. Neuropsychological speculations about hypnosis focus on the right hemisphere and/or the frontal lobes. Posthypnotic amnesia refers to subjects' difficulty in remembering, after hypnosis, the events and experiences that transpired while they were hypnotized. Posthypnotic amnesia is not an instance of state-dependent memory, but it does seem to involve a disruption of retrieval processes similar to the functional amnesias observed in clinical dissociative disorders. Implicit memory, however, is largely spared, and may underlie subjects' ability to recognize events that they cannot recall. Hypnotic hypermnesia refers to improved memory for past events. However, such improvements are illusory: hypermnesia suggestions increase false recollection, as well as subjects' confidence in both true and false memories. Hypnotic age regression can be subjectively compelling, but does not involve the ablation of adult memory, or the reinstatement of childlike modes of mental functioning, or the revivification of memory. The clinical and forensic use of hypermnesia and age regression to enhance memory in patients, victims and witnesses (e.g. recovered memory therapy for child sexual abuse) should be discouraged. PMID:9415925

  6. Retrieval of Emotional Memories

    PubMed Central

    Buchanan, Tony W.

    2008-01-01

    Long-term memories are influenced by the emotion experienced during learning as well as by the emotion experienced during memory retrieval. The present article reviews the literature addressing the effects of emotion on retrieval, focusing on the cognitive and neurological mechanisms that have been revealed. The reviewed research suggests that the amygdala, in combination with the hippocampus and prefrontal cortex, plays an important role in the retrieval of memories for emotional events. The neural regions necessary for online emotional processing also influence emotional memory retrieval, perhaps through the reexperience of emotion during the retrieval process. PMID:17723029

  7. Hypnosis, memory and amnesia.

    PubMed

    Kihlstrom, J F

    1997-11-29

    Hypnotized subjects respond to suggestions from the hypnotist for imaginative experiences involving alterations in perception and memory. Individual differences in hypnotizability are only weakly related to other forms of suggestibility. Neuropsychological speculations about hypnosis focus on the right hemisphere and/or the frontal lobes. Posthypnotic amnesia refers to subjects' difficulty in remembering, after hypnosis, the events and experiences that transpired while they were hypnotized. Posthypnotic amnesia is not an instance of state-dependent memory, but it does seem to involve a disruption of retrieval processes similar to the functional amnesias observed in clinical dissociative disorders. Implicit memory, however, is largely spared, and may underlie subjects' ability to recognize events that they cannot recall. Hypnotic hypermnesia refers to improved memory for past events. However, such improvements are illusory: hypermnesia suggestions increase false recollection, as well as subjects' confidence in both true and false memories. Hypnotic age regression can be subjectively compelling, but does not involve the ablation of adult memory, or the reinstatement of childlike modes of mental functioning, or the revivification of memory. The clinical and forensic use of hypermnesia and age regression to enhance memory in patients, victims and witnesses (e.g. recovered memory therapy for child sexual abuse) should be discouraged.

  8. New gravitational memories

    NASA Astrophysics Data System (ADS)

    Pasterski, Sabrina; Strominger, Andrew; Zhiboedov, Alexander

    2016-12-01

    The conventional gravitational memory effect is a relative displacement in the position of two detectors induced by radiative energy flux. We find a new type of gravitational `spin memory' in which beams on clockwise and counterclockwise orbits acquire a relative delay induced by radiative angular momentum flux. It has recently been shown that the displacement memory formula is a Fourier transform in time of Weinberg's soft graviton theorem. Here we see that the spin memory formula is a Fourier transform in time of the recently-discovered subleading soft graviton theorem.

  9. Sparse distributed memory overview

    NASA Technical Reports Server (NTRS)

    Raugh, Mike

    1990-01-01

    The Sparse Distributed Memory (SDM) project is investigating the theory and applications of massively parallel computing architecture, called sparse distributed memory, that will support the storage and retrieval of sensory and motor patterns characteristic of autonomous systems. The immediate objectives of the project are centered in studies of the memory itself and in the use of the memory to solve problems in speech, vision, and robotics. Investigation of methods for encoding sensory data is an important part of the research. Examples of NASA missions that may benefit from this work are Space Station, planetary rovers, and solar exploration. Sparse distributed memory offers promising technology for systems that must learn through experience and be capable of adapting to new circumstances, and for operating any large complex system requiring automatic monitoring and control. Sparse distributed memory is a massively parallel architecture motivated by efforts to understand how the human brain works. Sparse distributed memory is an associative memory, able to retrieve information from cues that only partially match patterns stored in the memory. It is able to store long temporal sequences derived from the behavior of a complex system, such as progressive records of the system's sensory data and correlated records of the system's motor controls.

  10. Second Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Second Annual David Derse Memorial Lecture and Award presentation was held on November 12, 2013, at the NCI at Frederick Conference Center to honor David Derse’s outstanding research accomplishments and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career. The Annual David Derse Memorial Lecture and Award is sponsored by the HIV Drug Resistance Program, with support from Hye Kyung Chung-Derse, Ph.D., the National Cancer Institute (NCI), the Foundation for the National Institutes of Health (NIH), and colleagues and friends of Derse who contributed to the memorial fund in his honor.

  11. Second Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Second Annual David Derse Memorial Lecture and Award presentation was held on November 12, 2013, at the NCI at Frederick Conference Center to honor David Derse’s outstanding research accomplishments and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career. The Annual David Derse Memorial Lecture and Award is sponsored by the HIV Drug Resistance Program, with support from Hye Kyung Chung-Derse, Ph.D., the National Cancer Institute (NCI), the Foundation for the National Institutes of Health (NIH), and colleagues and friends of Derse who contributed to the memorial fund in his honor.

  12. [Memory disorders in schizophrenia].

    PubMed

    Danion, J M; Peretti, S; Gras-Vincendon, A; Singer, L

    1992-01-01

    The current interest in memory disorders in schizophrenia results from the way perceptions of schizophrenia--whose organic origin is becoming increasingly evident--and memory--according to which there exist not one, but several memories--have developed. Memory disorders in the schizophrenic cannot be considered in isolation from knowledge accumulated in other areas of the cognitive and neuro-sciences; a more detailed understanding of these disorders requires a comparison of the different cognitive approaches, both with each other and with the neurobiological and clinical approaches, so that they can be integrated. Despite numerous methodological and conceptual difficulties, it now appears to have been established that the schizophrenic's memory deficit should be seen in the context of a wider cognitive deficit, that the memory tasks are not all disturbed and that the memory deficit cannot be identified with one specific form of memory. Thus, iconic formation, short-term memory in the traditionally accepted sense and implicit memory are hardly, if at all, affected; in contrast, the early processing of information, working memory and explicit memory are disturbed, probably to the extent that they require the implementation of strategies to organise the information to be memorized. Finally, in certain tasks, such as those evaluating latent inhibition or negative priming, schizophrenics perform better than normal subjects, suggesting that schizophrenics' cognitive deficit is localised. This profile of memory disorders is compatible with a dysfunction predominating in the frontal and temporo-hippocampal regions. Neuroleptics and anticholinergics have opposite effects on cognitive and mnesic performance, which is improved by the former and aggravated by the latter. The influence of clinical symptoms, positive or negative, institutionalisation of patients and chronic tardive dyskinesia is unclear. Among the theoretical proposals put forward to account for the observed

  13. [Repeated measurement of memory with valenced test items: verbal memory, working memory and autobiographic memory].

    PubMed

    Kuffel, A; Terfehr, K; Uhlmann, C; Schreiner, J; Löwe, B; Spitzer, C; Wingenfeld, K

    2013-07-01

    A large number of questions in clinical and/or experimental neuropsychology require the multiple repetition of memory tests at relatively short intervals. Studies on the impact of the associated exercise and interference effects on the validity of the test results are rare. Moreover, hardly any neuropsychological instruments exist to date to record the memory performance with several parallel versions in which the emotional valence of the test material is also taken into consideration. The aim of the present study was to test whether a working memory test (WST, a digit-span task with neutral or negative distraction stimuli) devised by our workgroup can be used with repeated measurements. This question was also examined in parallel versions of a wordlist learning paradigm and an autobiographical memory test (AMT). Both tests contained stimuli with neutral, positive and negative valence. Twenty-four participants completed the memory testing including the working memory test and three versions of a wordlist and the AMT at intervals of a week apiece (measuring points 1. - 3.). The results reveal consistent performances across the three measuring points in the working and autobiographical memory test. The valence of the stimulus material did not influence the memory performance. In the delayed recall of the wordlist an improvement in memory performance over time was seen. The tests on working memory presented and the parallel versions for the declarative and autobiographical memory constitute informal economic instruments within the scope of the measurement repeatability designs. While the WST and AMT are appropriate for study designs with repeated measurements at relatively short intervals, longer intervals might seem more favourable for the use of wordlist learning paradigms. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Regret as Autobiographical Memory

    ERIC Educational Resources Information Center

    Davison, Ian M.; Feeney, Aidan

    2008-01-01

    We apply an autobiographical memory framework to the study of regret. Focusing on the distinction between regrets for specific and general events we argue that the temporal profile of regret, usually explained in terms of the action-inaction distinction, is predicted by models of autobiographical memory. In two studies involving participants in…

  15. Memory Efficient Ranking.

    ERIC Educational Resources Information Center

    Moffat, Alistair; And Others

    1994-01-01

    Describes an approximate document ranking process that uses a compact array of in-memory, low-precision approximations for document length. Combined with another rule for reducing the memory required by partial similarity accumulators, the approximation heuristic allows the ranking of large document collections using less than one byte of memory…

  16. Memory technology survey

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The current status of semiconductor, magnetic, and optical memory technologies is described. Projections based on these research activities planned for the shot term are presented. Conceptual designs of specific memory buffer pplications employing bipola, CMOS, GaAs, and Magnetic Bubble devices are discussed.

  17. An Exceptional Memory

    ERIC Educational Resources Information Center

    Hunter, Ian M. L.

    1977-01-01

    An account is given of the exceptional memory of the late Professor A. C. Aitken who was also a distinguished mathematician and mental calculator. Compared with Shereshevskii, another man with exceptional memory, he shows the scholar's reliance on conceptual mapping rather than the mnemonist's reliance on perceptual chaining. (Editor)

  18. Eavesdropping without quantum memory

    SciTech Connect

    Bechmann-Pasquinucci, H.

    2006-04-15

    In quantum cryptography the optimal eavesdropping strategy requires that the eavesdropper uses ancillas and quantum memories in order to optimize her information. What happens if the eavesdropper has no quantum memory? It is shown that in this case the eavesdropper obtains a better information/disturbance trade-off by adopting the simple intercept/resend strategy.

  19. Working Memory and Attitudes

    ERIC Educational Resources Information Center

    Jung, Eun Sook; Reid, Norman

    2009-01-01

    Working memory capacity has been shown to be an important factor in controlling understanding in the sciences. Attitudes related to studies in the sciences are also known to be important in relation to success in learning. It might be argued that if working memory capacity is a rate controlling feature of learning and success in understanding…

  20. Human Learning and Memory

    ERIC Educational Resources Information Center

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  1. Human Memory: The Basics

    ERIC Educational Resources Information Center

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  2. Memory Metals (Marchon Eyewear)

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Another commercial application of memory metal technology is found in a "smart" eyeglass frame that remembers its shape and its wearer's fit. A patented "memory encoding process" makes this possible. Heat is not required to return the glasses to shape. A large commercial market is anticipated.

  3. Visual Memory at Birth.

    ERIC Educational Resources Information Center

    Slater, Alan; And Others

    1982-01-01

    Explored new-born babys' capacity for forming visual memories. Used an habituation procedure that accommodated individual differences by allowing each infant to control the time course of habituation trials. Found significant novelty preference, providing strong evidence that recognition memory can be reliably demonstrated from birth. (Author/JAC)

  4. Human Memory: The Basics

    ERIC Educational Resources Information Center

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  5. Human Learning and Memory

    ERIC Educational Resources Information Center

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  6. Reading, Memory, and Metacognition.

    ERIC Educational Resources Information Center

    Byrd, Diana M.; Gholson, Barry

    1985-01-01

    This study was designed to explore relations among reading skills, metareading, memory, and metamemory. Interactions among these skills were investigated as related to reading ability, operativity, and grade level. The effects of experience, operativity, and metacognition on reading and memory skills were discussed. (Author/DWH)

  7. [Learning and memory].

    PubMed

    Lombroso, Paul

    2004-09-01

    Memory is broadly divided into declarative and nondeclarative forms of memory. The hippocampus is required for the formation of declarative memories, while a number of other brain regions including the striatum, amygdala and nucleus accumbens are involved in the formation of nondeclarative memories. The formation of all memories require morphological changes of synapses: new ones must be formed or old ones strengthened. These changes are thought to reflect the underlying cellular basis for persistent memories. Considerable advances have occurred over the last decade in our understanding of the molecular bases of how these memories are formed. A key regulator of synaptic plasticity is a signaling pathway that includes the mitogen activated protein (MAP) kinase. As this pathway is required for normal memory and learning, it is not surprising that mutations in members of this pathway lead to disruptions in learning. Neurofibromatosis, Coffin-Lowry syndrome and Rubinstein-Taybi syndrome are three examples of developmental disorders that have mutations in key components of the MAP kinase signaling pathway.

  8. Predicting Reasoning from Memory

    ERIC Educational Resources Information Center

    Heit, Evan; Hayes, Brett K.

    2011-01-01

    In an effort to assess the relations between reasoning and memory, in 8 experiments, the authors examined how well responses on an inductive reasoning task are predicted from responses on a recognition memory task for the same picture stimuli. Across several experimental manipulations, such as varying study time, presentation frequency, and the…

  9. Experimental Optoelectronic Associative Memory

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin

    1992-01-01

    Optoelectronic associative memory responds to input image by displaying one of M remembered images. Which image to display determined by optoelectronic analog computation of resemblance between input image and each remembered image. Does not rely on precomputation and storage of outer-product synapse matrix. Size of memory needed to store and process images reduced.

  10. Memories of Physical Education

    ERIC Educational Resources Information Center

    Sidwell, Amy M.; Walls, Richard T.

    2014-01-01

    The purpose of this investigation was to explore college students' autobiographical memories of physical education (PE). Questionnaires were distributed to students enrolled in undergraduate Introduction to PE and Introduction to Communications courses. The 261 participants wrote about memories of PE. These students recalled events from Grades…

  11. Regret as Autobiographical Memory

    ERIC Educational Resources Information Center

    Davison, Ian M.; Feeney, Aidan

    2008-01-01

    We apply an autobiographical memory framework to the study of regret. Focusing on the distinction between regrets for specific and general events we argue that the temporal profile of regret, usually explained in terms of the action-inaction distinction, is predicted by models of autobiographical memory. In two studies involving participants in…

  12. Experimental Optoelectronic Associative Memory

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin

    1992-01-01

    Optoelectronic associative memory responds to input image by displaying one of M remembered images. Which image to display determined by optoelectronic analog computation of resemblance between input image and each remembered image. Does not rely on precomputation and storage of outer-product synapse matrix. Size of memory needed to store and process images reduced.

  13. Memory's Role in Catechesis.

    ERIC Educational Resources Information Center

    Williams, Robert Bryan

    The aim of this dissertation is to explicate memory's role in catechesis. Catechesis is a term that early Christians chose to describe their "...work of teaching the gospel and...to mean 'instruction given by word of mouth.'" A brief historical overview confirms the continuity between catechesis and memory from apostolic to present…

  14. Memories of Physical Education

    ERIC Educational Resources Information Center

    Sidwell, Amy M.; Walls, Richard T.

    2014-01-01

    The purpose of this investigation was to explore college students' autobiographical memories of physical education (PE). Questionnaires were distributed to students enrolled in undergraduate Introduction to PE and Introduction to Communications courses. The 261 participants wrote about memories of PE. These students recalled events from Grades…

  15. A Space for Memory

    ERIC Educational Resources Information Center

    Charman, Karen

    2015-01-01

    In this article I examine the possibilities of reparation in an era of privatisation and de-industrialisation. I examine the effect of a recent project Sunshine Memory Space, a space, designed to evoke memories of a de-industrialised urban Melbourne suburb Sunshine. This project offered the opportunity for the effects of industrial change to be…

  16. Distributed multiport memory architecture

    NASA Technical Reports Server (NTRS)

    Kohl, W. H. (Inventor)

    1983-01-01

    A multiport memory architecture is diclosed for each of a plurality of task centers connected to a command and data bus. Each task center, includes a memory and a plurality of devices which request direct memory access as needed. The memory includes an internal data bus and an internal address bus to which the devices are connected, and direct timing and control logic comprised of a 10-state ring counter for allocating memory devices by enabling AND gates connected to the request signal lines of the devices. The outputs of AND gates connected to the same device are combined by OR gates to form an acknowledgement signal that enables the devices to address the memory during the next clock period. The length of the ring counter may be effectively lengthened to any multiple of ten to allow for more direct memory access intervals in one repetitive sequence. One device is a network bus adapter which serially shifts onto the command and data bus, a data word (8 bits plus control and parity bits) during the next ten direct memory access intervals after it has been granted access. The NBA is therefore allocated only one access in every ten intervals, which is a predetermined interval for all centers. The ring counters of all centers are periodically synchronized by DMA SYNC signal to assure that all NBAs be able to function in synchronism for data transfer from one center to another.

  17. Animal models of source memory.

    PubMed

    Crystal, Jonathon D

    2016-01-01

    Source memory is the aspect of episodic memory that encodes the origin (i.e., source) of information acquired in the past. Episodic memory (i.e., our memories for unique personal past events) typically involves source memory because those memories focus on the origin of previous events. Source memory is at work when, for example, someone tells a favorite joke to a person while avoiding retelling the joke to the friend who originally shared the joke. Importantly, source memory permits differentiation of one episodic memory from another because source memory includes features that were present when the different memories were formed. This article reviews recent efforts to develop an animal model of source memory using rats. Experiments are reviewed which suggest that source memory is dissociated from other forms of memory. The review highlights strengths and weaknesses of a number of animal models of episodic memory. Animal models of source memory may be used to probe the biological bases of memory. Moreover, these models can be combined with genetic models of Alzheimer's disease to evaluate pharmacotherapies that ultimately have the potential to improve memory.

  18. Is random access memory random?

    NASA Technical Reports Server (NTRS)

    Denning, P. J.

    1986-01-01

    Most software is contructed on the assumption that the programs and data are stored in random access memory (RAM). Physical limitations on the relative speeds of processor and memory elements lead to a variety of memory organizations that match processor addressing rate with memory service rate. These include interleaved and cached memory. A very high fraction of a processor's address requests can be satified from the cache without reference to the main memory. The cache requests information from main memory in blocks that can be transferred at the full memory speed. Programmers who organize algorithms for locality can realize the highest performance from these computers.