Memorial Sloan Kettering Cancer Center
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ABSTRACT:
PROVIDER: EGAO00000000901 | EGA |
REPOSITORIES: EGA
Publications
Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer.
Makohon-Moore Alvin P AP Zhang Ming M Reiter Johannes G JG Bozic Ivana I Allen Benjamin B Kundu Deepanjan D Chatterjee Krishnendu K Wong Fay F Jiao Yuchen Y Kohutek Zachary A ZA Hong Jungeui J Attiyeh Marc M Javier Breanna B Wood Laura D LD Hruban Ralph H RH Nowak Martin A MA Papadopoulos Nickolas N Kinzler Kenneth W KW Vogelstein Bert B Iacobuzio-Donahue Christine A CA
Nature genetics 20170116 3
The extent of heterogeneity among driver gene mutations present in naturally occurring metastases-that is, treatment-naive metastatic disease-is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, ac ...[more]
Similar Datasets
Project description:The Memorial Sloan Kettering Cancer Center (MSKCC) recommendations on prostate cancer screening were developed in response to three limitations of previous screening guidelines: insufficient evidence base, failure to link screening with treatment, and lack of risk stratification. The objective of the recommendations is to provide a schema for prostate cancer screening that maximizes the benefits, in terms of reduction in prostate cancer-specific mortality, and minimizes the harms, in terms of overdiagnosis and overtreatment. We recommend the following schema for men choosing to be screened following informed decision-making: starting at age 45, prostate-specific antigen (PSA) without digital rectal examination. If PSA ≥ 3 ng/mL: consider prostate biopsy; if PSA ≥ 1 but < 3 ng/mL: return for PSA testing every 2-4 years; if PSA < 1 ng/mL: return for PSA testing at 6-10 years. PSA testing should end at age 60 for men with PSA ≤ 1 ng/ mL; at 70, unless a man is very healthy and has a higher than average PSA; at 75 for all men. The decision to biopsy a man with a PSA > 3 ng/mL should be based on a variety of factors including repeat blood draw for confirmatory testing of the PSA level, digital rectal examination results, and workup for benign disease. Additional reflex tests in blood such as a free-to-total PSA ratio, the Prostate Health Index, or 4Kscore, or urinary testing of PCA3, can also be informative in some patients. The best evidence suggests that more restricted indication for prostate biopsy and a more focused approach to pursue screening in men at highest risk of lethal cancer would retain most of the mortality benefits of aggressive screening schema, while importantly reducing harms from overdetection and overtreatment.
| S-EPMC4842100 | biostudies-literature
Project description:BackgroundThe proliferation of relationships between community health systems and academic medical centers has created a need to identify effective components of these models. This article reports on frontline physician experiences, with one such relationship established through the Memorial Sloan Kettering Cancer Center (MSK) Cancer Alliance. MSK created the Alliance with the goals of rapidly bringing the newest standards of care into community settings and increasing patient access to clinical trials in their local communities.MethodsAlliance leadership administered a 10-question anonymous survey to physicians treating patients with cancer across the 3 Alliance member health systems: Hartford HealthCare Cancer Institute, Lehigh Valley Cancer Institute, and Miami Cancer Institute at Baptist Health South Florida. The purpose of the survey was to identify opportunities to improve physician engagement.ResultsThere were 103 clinician respondents across Alliance members, of which 87 reported participation in a disease management team and were included in the final analysis. Most respondents reported high value from Alliance activities, such as attending MSK tumor boards (94%) and lecture series (96%), among those who reported them applicable. Across all respondents, most reported satisfaction with engagement opportunities, such as MSK physician participation in their institution's meetings (76%). When asked where they would like to see increased engagement, the most commonly reported response was for more lecture series (45%). Most respondents (88%) reported that the Alliance led to practice change, either for themselves or for other clinicians at their institution. Many attributed this practice change to MSK disease-specific process measures.ConclusionsThe activities most valued by community physicians were heavily physician relationship-based. The encouraging experience of the MSK Cancer Alliance suggests that activities involving physician investment may be effective for promoting practice change in the context of cross-institution relationships. Future research is needed in this area.
| S-EPMC7513935 | biostudies-literature
Project description:BackgroundLow-molecular-weight heparin has been the preferred treatment of cancer-associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs).ObjectivesThe Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT.MethodsFrom January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway.ResultsThe 6-month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%-5.7%) and 2.2% (95% CI, 1.1%-3.2%), respectively. The incidence of clinically relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI, 3.7%-7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6-month cumulative mortality rate was 22.2% (95% CI, 19.4%-24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years.ConclusionOur institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.
| S-EPMC6611365 | biostudies-literature
Project description:BackgroundExtraneural metastasis of glioma is a rare event, often occurring in patients with advanced disease. Genomic alterations associated with extraneural glioma metastasis remain incompletely understood.MethodsTen patients at Memorial Sloan Kettering Cancer Center diagnosed with extraneural metastases of glioblastoma (9 patients) and gliosarcoma (1 patient) from 2003 to 2018 were included in our analysis. Patient characteristics, clinical course, and genomic alterations were evaluated.ResultsPatient age at diagnosis ranged from 14 to 73, with 7 men and 3 women in this group. The median overall survival from initial diagnosis and from diagnosis of extraneural metastasis was 19.6 months (range 11.2 to 57.5 months) and 5 months (range 1 to 16.1 months), respectively. The most common site of extraneural metastasis was bone, with other sites being lymph nodes, dura, liver, lung, and soft tissues. All patients received surgical resection and radiation, and 9 patients received temozolomide, with subsequent chemotherapy appropriate for individual cases. 1 patient had an Ommaya and then ventriculoperitoneal shunt placed, and 1 patient underwent craniectomy for cerebral edema associated with a brain abscess at the initial site of resection. Genomic analysis of primary tumors and metastatic sites revealed shared and private mutations with a preponderance of tumor suppressor gene alterations, illustrating clonal evolution in extraneural metastases.ConclusionsSeveral risk factors emerged for extraneural metastasis of glioblastoma and gliosarcoma, including sarcomatous dedifferentiation, disruption of normal anatomic barriers during surgical resection, and tumor suppressor gene alterations. Next steps with this work include validation of these genomic markers of glioblastoma metastases in larger patient populations and the development of preclinical models. This work will lead to a better understanding of the molecular mechanisms of metastasis to develop targeted treatments for these patients.
| S-EPMC8153825 | biostudies-literature
Project description:PurposeWe report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance at a tertiary cancer center.Materials and methodsA total of 2,907 patients were managed with active surveillance between 2000 and 2017, of whom 2,664 had Grade Group 1 disease. Patients were recommended confirmatory biopsy to verify eligibility and were followed semiannually with prostate specific antigen, digital rectal examination and review of symptoms. Magnetic resonance imaging was increasingly used in recent years. Biopsy was repeated every 2 to 3 years or after a sustained prostate specific antigen increase or changes in magnetic resonance imaging/digital rectal examination. The Kaplan-Meier method was used to estimate probabilities of treatment, progression and development of metastasis.ResultsMedian patient age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer the treatment-free probability at 5, 10 and 15 years was 76% (95% CI 74-78), 64% (95% CI 61-68) and 58% (95% CI 51-64), respectively. At 5, 10 and 15 years there were 1,146, 220 and 25 men at risk for metastasis, respectively. Median followup for those without metastasis was 4.3 years (95% CI 2.3-6.9). Distant metastasis developed in 5 men. Upon case note review only 2 of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2-2.0) at 10 years.ConclusionsActive surveillance is a safe strategy over longer followup for appropriately selected patients with Grade Group 1 disease following a well-defined monitoring plan.
| S-EPMC7480884 | biostudies-literature
Project description:We report the pathology and outcome of secondary skull base tumors in patients previously treated with external beam radiation for retinoblastoma (Rb). Rb patients are at increased risk of second head and neck primary malignancies due to early radiation exposure during treatment and loss of RB1 protein in genetic carriers. An institutional database was reviewed for patients with retinoblastoma who had previously received radiation therapy and subsequently developed skull base tumors. Seventeen patients met the selection criteria. The median age of Rb diagnosis was 12 months. Thirteen cases underwent enucleation in addition to radiation therapy as part of initial Rb treatment. A median of 19 years elapsed between the diagnosis of Rb and diagnosis of skull base malignancy. The most common tumors were osteogenic sarcoma (39%) and leiomyosarcoma (22%). Eleven (71%) patients received postoperative chemotherapy, and 7 (41%) received postoperative radiotherapy. Three (24%) patients underwent salvage surgery for recurrent disease. Five-year survival was 68%, and 10-year survival was 51% by Kaplan-Meier analysis. Secondary malignancy in Rb patients is a well-defined event. The use of surgery with appropriate adjuvant therapy was associated with a 51% 10-year survival in this study population.
| S-EPMC3312595 | biostudies-other
Project description:Prostate-specific antigen (PSA) density is an established prognostic marker for prostate cancer. We investigated whether the inclusion of PSA density or prostate volume in the Memorial Sloan Kettering Cancer Center nomograms improves the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Among the 11 725 men included, 2140 developed BCR. Neither PSA density nor prostate volume was associated with BCR when added to either the pre-RP or post-RP model (all p values ≥0.10) and changes in the C index were very small (largest change, 0.002). The results were robust to exclusion of outlying prostate volumes and restriction to patients treated after 2005. There is no justification for adding prostate volume or PSA density to BCR nomograms.Patient summaryAddition of prostate volume or prostate-specific antigen density to Memorial Sloan Kettering Cancer Center prediction schemes did not improve the prediction of recurrence of prostate cancer after removal of the prostate.
| S-EPMC8317781 | biostudies-literature
Project description:Organisation EGAO00000001044
| EGAO00000001044 | EGA
Project description:We report the application of Chromosome Conformation Capture Carbon-copy (5C) to a 4.5 Mb stretch of the mouse X chromosome encompassing the X inactivation center locus. We uncover a series of discrete 200kb-1Mb topologically associating domains (TADs). These align with several domain-wide epigenomic features as well as co-regulated gene clusters. 5C analysis in EED and G9A mutants reveal that this segmental organisation in TADs does not relie on the underlying H3K27me3 or H3K9me2 blocks. Deletion of a boundary between two TADs leads to ectopic chromosomal contacts between them. Analysis of mESCs, mNPCs and MEFs suggest that the positioning of TADs on the chromosome is stable during cell differentiation though their internal organisation changes. Comparison of male (XY) and female (XX) differentiated cells highlights that the long-range chromosomal contacts within TADs are dampened on the inactive X compared to the active X. 5C oligonucleotides were designed around HindIII restriction site following an alternative scheme
2012-04-11 | E-GEOD-35721 | biostudies-arrayexpress