Publications by authors named "Kelsey Natsuhara"

5 Publications

  • Page 1 of 1

Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer.

Ann Surg Oncol 2019 Oct 21;26(11):3502-3509. Epub 2019 Jun 21.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Background: The prognostic significance of low-volume residual nodal disease following neoadjuvant chemotherapy (NAC) is unknown.

Methods: Women with cT1-4N0-1 breast cancer treated with NAC were identified from Dana-Farber/Brigham and Women's Cancer Center (DFBWCC) and the National Cancer Database (NCDB). Disease-free survival (DFS) and overall survival (OS) estimates according to pathologic nodal status were calculated using the Kaplan-Meier method, with Cox proportional hazards regression used to assess the effect of clinical variables on survival outcomes.

Results: Among 967 DFBWCC patients, 27 (2.8%) had residual isolated tumor cells (ITCs) and 61 (6.3%) had micrometastases. Five-year DFS was significantly worse in those with residual ITCs (73.5%) and micrometastases (74.7%) relative to those who were ypN0 following NAC (88.4%, p < 0.001). On adjusted analysis, those with residual ITCs (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.20-3.81) and micrometastases (HR 2.14, 95% CI 1.20-3.81) had increased risk of recurrence relative to ypN0 patients. Among 35,536 NCDB patients, 543 (1.5%) had ITCs and 1132 (3.2%) had micrometastases. Five-year OS estimates were significantly worse with increasing residual nodal burden: ypN0, 88.9%; ypN0[i+], 82.8%; ypN1mi, 79.5%; ypN1, 77.6% (p < 0.001). Compared with patients with ypN0 disease, NCDB patients with ITCs and micrometastases had 1.9- and 2.2-fold risk of death (p < 0.001). On subgroup analysis, the effect of low-volume residual disease on mortality was most pronounced in patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive disease.

Conclusions: Low-volume residual nodal disease following NAC is associated with poorer DFS and OS relative to those who are node negative.
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http://dx.doi.org/10.1245/s10434-019-07517-2DOI Listing
October 2019

Impact of Genomic Assay Testing and Clinical Factors on Chemotherapy Use After Implementation of Standardized Testing Criteria.

Oncologist 2019 05 3;24(5):595-602. Epub 2018 Aug 3.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Background: For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention.

Materials And Methods: We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing.

Results: The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt.

Conclusion: Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation.

Implications For Practice: This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays.
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http://dx.doi.org/10.1634/theoncologist.2018-0154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516114PMC
May 2019

Nurse-midwives' ability to diagnose acute third- and fourth-degree obstetric lacerations in western Kenya.

BMC Pregnancy Childbirth 2017 Sep 18;17(1):308. Epub 2017 Sep 18.

Division of Global Health and Human Rights, Department of Emergency Medicine, Massachusetts General Hospital, 125 Nashua Street, Suite 910, Boston, MA, 02114, USA.

Background: Obstetric fistula devastates the lives of women and is found most commonly among the poor in resource-limited settings. Unrepaired third- and fourth-degree perineal lacerations have been shown to be the source of approximately one-third of the fistula burden in fistula camps in Kenya. In this study, we assessed potential barriers to accurate identification by Kenyan nurse-midwives of these complex perineal lacerations in postpartum women.

Methods: Nurse-midwife trainers from each of the seven sub-counties of Siaya County, Kenya were assessed in their ability to accurately identify obstetric lacerations and anatomical structures of the perineum, using a pictorial assessment tool. Referral pathways, follow-up mechanisms, and barriers to assessing obstetric lacerations were evaluated.

Results: Twenty-two nurse-midwife trainers were assessed. Four of the 22 (18.2%) reported ever receiving formal training on evaluating third- and fourth-degree obstetric lacerations, and 20 of 22 (91%) reported health-system challenges to adequately completing their examination of the perineum at delivery. Twenty-one percent of third- and fourth-degree obstetric lacerations in the pictorial assessment were incorrectly identified as first- or second-degree lacerations.

Conclusion: County nurse-midwife trainers in Siaya, Kenya, experience inadequate training, equipment, staffing, time, and knowledge as barriers to adequate diagnosis and repair of third- and fourth-degree perineal tears.
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http://dx.doi.org/10.1186/s12884-017-1484-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604156PMC
September 2017

Implementation of Surgeon-Initiated Gene Expression Profile Testing (Onco type DX) Among Patients With Early-Stage Breast Cancer to Reduce Delays in Chemotherapy Initiation.

J Oncol Pract 2017 09 31;13(9):e815-e820. Epub 2017 Aug 31.

Dana-Farber Cancer Institute; Dana-Farber/Brigham and Women's Cancer Center; Brigham and Women's Hospital; and Harvard Medical School, Boston, MA.

Purpose: Delays to adjuvant chemotherapy initiation in breast cancer may adversely affect clinical outcomes and patient satisfaction. We previously identified an association between genomic testing (Onco type DX) and delayed chemotherapy initiation. We sought to reduce the interval between surgery and adjuvant chemotherapy initiation by developing standardized criteria and workflows for Onco type DX testing.

Methods: Criteria for surgeon-initiated reflex Onco type DX testing, workflows for communication between surgeons and medical oncologists, and a streamlined process for receiving and processing Onco type DX requests in pathology were established by multidisciplinary consensus. Criteria for surgeon-initiated testing included patients ≤ 65 years old with T1cN0 (grade 2 or 3), T2N0 (grade 1 or 2), or T1/T2N1 (grade 1 or 2) breast cancer on final surgical pathology. Medical oncologists could elect to initiate Onco type testing for cases falling outside the criteria. We then examined 720 consecutive patients with breast cancer who underwent Onco type DX testing postoperatively between January 1, 2014 and November 28, 2016 and measured intervals between date of surgery, Onco type DX order date, result received date, and chemotherapy initiation date (if applicable) before and after intervention implementation.

Results: The introduction of standardized criteria and workflows reduced time between surgery and Onco type DX ordering, and time from surgery to receipt of result, by 7.3 days ( P < .001) and 6.3 days ( P < .001), respectively. The mean number of days between surgery and initiation of chemotherapy was also reduced by 6.4 days ( P = .004).

Conclusion: Developing consensus on Onco type DX testing criteria and implementing streamlined workflows has led to clinically significant reductions in wait times to chemotherapy decision making and initiation.
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http://dx.doi.org/10.1200/JOP.2017.023788DOI Listing
September 2017

Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization.

Stem Cell Reports 2017 05 13;8(5):1226-1241. Epub 2017 Apr 13.

Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Sciences, 3 Blackfan Circle, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address:

Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling. In contrast, Mmp9 was dispensable for HSPC budding, being instead required for proper colonization of secondary niches. Significantly, these migration defects were mimicked by overexpression and blocked by knockdown of C-X-C motif chemokine-12 (cxcl12), suggesting that Mmp9 controls CHT homeostasis through chemokine regulation. Our findings indicate Mmp2 and Mmp9 play distinct but complementary roles in developmental HSPC production and migration.
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http://dx.doi.org/10.1016/j.stemcr.2017.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425629PMC
May 2017