Publications by authors named "Stephen Pochebit"

6 Publications

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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

Semiautomated System for Nonurgent, Clinically Significant Pathology Results.

Appl Clin Inform 2018 04 6;9(2):411-421. Epub 2018 Jun 6.

Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

Background: Failure of timely test result follow-up has consequences including delayed diagnosis and treatment, added costs, and potential patient harm. Closed-loop communication is key to ensure clinically significant test results (CSTRs) are acknowledged and acted upon appropriately. A previous implementation of the Alert Notification of Critical Results (ANCR) system to facilitate closed-loop communication of imaging CSTRs yielded improved communication of critical radiology results and enhanced adherence to institutional CSTR policies.

Objective: This article extends the ANCR application to pathology and evaluates its impact on closed-loop communication of new malignancies, a common and important type of pathology CSTR.

Materials And Methods: This Institutional Review Board-approved study was performed at a 150-bed community, academically affiliated hospital. ANCR was adapted for pathology CSTRs. Natural language processing was used on 30,774 pathology reports 13 months pre- and 13 months postintervention, identifying 5,595 reports with malignancies. Electronic health records were reviewed for documented acknowledgment for a random sample of reports. Percent of reports with documented acknowledgment within 15 days assessed institutional policy adherence. Time to acknowledgment was compared pre- versus postintervention and postintervention with and without ANCR alerts. Pathologists were surveyed regarding ANCR use and satisfaction.

Results: Acknowledgment within 15 days was documented for 98 of 107 (91.6%) pre- and 89 of 103 (86.4%) postintervention reports ( = 0.2294). Median time to acknowledgment was 7 days (interquartile range [IQR], 3, 11) preintervention and 6 days (IQR, 2, 10) postintervention ( = 0.5083). Postintervention, median time to acknowledgment was 2 days (IQR, 1, 6) for reports with ANCR alerts versus 6 days (IQR, 2.75, 9) for reports without alerts ( = 0.0351). ANCR alerts were sent on 15 of 103 (15%) postintervention reports. All pathologists reported that the ANCR system positively impacted their workflow; 75% (three-fourths) felt that the ANCR system improved efficiency of communicating CSTRs.

Conclusion: ANCR expansion to facilitate closed-loop communication of pathology CSTRs was favorably perceived and associated with significant improved time to documented acknowledgment for new malignancies. The rate of adherence to institutional policy did not improve.
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http://dx.doi.org/10.1055/s-0038-1654700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996775PMC
April 2018

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

Impact of margin status on local recurrence after mastectomy for ductal carcinoma in situ.

Int J Radiat Oncol Biol Phys 2013 Mar 11;85(4):948-52. Epub 2012 Sep 11.

Harvard Radiation Oncology Program, Boston, MA 02115, USA.

Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy.

Methods And Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy.

Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence.

Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted.
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http://dx.doi.org/10.1016/j.ijrobp.2012.07.2377DOI Listing
March 2013

Surgical margins and the risk of local-regional recurrence after mastectomy without radiation therapy.

Int J Radiat Oncol Biol Phys 2012 Dec 27;84(5):1133-8. Epub 2012 Apr 27.

Harvard Radiation Oncology Program, Boston, Massachusetts, USA.

Purpose: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR.

Methods And Materials: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR.

Results: The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR.

Conclusions: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small.
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http://dx.doi.org/10.1016/j.ijrobp.2012.02.048DOI Listing
December 2012

Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort.

Breast Cancer Res Treat 2012 Jun 4;133(3):1125-30. Epub 2012 Mar 4.

Department of Medical Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue-D1123, Boston, MA 02215, USA.

Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22-46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.
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http://dx.doi.org/10.1007/s10549-012-1993-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709568PMC
June 2012