Publications by authors named "Paul P Koffer"

5 Publications

  • Page 1 of 1

Prostate Cancer Therapeutics and Their Complications: A Primer for the Primary Care Provider.

R I Med J (2013) 2020 Apr 1;103(3):41-45. Epub 2020 Apr 1.

Associate Professor of Medicine, Associate Professor of Surgery, Warren Alpert Medical School of Brown University; Lifespan Cancer Institute, Providence, RI.

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April 2020

New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab.

Clin Breast Cancer 2020 06 19;20(3):246-252. Epub 2019 Dec 19.

Department of Radiation Oncology, Rhode Island Hospital, Providence, RI.

Purpose: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients.

Patients And Methods: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities.

Results: A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040).

Conclusion: New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.
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June 2020

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis.

Int J Radiat Oncol Biol Phys 2017 06 13;98(2):384-391. Epub 2017 Feb 13.

Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.

Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

Methods And Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses.

Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor-positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582).

Conclusions: There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease.
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June 2017

Incidence, Treatment, and Survival Patterns for Sacral Chordoma in the United States, 1974-2011.

Front Oncol 2016 12;6:203. Epub 2016 Sep 12.

Radiation Oncology, Warren Alpert Medical School of Brown University , Providence, RI , USA.

Introduction: Sacral chordomas represent one half of all chordomas, a rare neoplasm of notochordal remnants. Current NCCN guidelines recommend surgical resection with or without adjuvant radiotherapy or definitive radiation for unresectable cases. Recent advances in radiation for chordomas include conformal photon and proton beam radiation. We investigated incidence, treatment, and survival outcomes to observe any trends in response to improvements in surgical and radiation techniques over a near 40-year time period.

Materials And Methods: Three hundred forty-five microscopically confirmed cases of sacral chordoma were identified between 1974 and 2011 from the surveillance, epidemiology, and end results program of the National Cancer Institute. Cases were divided into three cohorts by calendar year, 1974-1989, 1990-1999, and 2000-2011, as well as into two groups by age ≤65 versus >65 to investigate trends over time and age via Chi-square analysis. Kaplan-Meier analyses were performed to determine effects of treatment on survival. Multivariate Cox regression analysis was performed to determine predictors of overall survival (OS).

Results: Five-year OS for the entire cohort was 60.0%. OS correlated significantly with treatment modality, with 44% surviving at 5 years with no treatment, 52% with radiation alone, 82% surgery alone, and 78% surgery and radiation (p < 0.001). Age >65 was significantly associated with non-surgical management with radiation alone or no treatment (p < 0.001). Relatively, fewer patients received radiation between 2000 and 2011 compared to prior time periods (p = 0.03) versus surgery, for which rates which did not vary significantly over time (p = 0.55). However, 5-year OS was not significantly different by time period. Age group and treatment modality were predictive for OS on multivariate analysis (p < 0.001).

Conclusion: Surgery remains an important component in the treatment of sacral chordomas in current practice. Fewer patients were treated with radiation more recently despite advances in photon and proton beam radiation. OS remains unchanged. Additional analyses of margin status, radiation modality, and local control in current practice are warranted.
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September 2016

The Emerging Non-operative Management of Non-metastatic Rectal Cancer: A Population Analysis.

Anticancer Res 2016 Apr;36(4):1699-702

The Warren Alpert School of Medicine, Brown University, Rhode Island Hospital, Providence, RI, U.S.A.

Aim: Recent studies have piloted a nonoperative approach in patients with a complete clinical response to neoadjuvant chemoradiation for non-metastatic rectal cancer. This study evaluated these outcomes in the Surveillance, Epidemiology, and End Results (SEER) database.

Materials And Methods: Using SEER database 8.1.5, we identified patients diagnosed with stage II-III rectal adenocarcinoma between 2004-2011, treated with radiation alone (RT), RT then surgery (RT-S), or surgery then RT (S-RT). Utilization patterns were investigated for all three groups and evaluated using the Chi-squared test. A secondary analysis was limited to current approaches (RT or RT-S). Overall survival (OS) was compared using the log-rank test. Predictors for nonoperative management were compared by multivariable analyses.

Results: From 2004 to 2011, utilization of RT increased from 4% to 8%, RT-S from 57% to 75%, and S-RT decreased from 39% to 18% (p<0.001). In the secondary analysis, predictors for nonoperative management were lower T-stage and N-stage tumors, non-White race, and male sex. With 5,909 evaluable patients at a median follow-up of 35 months, the 5-year OS in the RT group was 56% vs. 80% in the RT-S group (log-rank p<0.001).

Conclusion: Nonoperative management of rectal cancer is increasing despite an apparent detriment in OS compared to a combined modality approach, that may reflect a selection bias in the SEER database.
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April 2016