Person: Blaszkowsky, Lawrence
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Blaszkowsky
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Lawrence
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Blaszkowsky, Lawrence
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Publication Pancreatic Ductal Adenocarcinoma(Ovid Technologies (Wolters Kluwer Health), 2013) Konstantinidis, Ioannis T; Warshaw, Andrew; Allen, Jill; Blaszkowsky, Lawrence; Castillo, Carlos; Deshpande, Vikram; Hong, Theodore; Kwak, Eunice Lee; Lauwers, Gregory Y.; Ryan, David; Wargo, Jennifer Ann; Lillemoe, Keith; Ferrone, CristinaObjective: Patients who undergo an R0 resection of their pancreatic ductal adenocarcinoma (PDAC) have an improved survival compared with patients who undergo an R1 resection. It is unclear whether an R1 resection confers a survival benefit over locally advanced (LA) unresectable tumors. Our aim was to compare the survival of patients undergoing an R1 resection with those having LA tumors and to explore the prognostic significance of a 1-mm surgical margin. Methods: Clinicopathologic data from a pancreatic cancer database between January 1993 and July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic disease at exploration. Results: A total of 1705 patients were evaluated for PDAC in the Department of Surgery. Of the 1084 (64%) patients who were surgically explored, 530 (49%) were considered unresectable (286 locally unresectable, 244 with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had an R1 resection. Patients undergoing an R1 resection had a slightly longer survival compared with those who had locally advanced unresectable cancers (14 vs 11 months; P < 0.001). Patients with R0 resections had a favorable survival compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival after resections with 1-mm margin or less (R0-close) were similar to R1 resections: both groups had a significantly shorter median survival than patients with a margin of greater than 1 mm (R0-wide) (16 vs 14 vs 35 months, respectively; P < 0.001). Conclusions: Patients undergoing an R1 resection still have an improved survival compared with patients with locally advanced unresectable pancreatic adenocarcinoma. R0 resections have an improved survival compared with R1 resections, but this survival benefit is lost when the tumor is within 1 mm of the resection margin.Publication The effect of neoadjuvant chemoradiation therapy on the prognostic value of lymph nodes after rectal cancer surgery(Elsevier BV, 2010) Klos, Coen L.; Shellito, Paul; Rattner, David; Hodin, Richard; Cusack, James; Bordeianou, Liliana; Sylla, Patricia; Hong, Theodore; Blaszkowsky, Lawrence; Ryan, Davis P.; Lauwers, Gregory Y.; Chang, Yuchiao; Berger, DavidBackground: Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer. Methods: We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs). Results: A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest. Conclusions: After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis.Publication Yttrium-90 Radioembolization of Hepatic Metastases from Colorectal Cancer(Frontiers Media S.A., 2014) Raval, Mihir; Bande, Dinesh; Pillai, Anil K.; Blaszkowsky, Lawrence; Ganguli, Suvranu; Beg, Muhammad S.; Kalva, Sanjeeva P.Liver metastases from colorectal cancer (CRC) result in substantial morbidity and mortality. The primary treatment is systemic chemotherapy, and in selected patients, surgical resection; however, for patients who are not surgical candidates and/or fail systemic chemotherapy, liver-directed therapies are increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as selective internal radiation therapy (SIRT) or radioembolization, has proven to be effective in terms of extending time to progression of disease and also providing survival benefit. This review focuses on the use of Y-90 microsphere therapy in the treatment of liver metastases from CRC, including a comprehensive review of published clinical trials and prospective studies conducted thus far. We review the methodology, outcomes, and side effects of Y-90 microsphere therapy for metastatic CRC.Publication A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors(Elsevier BV, 2014) Hong, Theodore; Delaney, Thomas; Mamon, Harvey; Willett, Christopher G.; Yeap, Beow; Niemierko, Andrzej; Wolfgang, John; Lu, Hsiao-Ming; Adams, Judith; Weyman, Elizabeth A.; Arellano, Ronald; Blaszkowsky, Lawrence; Allen, Jill; Tanabe, Kenneth; Ryan, David; Zhu, AndrewPurpose To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors. Materials and Methods Fifteen patients were enrolled on a prospective IRB-approved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectablebiopsy-proven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤6 cm. Patients received 15 fractions to a total dose of 45-75 GyE using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring (RPM) based system. Results Of the15 patients enrolled on this clinical trial, 11 had HCC, 3 had ICC, and 1had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients 3 lesions. Toxicities were: Gr 3 bilirubinemia- 2, Gr 3 gastrointestinal bleed- 1, and Gr 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-yr, 2-yr, 3-yr OS is 53%, 40%, and 33% respectively. PFS is 40%,33% and 27% at 1, 2, and 3 years, respectively. Conclusion Respiratory-gated proton beam therapy for liver tumors is feasible. Phase II studies for primary liver tumors and metastatic tumorsare underway.Publication Liquid Versus Tissue Biopsy for Detecting Acquired Resistance and Tumor Heterogeneity in Gastrointestinal Cancers(Springer Science and Business Media LLC, 2019-09) Leshchiner, Ignaty; Elagina, Liudmila; Goyal, Lipika; Siravegna, Giulia; Livitz, Dimitri; Hanna, Megan; Wong, Alicia; Fece de la Cruz, Ferran; Giantonio, Bruce; Roeland, Eric; Ryan, David P.; Aguet, François; Hazar-Rethinam, Mehlika; Dias-Santagata, Dora; Bardelli, Alberto; Parida, Laxmi; Juric, Dejan; Getz, Gad; Corcoran, Ryan B.; Parikh, Aparna; Levovitz, Chaya; Rhrissorrakrai, Kahn; Martin, Elizabeth; Van Seventer, Emily; Slowik, Kara; Ultro, Filippo; Pinto, Christopher; Danysh, Brian; Fetter, Isobel; Shahzade, Heather; Nadres, Brandon; Allen, Jill; Blaszkowsky, Lawrence; Clark, Jeffrey; Murphy, Janet; Nipp, Ryan; Weekes, Colin; Kwan, Eunice; Faris, Jason; Wo, Jennifer; Dey-Guha, Ipsita; Ting, David; Zhu, Andrew; Hong, Theodore; Golub, Todd; Iafrate, John; Adalsteinsson, ViktorDuring cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient1-3. Prior case reports and small case series have suggested that liquid biopsy (specifically, cell-free DNA (cfDNA)) may better capture the heterogeneity of acquired resistance4-8. However, the effectiveness of cfDNA versus standard single-lesion tumor biopsies has not been directly compared in larger scale prospective cohorts of patients following progression on targeted therapy. Here, in a prospective cohort of 42 patients with molecularly-defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of post-progression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically-relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cfDNA, tumor biopsies, and rapid autopsy specimens elucidated substantial geographic and evolutionary differences across lesions. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity, and that the emergence of multiple resistance alterations in an individual patient may represent the “rule” rather than the “exception.” These findings have profound therapeutic implications and highlight the potential advantages of cfDNA over tissue biopsy in the setting of acquired resistance.