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Michael Vouche,
Laura Kulik,
Rohiatassi,
Khairuddin Memon,
Ryan Hickey,
Daniel Ganger,
Frank H Miller,
Vahidyaghmai,
Michael Abecassis,
Talia Baker, Mary Mulcahy,
Ritu Nayar,
Robert J Lewandowski,
Riad Salem
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ABSTRACT: AIM: To compare radiological and pathological changes and test the adjunct efficacy of Sorafenib to Y90 as a bridge to transplantation in HCC. METHODS: 15 patients with 16 HCC lesions randomized to Y90 without (Group A, n=9) or with Sorafenib (Group B, n=7). Size (WHO, RECIST), enhancement (EASL, mRECIST) and diffusion-weighted imagingcriteria (ADC) measurements were obtained at baseline, 1 and every 3 months after treatment until transplantation.Percentage necrosisin explanted tumors was correlated with imaging findings. RESULTS: 100%, 50-99% and <50% pathological necrosis was observed in 6 (67%), 1 (11%) and 2 (22%) tumors in Group A and 3 (42%), 2 (28%) and 2 (28%) in Group B, respectively (p=0.81).While ADC (p=0.46) did not change after treatment, WHO (p=0.06) and RECIST (p=0.08) response at 1 month failed to reach significance,but significant responses by EASL (p<0.01/0.03) and mRECIST(p<0.01/0.03)at 1 and 3 months were observed. Response was equivalent by EASL or mRECIST.No difference in response rates were observed between groups A and B at 1 and 3 months by WHO, RECIST, EASL, mRECIST or ADC measurements. Despite failing to reach significance, smaller baseline size was associated with CPN(RECIST: p=0.07; WHO: p=0.05).However, a cut-off size of 35mm was predictive of CPN (p=0.005). CPN could not be predicted by WHO (p=0.25 and 0.62), RECIST (p=0.35 and 0.54), EASL (p=0.49 and 0.46), mRECIST (p=0.49 and 0.60) or ADC (p=0.86 and 0.93). CONCLUSION: The adjunct of Sorafenib did not augment radiological or pathological response to Y90 therapy for HCC.Equivalent significant reduction in enhancementat 1 and 3 months by EASL/mRECIST were noted.Neither EASL nor mRECIST could reliably predict CPN. (HEPATOLOGY 2013.).
Hepatology 05/2013; · 11.66 Impact Factor
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ABSTRACT: Introduction: The multikinase inhibitors sorafenib (SO) and sunitinib (SU) have shown benefit in a wide range of solid tumors. Although these agents are generally well tolerated, they may be associated with dermatologic adverse events, particularly hand-foot skin reaction (HFSR). The aim of this study is to evaluate the impact of HFSR associated with these multikinase inhibitors on patient health-related quality of life (HRQOL). Methods: Twenty-three patients with HFSR related to SO or SU were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 for clinical severity and for impact on HRQOL through completion of the patient self-administered Skindex-16 (SK-16). Clinical severity scores were compared to HRQOL assessments. Results: Of the 23 patients with HFSR, clinical severity was grade 1 in 17.4%, grade 2 in 74%, and grade 3 in 8.6%. Median SK-16 scores were reported for symptoms (53.3), emotions (30.6), and functioning subscales (33.3). Median symptoms and emotions scores positively correlated with HFSR clinical severity grade. Conclusions: These findings demonstrate that HFSR related to SO or SU negatively impacts HRQOL, with the symptoms domain being most significantly affected. In addition, CTCAE toxicity grading correlates with HRQOL. J Drugs Dermatol. 2012;11(11)e61-e65.
Journal of drugs in dermatology: JDD 11/2012; 11(11):e61-5. · 1.57 Impact Factor
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Kent Sato,
Robert J Lewandowski,
James T Bui,
Reed Omary,
Russell D Hunter,
Laura Kulik, Mary Mulcahy,
David Liu,
Howard Chrisman,
Scott Resnick,
Albert A Nemcek,
Robert Vogelzang,
Riad Salem
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ABSTRACT: In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.
CardioVascular and Interventional Radiology 04/2012; 29(4):522-9. · 2.09 Impact Factor
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ABSTRACT: To investigate the change in creatinine clearance (CrCl) over time following upper abdominal radiation utilizing a dose-volume histogram (DVH) multivariate analysis.
The study population included 125 patients with gastrointestinal malignancy treated with abdominal radiation therapy at our institution between 1994 and 2006, with available creatinine and DVH information. Kidney dose-volume data collected included mean kidney dose, volume of kidney irradiated, V5, V10, and V20 of total kidney volume, and number of mL of kidney greater than and less than 20 Gy.
With a median follow-up of 2.4 years, and a mean kidney dose of 16.2 Gy, a significant correlation between decrease in CrCl and irradiated kidney volume observed was noted for all DVH parameters. The strongest correlations were found when using V5, V10, and number of mL of kidney treated to greater than 20 Gy. There was no significant change in number of antihypertensive medications taken by patients over time, and no relationship between outcome variables and pre-existing comorbidities.
This is the first study that we are aware of comparing DVH data with measurement of renal toxicity. We show significant correlations between dose and volume irradiated and decline in renal function. This will be clinically useful when determining a treatment plan for patients with borderline preradiation CrCl and provides evidence that minimizing radiation to the kidney could have important clinical ramifications.
American journal of clinical oncology 03/2010; 34(1):53-7. · 2.21 Impact Factor
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Ahsun Riaz,
Robert J Lewandowski,
Laura Kulik,
Robert K Ryu, Mary F Mulcahy,
Talia Baker,
Vanessa Gates,
Ritu Nayar,
Ed Wang,
Frank H Miller,
Kent T Sato,
Reed A Omary,
Michael Abecassis,
Riad Salem
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ABSTRACT: To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre- and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa (κ) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have ≥85% specificity for predicting complete pathologic necrosis. The κ coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.
CardioVascular and Interventional Radiology 12/2009; 33(6):1143-52. · 2.09 Impact Factor
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ABSTRACT: Infectious complications after yttrium-90 (y-90) radioembolization of hepatic tumors are rare. Most reports describe hepatic abscesses as complications of other locoregional therapies, such as transcatheter arterial embolization or chemoembolization. These usually occur in patients with a history of biliary intervention and present several weeks after treatment. We report a case of hepatic abscess formed immediately after y-90 radioembolization of a hepatic metastasis in a patient who had no history of previous biliary instrumentation.
CardioVascular and Interventional Radiology 09/2009; 33(3):650-3. · 2.09 Impact Factor
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ABSTRACT: Response Evaluation Criteria in Solid Tumors (RECIST) guidelines assume spherical shape of tumors. Morphology of pancreatic adenocarcinoma (PAC) on multidetector row computed tomography was investigated to evaluate the applicability of RECIST guidelines.
Study population comprised 16 patients with histologically confirmed localized PAC enrolled in a phase II clinical trial of chemoradiation. Pancreatic adenocarcinomas were segmented on baseline and follow-up multidetector row computed tomography with commercially available software. Tumor volumes (mL), RECIST diameter (mm), volume equivalent sphere diameter (VESD, mm), maximum 3-dimensional diameter (M3DD, mm), and elongation value were obtained. RECIST diameter, VESD and M3DD of the tumors at baseline and follow-up were compared to determine differences. Elongation values were analyzed. The significance level was set at P less than 0.05.
Mean volume, RECIST diameter, VESD, M3DD, and elongation for baseline versus follow-up studies were 23.12 mL versus 19.43 mL (P > 0.05), 41.86 mm versus 39.35 mm (P > 0.05), 33.14 mm versus 32.1 mm (P > 0.05), 51.76 mm versus 51.73 mm (P > 0.05), and 0.67 versus 0.76 (P > 0.05), respectively. There was a significant difference at baseline and follow-up between RECIST diameter, VESD, and M3DD (P < 0.05, in all instances).
Our results suggest that PACs are not spherical in shape. Evaluation of PAC treatment response based on RECIST guidelines may not be accurate.
Pancreas 07/2009; 38(7):799-803. · 2.39 Impact Factor
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Ron C Gaba,
Robert J Lewandowski,
Laura M Kulik,
Ahsun Riaz,
Saad M Ibrahim, Mary F Mulcahy,
Robert K Ryu,
Kent T Sato,
Vanessa Gates,
Michael M Abecassis,
Reed A Omary,
Talia B Baker,
Riad Salem
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ABSTRACT: To describe volumetric changes of "radiation lobectomy," a manifestation of hepatic parenchymal response to lobar (90)Y microsphere radioembolization.
Twenty patients exhibiting this phenomenon were identified. Pre- and posttreatment absolute right and left hepatic lobar volume (HLV), relative HLV (rHLV = HLV/total liver volume), and degree of lobar atrophy (DA) or hypertrophy (DH) (DA or DH = |posttreatment rHLV - pretreatment rHLV|) were determined. Laboratory toxicities, tumor response, and patient survival were also assessed.
Twenty patients with primary (HCC, n = 17; peripheral cholangiocarcinoma, n = 3) liver malignancies demonstrated findings of radiation lobectomy. Initial absolute right and left HLV was 955 cm(3) (range 644-1,842 cm(3), rHLV = 57%) and 719 cm(3) (range 328-1,387 cm(3), rHLV = 43%), respectively. Following (90)Y, absolute right HLV decreased to 460 cm(3) (range 185-948 cm(3), 52% reduction, rHLV = 31%, DA = 26%, P < 0.0001), while absolute left HLV increased to 1,004 cm(3) (range 560-1,558 cm(3), 40% increase, rHLV = 69%, DH = 26%, P < 0.0001). No grade 3 or 4 bilirubin toxicities were encountered. Tumor response ranged from 55% to 70% by size criteria. Forty-six percent 5-year survival was achieved in HCC patients.
Radiation lobectomy following (90)Y radioembolization of right lobe tumors manifests extensive contralateral lobar hypertrophy, high response rates, and prolonged survival. This phenomenon was noted in 6.4% (20/315) of the entire cohort and 19.8% (20/101) of patients with unilobar right lobe tumors. Further investigation is necessary to determine contributing factors that may predict this effect.
Annals of Surgical Oncology 05/2009; 16(6):1587-96. · 4.17 Impact Factor
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Saad M Ibrahim,
Paul Nikolaidis,
Frank H Miller,
Robert J Lewandowski,
Robert K Ryu,
Kent T Sato,
Sean Senthilnathan,
Ahsun Riaz,
Laura Kulik, Mary F Mulcahy,
Reed A Omary,
Riad Salem
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ABSTRACT: A therapy gaining rapid clinical adoption involves radioembolization with the use of Yttrium-90 (90Y) microspheres. The 20-60 microm-sized microspheres are injected trans-arterially and flow to hepatic tumors given their preferential blood supply from the hepatic artery. Once they lodge in the arterioles, they impart a very intense local radiotherapeutic effect. Given the combined radiation and embolic effect, the imaging findings imparted by this mode of action differ significantly from other treatments. This work represents a comprehensive review of the imaging findings following radioembolization in patients with primary liver tumors. The report discusses imaging response, benign secondary effects, and complications. This should help educate the radiologist on imaging findings that should be expected following radioembolization and therefore aid in the proper image interpretation.
Abdominal Imaging 10/2008; 34(5):566-81. · 1.73 Impact Factor
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ABSTRACT: The purpose of our study was to determine if preferential radiographic tumor response occurs in tumors located in posterior versus anterior liver segments following radioembolization with yttrium-90 glass microspheres. One hundred thirty-seven patients with chemorefractory liver metastases of various primaries were treated with yttrium-90 glass microspheres. Of these, a subset analysis was performed on 89 patients who underwent 101 whole-right-lobe infusions to liver segments V, VI, VII, and VIII. Pre- and posttreatment imaging included either triphasic contrast material-enhanced CT or gadolinium-enhanced MRI. Responses to treatment were compared in anterior versus posterior right lobe lesions using both RECIST and WHO criteria. Statistical comparative studies were conducted in 42 patients with both anterior and posterior segment lesions using the paired-sample t-test. Pearson correlation was used to determine the relationship between pretreatment tumor size and posttreatment tumor response. Median administered activity, delivered radiation dose, and treatment volume were 2.3 GBq, 118.2 Gy, and 1,072 cm(3), respectively. Differences between the pretreatment tumor size of anterior and posterior liver segments were not statistically significant (p = 0.7981). Differences in tumor response between anterior and posterior liver segments were not statistically significant using WHO criteria (p = 0.8557). A statistically significant correlation did not exist between pretreatment tumor size and posttreatment tumor response (r = 0.0554, p = 0.4434). On imaging follow-up using WHO criteria, for anterior and posterior regions of the liver, (1) response rates were 50% (PR = 50%) and 45% (CR = 9%, PR = 36%), and (2) mean changes in tumor size were -41% and -40%. In conclusion, this study did not find evidence of preferential radiographic tumor response in posterior versus anterior liver segments treated with yttrium-90 glass microspheres.
CardioVascular and Interventional Radiology 06/2008; 31(6):1124-32. · 2.09 Impact Factor
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Robert J Lewandowski,
Joshua Tepper,
Dingxin Wang,
Saad Ibrahim,
Frank H Miller,
Laura Kulik, Mary Mulcahy,
Robert K Ryu,
Kent Sato,
Andrew C Larson,
Riad Salem,
Reed A Omary
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ABSTRACT: To evaluate the combined use of transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging and dynamic contrast-enhanced MR imaging to determine complete tumor targeting during transcatheter arterial chemoembolization (TACE) when performed within an integrated MR imaging-interventional radiology (IR) angiography suite.
Between October 2006 and March 2007, eight consecutive patients with unresectable hepatocellular carcinoma (HCC) successfully underwent TACE in a combined MR imaging-IR suite. All patients were male, with a mean age of 59 years (range, 41-71 years). Tumor enhancement on TRIP MR images before and after TACE were qualitatively compared with dynamic contrast-enhanced MR images obtained after TACE. The authors computed the prevalence of perfusion mismatch. The presence of a perfusion mismatch was judged in a binary fashion.
A perfusion match, confirming complete tumor targeting, occurred in six of the eight patients (75%). There was a perfusion mismatch in two patients (25%). Subsequent interrogation showed that the underlying cause of the mismatch was secondary to an unexpected collateral vessel in the first patient and watershed location of the tumor in the second patient.
Performing TACE in an MR imaging-IR suite can facilitate complete tumor targeting. By comparing perfusion images from TRIP and contrast-enhanced MR sequences, the operator gains confidence and can potentially obtain more selective catheter placement during TACE.
Journal of Vascular and Interventional Radiology 06/2008; 19(5):698-705. · 2.08 Impact Factor
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Kent Sato,
Robert J Lewandowski,
James Bui,
Reed Omary,
Russell Hunter,
Laura Kulik, Mary Mulcahy,
David Liu,
Howard Chrisman,
Scott Resnick,
Albert Nemcek,
Robert Vogelzang,
Riad Salem
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[hide abstract]
ABSTRACT: In Canada and Europe, yttrium-90 microspheres (TheraSphere((R)); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.
CardioVascular and Interventional Radiology 05/2006; · 2.09 Impact Factor
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Thomas K Rhee,
Reed A Omary,
Vanessa Gates,
Taofic Mounajjed,
Andrew C Larson,
Omar Barakat,
Kent T Sato, Mary Mulcahy,
Stuart Gordon,
Robert J Lewandowski,
Riad Salem
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ABSTRACT: Yttrium 90 radioembolization is a transcatheter therapy for unresectable hepatocellular carcinoma (HCC) that delivers internal radiation to tumors. In contrast to the usual method of lobar regional delivery, catheter-directed computed tomographic (CT) angiography was investigated as a potentially useful technique to evaluate the administration of segmental 90Y tumor radiation doses superselectively without significantly altering liver function or Child-Pugh classification.
Fourteen patients underwent 90Y therapy for unresectable HCC. After standard angiographic placement of a 3-F microcatheter in a segmental hepatic artery supplying the tumor, each patient underwent CT angiography with use of segmental hepatic artery injection of iodinated contrast agent to confirm segmental perfusion and delineate segmental liver volume. 90Y was later injected into the same segmental artery. Target dose was calculated according to infused 90Y activity and targeted hepatic volume with standard lobar volume (before CT angiography) versus segmental liver volume (after CT angiography). The Wilcoxon signed-rank test (alpha = 0.05) was used to compare the estimated 90Y dose before CT angiography with the actual 90Y dose after CT angiography, as well as changes in serum bilirubin level and Child-Pugh classification as a result of treatment.
The mean estimated tumor dose before CT angiography (SD) was 100 Gy +/- 43 (range, 35-169 Gy). The mean actual tumor dose after CT angiography was 348 Gy +/- 204 (range, 105-857 Gy), which was significantly greater (P < .001). The mean bilirubin level before treatment was 1.0 mg/dL +/- 0.97 (range, 0.2-4.0 mg/dL), whereas the mean bilirubin level after treatment was 1.3 mg/dL +/- 0.85 (range, 0.5-3.8 mg/dL). This difference, although statistically significant (P = .03), was not clinically important. Thirteen of 14 patients had no change in Child-Pugh class.
CT angiography can be used to delineate the blood supply and volume to a targeted hepatic segment, allowing superselective 90Y radioembolization. This approach significantly increases effective 90Y tumor radiation dose without clinically altering liver function or Child-Pugh class.
Journal of Vascular and Interventional Radiology 09/2005; 16(8):1085-91. · 2.08 Impact Factor
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ABSTRACT: Adult-to-adult living donor liver transplantation (ALDLT) is being increasingly utilized to treat patients with locally advanced hepatocellular carcinoma and cholangiocarcinoma who are not prioritized under the MELD allocation system. A single institution retrospective chart review examined ALDLTs performed for malignancy to identify indications, complications, and transplant outcome. Since 1997, 18 ALDLTs have been performed for malignancy as the primary indication. Thirteen patients were transplanted for HCC. The median survival following transplant was 18.6 months and four patients developed recurrent HCC. Five patients were transplanted for cholangiocarcinoma, with a 100% recurrence free survival at a mean follow up of 18 months among patients given neo-adjuvant chemoradiation. ALDLT can be safely performed for malignancy with an acceptable peri-operative mortality rate. However, HCC patients with large tumors experience a high rate of recurrence. The use of ALDLT for cholangiocarcinoma appears promising specifically in the context of neo-adjuvant therapy.
Transplantation 03/2005; 79(3):363-6. · 4.00 Impact Factor
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ABSTRACT: Caspases are a conserved family of proteases that play a critical role in the execution of apoptosis by cleaving key cellular proteins at Asp residues and modifying their function. Using an expression cloning strategy we recently developed, we isolated human RAD21/SCC1/MCD1 as a novel caspase substrate. RAD21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand DNA breaks. Interestingly, RAD21 is cleaved by a caspase-like Esp1/separase at the onset of anaphase to trigger sister chromatid separation. Here, we demonstrate that human RAD21 is preferentially cleaved at Asp(279) by caspases-3 and -7 in vitro to generate two major proteolytic products of approximately 65 and 48 kDa. Moreover, we show that RAD21 is specifically proteolyzed by caspases into a similarly sized 65-kDa carboxyl-terminal product in cells undergoing apoptosis in response to diverse stimuli. We also demonstrate that caspase proteolysis of RAD21 precedes apoptotic chromatin condensation and has important functional consequences, viz. the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal. Taken together, these findings point to an entirely novel function of RAD21 in the execution of apoptosis.
Journal of Biological Chemistry 06/2002; 277(19):16775-81. · 4.77 Impact Factor
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ABSTRACT: Colorectal cancer is the third most common human malignancy. Direct observation and biopsy sampling by colonoscopy have provided unique opportunities to study the natural history of the disease. As a consequence, advances in the understanding of colorectal cancer pathogenesis have evolved more rapidly than with most other solid tumours. Numerous molecular events arising during the development of colorectal cancer have been sorted out over the past two decades. Despite these advances, predicting outcome and response to therapy is still a major challenge in the management of patients with colorectal cancer. Molecular and biochemical markers of colorectal cancer are greatly needed for diagnosis and prognosis as well as for the selection and monitoring of treatments. The purpose of this chapter is to provide a critical assessment of the usefulness of markers in the prognosis and prediction of response to treatment in colorectal cancer.
Baillière' s Best Practice and Research in Clinical Gastroenterology 05/2002; 16(2):331-45. · 2.46 Impact Factor
