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Research

Research2019-10-30T17:30:02+00:00

USC Norris Westside Cancer Center

Located in Beverly Hills, the USC Norris Westside Cancer Center is a multi-disciplinary cancer clinic and clinical trials center. We work to provide care for patients with prostate and other genito-urinary cancers and bring innovative therapies to patients through clinical trials. Our goal is to make the most exciting and promising molecular targeted therapeutics available for our patients. Our team is comprised of medical oncologists, radiologists, radiation therapists and urologists.

The Radiomics Lab is a research group in the Department of Radiology at USC in Los Angeles. Our multidisciplinary team of radiologists, urologists, oncologists , engineers, researchers, programmers and statisticians are committed to developing image analysis tools, cutting-edge clinical workflows and aiding cost-effective and personalized precision medicine.

We focus on developing robust computational methods of extracting quantifiable features from medical images encompassing a wide range of imaging modalities and diseases. We have been able to extract and analyze a large amount of information relating to tumor behavior and tumor microenvironment and identify correlates and associations with genetic, molecular and pathological evaluation of tumors. In addition, we develop clinical decision support tools to aid diagnosticians to make more informed decisions about the diagnosis as well as the prognosis.

Epigenetic Translational Research Lab
Gangning Liang, MD, PhD
Director of Epigenetic Translational Research and Professor of Urology

Understanding the functional consequences of genetic and epigenetic alterations during tumorigenesis is important for diagnosis, prognosis, disease monitoring and personalized treatment. Our team works to not only develop epigenetic markers for diagnosis, prognosis and monitoring disease status but also to identify therapeutic targets in urological cancer.

DNA methylation markers for bladder cancer:
Our team has previously identified methylation markers that accurately predict bladder cancer recurrence in urine sediments (Su et al., Clinical Cancer Res. 2014). We also worked together with Zymo Research Corp. for the development of a noninvasive assay to measure bladder cancer–specific markers in urine sediment for diagnosis and prognostication. These can be collected without a patient clinic visit and can be especially useful for monitoring cancer recurrence and helping to determine response to chemotherapy and other intravesical treatments. Currently Dr. Siamak Daneshmand is leading clinic trials in these clinic applications.

DNA methylation markers for predication of aggressive prostate cancer:
Slow-growing prostate cancer (PC) can still be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. By working with Dr. Inderbir Gill, our team has developed a panel of DNA methylation for determining PC aggressiveness, with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to potentially determining candidates for focal therapy (Mundbjerg et al., Genome Biology 2017).

DNA methylation markers to distinguish subtype of kidney cancer:
The clinical management of small renal masses (SRM) is challenging, since the current methods for distinguishing between benign masses and malignant renal cell carcinomas are frequently inaccurate or inconclusive. In addition, renal cancer subtypes also have different treatments and outcomes. High false-negative rates increase the risk of cancer progression, and indeterminate diagnoses result in unnecessary and potentially morbid surgical procedures. Along with Dr. Inderbir Gill, our team has also developed a panel of DNA methylation markers that can be used in routine needle biopsies to determine tumor classification of SRMs and to support the clinical decision-making (Chopra et al., Oncotarget 2017).

Translational Genomics

We are deeply committed to excellence in translational genomics research, bringing to bear vast experience and expertise in molecular genetics, genome science, biomedical informatics, translational science and molecular medicine. Our ultimate goal is to serve the Keck Medicine of USC community, by bridging basic and clinical research through discovery and validation of novel diagnostics and therapeutics for earlier diagnosis and smarter treatments.

Early Complications After Cystectomy Following High Dose Pelvic Radiation

Authors: Manuel S. Eisenberg, Ryan P. Dorin, Georg Bartsch, Jie Cai, Gus Miranda, Eila C. Skinner

USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

PURPOSE: Radical cystectomy in patients with a history of pelvic radiation therapy (RT) is an often challenging and morbid procedure. We report early complication rates in patients undergoing cystectomy and urinary diversion (UD) after high dose pelvic radiation.

MATERIALS AND METHODS: From 1983 to 2008, 2629 patients underwent cystectomy with UD at a single institution.  Of these, 148 received ≥60 Gy pelvic RT  prior to surgery. Each patient’s medical record was retrospectively reviewed and any complication within 90 days of surgery was graded using the Clavien-Dindo system.

RESULTS: The median age was 74 years old, with a median ASA score of 3.  Patients received a median 70 Gy pelvic RT a median 2.3 years prior to surgery.  UD performed were ileal conduit in 65 (43.9%), continent cutaneous pouch in 35 (23.6%), and orthotopic neobladder in 48 (32.4%).  A total of 335 early complications were identified.  The highest grade complication was: none in 23%, grade 1 in 12.2%, grade 2 in 32.4%, grade 3 in 18.9%, grade 4 in 7.4%, and grade 5 in 6.1%.  Age >65 and ASA were statistically significant predictors of postoperative complications (p=0.0264 and p=0.0252, respectively). Type of UD did not significantly affect the grade distribution or number of early complications per patient (p=0.7444 and p=0.1807, respectively).

CONCLUSIONS: The early complication rate using a standardized reporting system in patients undergoing post-RT radical cystectomy is higher than previously published in non-irradiated subjects.  Age and ASA, but not urinary diversion type, are associated with early complications in this population.

Table 2: Patient clinical characteristics

Characteristic Median (% or IQR)
n 148
Age, years 74 (69-78)
Male 120 (81.1%)
ASA (n=122) 3 (3-3)
Radiation to surgery interval (years) 2.3 (1-9)
Total radiation dose 70 (65-100)
Indication for radiation therapy
   bladder cancer 79 (53.4%)
   prostate cancer 55 (37.2%)
   other* 14 (9.5%)
Previous abdominal or pelvic surgery (n=147) 95 (64.6%)
Preoperative systemic chemotherapy 39 (26.4%)
IQR, inter-quartile range; ASA, American Society of Anesthesiologists score*other indications for radiation therapy include cervical cancer, endometrial cancer, lymphoma, and carcinoma not otherwise specified

 

Table 6: Complication categories and types

Category Complication type (incidence*) n* % of total
Gastrointestinal Ileus† (29), dehydration (22), diarrhea (13), fistula / anastamotic bowel leak (9), failure to thrive (9), gastrointestinal bleeding (6), liver insufficiency/elevated LFT’s (4), emesis (3), dysphagia (3), small bowel obstruction (2) constipation‡ (2), large bowel obstruction (1) 103 30.7%
Infectious Sepsis (15), urinary tract infection (11), fever of unknown origin (7), urosepsis (6), C. difficile infection (5), abscess (4), oral candidiasis (2), cholecystitis (1), pyelonephritis (1) 51 15.2%
Bleeding Anemia requiring transfusion (28), internal hemorrhage (3), hematoma (2) 33 9.9%
Cardiac Arrhythmia (17), angina (4), myocardial infarction (3), congestive heart failure (3), hypertension (3), hypotension (1) 31 9.3%
Genitourinary (GU) / Diversion Urinary leak (7), renal insufficiency (4), urinary fistula (3), stomal incontinence (3), stomal ischemia/necrosis (3), acute tubular necrosis (2), ureteral obstruction (1), hematuria (1), renal failure (1), low urine output (1) 26 7.8%
Miscellaneous Edema (4), depression (4), electrolyte abnormality (3), rash (3), decubitus ulcer (2), other rare complications (10) 26 7.8%
Neurologic Altered mental status (18), neuropraxia (4), neuropathy (1), loss of consciousness (1) 24 7.2%
Pulmonary Respiratory distress (8), respiratory failure (6), atelectasis (4), pneumonia (2) 20 6.0%
Wound Seroma (10), superficial infection (6), fascial dehiscence (2) 18 5.4%
Thromboembolic Deep venous thrombosis (2), pulmonary embolus (1) 3 0.9%
LFTs, Liver function tests*Patients experiencing multiple complications are counted more than once†Ileus is defined as post-operative nausea or vomiting requiring the cessation of oral intake and/or nasogastric tube placement, or the intolerance of any oral intake by postoperative day 5.

‡Constipation is defined as the inability to have a bowel movement by postoperative day 5 without signs of ileus or bowel obstruction

 

Table 7: Complication categories by grade

Low Grade (n = 264) High Grade (n = 71)
Category n (%) Category n (%)
Gastrointestinal 81 (30.7%) Gastrointestinal 22 (31.0%)
Infectious 43 (16.3%) GU / Diversion 16 (22.5%)
Bleeding 30 (11.4%) Pulmonary 10 (14.1%)
Cardiac 26 (9.8%) Infectious 8 (11.3%)
Neurologic 23 (8.7%) Cardiac 5 (7.0%)
Miscellaneous 23 (8.7%) Bleeding 3 (4.2%)
Wound 16 (6.1%) Miscellaneous 3 (4.2%)
GU / Diversion 10 (3.8%) Wound 2 (2.8%)
Pulmonary 10 (3.8% Thromboembolic 1 (1.4%)
Thromboembolic 2 (0.8%) Neurologic 1 (1.4%)

 

Table 8: Statistical analysis of early complications (≤ 90days)

Univariate variable No Complications Any Grade 1-5 complication P value
n 34 114
Male 25 (73.5%) 95 (83.3%) 0.2002
Age >65yrs 24 (70.6%) 99 (86.8%) 0.0264
ASA (n=122) 0.0252
   1 2 (7.1%) 0 (0%)
   2 5 (17.9%) 17 (18.1%)
   3 20 (71.4%) 62 (66.0%)
   4 1 (3.6%) 15 (16.0%)
RT to RC interval (yrs, median) (IQR) 2 (1-10) 2 (1-8) 0.7035
RT dose (Gy, median) (IQR) 71 (65-100) 70 (65-136) 0.8925
Indication for XRT 0.8587
   bladder cancer 17 (50.0%) 62 (54.4%)
   prostate cancer 14 (41.2%) 41 (36.0%)
   Other 3 (8.8%) 11 (9.6%)
Prior abdominal or pelvic surgery (n=147) 22 (66.7%) 73 (64.0%) 0.7807
Prior neoadjuvant chemotherapy 9 (26.5%) 30 (26.3%) 0.9857
Extent of lymphadenectomy 0.3129
   Not performed 14 (41.2%) 35 (30.7%)
   <15 6 (17.7%) 34 (29.8%)
   ≥15 14 (41.2%) 45 (39.5%)
Diversion type 0.5681
   Ileal conduit 15 (44.1%) 50 (43.9%)
   Continent cutaneous 6 (17.7%) 29 (25.4%)
   Orthotopic neobladder 13 (38.2%) 35 (30.7%)
Operative time (hr, median) (IQR) 5 (5.0-6.0) 6 (5.0-7.0) 0.3238
EBL (ml, median) (IQR) 700 (600-1200) 1000 (700-1500) 0.1796

 

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