Cancer | Clinical Briefings™ & Clinical Reports from Penn Medicine

Transanal Endoscopic Microsurgery for Lesions of the Mid to Upper Rectum

2011-12-01T07:38:00.002-05:00

Penn colon and rectal surgeons are now using transanal endoscopic microsurgery (TEM) to excise advanced polyps and selected early cancers (ultrasound T1) in the mid to upper rectum.

A minimally invasive approach, TEM permits surgeons to reach lesions up to 10-15 cm from the anal verge and to remove whole tumors while sparing the function of the rectum. The procedure employs an operating proctoscope through which instruments are introduced to perform excision and other functions under direct three-dimensional magnified visualization of the operating field.

The objectives of rectal cancer surgery include sphincter preservation, prevention of disease recurrence and long-term survival. Oncologic surgical principles require removal of the tumor-bearing organ, along with all nodal tissue. These operations may involve significant morbidity in terms of recovery from surgery, the possible need for temporary or permanent stomas and in post-operative function.

Local excision may be appropriate for advanced polyps and certain early cancers given the very low likelihood of nodal involvement (<10 percent in many early cancers) and has traditionally been employed for the purposes of polyp removal in low rectal polyps and for diagnosis in indeterminate lesions that are otherwise not amenable to colonoscopic removal.

However, most lesions of the mid to upper rectum are inaccessible to local excision using standard instruments. In patients having standard transanal excision, incomplete removal or fragmentation of excised lesions accounts for recurrence rates as high as 30 percent.

The advantages of TEM relative to standard cancer operations include rectal preservation, less blood loss, less pain, fewer complications and a faster recovery time. When compared to standard transanal excision, TEM results in superior visualization and less tissue fragmentation. This results in a significantly decreased recurrence rate for both adenomas and selected early
cancers.

Case Study

Mrs. M, a 58-year-old woman, was referred to the division of Colon and Rectal Surgery at Penn following two months of diarrhea and acute pain when a sigmoidoscopy revealed a large villous adenoma on the right wall of the mid rectum. At Penn, an ultrasound of the lesion found no evidence of invasion; a subsequent biopsy suggested that the lesion was benign.

Although all villous adenomas are considered premalignant and should be removed, the lesion was not amenable to removal by conventional colonoscopy. A transanal endoscopic microsurgery
was scheduled to remove the lesion.

The procedure was performed in approximately 90 minutes under general anesthesia with no complications. Intraoperative biopsies revealed clear surgical margins and no invasive disease. Mrs. M was mobile on the day of surgery and was discharged the next day. At her one year follow-up, no evidence of disease was present.

Faculty Team

The Division of Colon and Rectal Surgery at Penn Medicine provides the highest quality diagnostic and surgical options for patients with colon, rectal and anal cancer, inflammatory bowel disease (Crohns disease and ulcerative colitis), diverticular disease and many other diseases and disorders of the colon, rectum and anus.

The division offers (anal) sphincter-preserving colon and rectal surgery for cancer and benign disease, laparoscopic colon surgery, surgery for anal incontinence and rectal prolapse and both operative and medical therapies for anal diseases and complaints.

Performing Transanal Endoscopic Microsurgery at Penn Medicine

Joshua I.S. Bleier, MD, FACS, FASCRS
Assistant Professor of Surgery

Colon & Rectal Surgeons

Robert D. Fry, MD, FACS, FASCRS
Chairman, Department of Surgery, Pennsylvania Hospital
Chief, Division of Colon and Rectal Surgery
Emilie & Roland de Hellebranth Professor of Surgery

Cary Aarons, MD
Assistant Professor of Surgery

Brian R. Kann, MD, FACS, FASCRS
Assistant Professor of Surgery

Najjia N. Mahmoud, MD, FACS, FASCRS
Associate Professor of Surgery

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Department of Surgery
Hospital of the University of Pennsylvania
4 Silverstein
3400 Spruce Street
Philadelphia, PA 19104

Department of Surgery
Penn Presbyterian Medical Center
Wright Saunders
Suite 266
51 N 39th Street
Philadelphia, PA 19104

Department of Surgery
Pennsylvania Hospital
Garfield Duncan Building
Suite 305
700 Spruce Street
Philadelphia, PA 19106

Download a pdf of this Clinical Briefing.

Proton Radiotherapy for Recurrent Cancers

2011-11-29T10:13:00.002-05:00

Radiation oncologists at Penn Medicine are conducting a clinical trial to determine the feasibility of proton radiotherapy (PRT) as a modality for the treatment of previously radiated patients with histologically confirmed, non-CNS solid malignancies and tumor recurrence in or near prior radiation fields. The study (ClinicalTrials.gov Identifier: NCT01126476) includes five cohorts: recurrent cancers of the head and neck, thorax, abdomen, pelvis and extremities.

The challenge when considering curative or aggressive local control of previously irradiated recurrent tumors is that photon beam radiotherapy (including intensity-modulated radiation therapy or IMRT), carries significant risk for organs at risk from the cumulative effects of radiation.

Unlike photon beam radiotherapy, protons deposit the bulk of their energy only at the end of their path. Thus, proton radiotherapy may offer potential dosimetric and clinical advantages compared to photon radiation in patients experiencing recurrent cancers.

The first phase of the current study at Penn studies the feasibility of re-irradiation in each of the cohorts. In cohorts where feasibility has been verified, patients can then be enrolled in the second registration phase of the study. The study evaluates patients for both acute and late toxicity.

For more information about this study, contact: John Plastaras, MD, PhD at 215-615-3714 or admin@ctsrmc.org.

The initial findings from a prospective dosimetric analysis of PRT versus IMRT in pelvic tumors were presented at the 53rd annual meeting of the American Society for Therapeutic Radiology and Oncology in October 2011.

Prospective Trial of Proton Re-Irradiation of Recurrent Pelvic Tumors: Dosimetric Analysis*

Objectives: To provide an initial dosimetric analysis of PRT versus IMRT in pelvic tumors and an acute adverse effects profile for these patients. The primary endpoints were feasibility and acute toxicity.

Methods: All patients (N=10) were adults with solid tumor recurrences in or near prior radiation fields treated at least three months prior to entering the study. Malignancies included rectal adenocarcinoma, sarcoma and cervical carcinoma. Patients were further stratified by treatment volume as either low volume CTV (<250 cc, n=6) or high volume CTV (>250 cc, n=4). Fifty percent of patients received concurrent chemotherapy as 5-FU-based treatment (N=4) or cisplatin (N=1). IMRT plans were generated for backup purposes, and were optimized to deliver the same biologically equivalent dose as the PRT plans. IMRT and PRT plans were compared.

Results: Early findings suggest that in the prospective setting, PRT for the re-irradiation of recurrent pelvic malignancies reduces dose to many critical OARs when compared with intensity-modulated radiotherapy (IMRT) including bowel dose.

*Abigail Berman Milby MD, Stefan Both PhD, Tiffany Sharkoski BA, James M. Metz MD,
Smith Apisarnthanarax MD, Zelig Tochner MD, John P. Plastaras MD, PhD. Department of
Radiation Oncology, University of Pennsylvania, Philadelphia, PA.

Faculty Team
Among the largest and most respected programs in the world, Penn Radiation Oncology offers a variety of innovative treatment options to patients with cancer. In addition, as a national leader in basic science, translational research and clinical trials, Penn Radiation Oncology offers patients access to the latest treatment options––including proton therapy––before they are widely available elsewhere.

Performing Clinical Research in Proton Therapy for Recurrent Cancers at Penn Medicine

James M. Metz, MD
Clinical Director, Department of Radiation Oncology
Associate Professor of Radiation Oncology

John P. Plastaras, MD, PhD
Assistant Professor of Radiation Oncology

Zelig A. Tochner, MD
Professor of Radiation Oncology

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Penn Radiation Oncology
Perelman Center for Advanced Medicine
Concourse Level
3400 Civic Center Boulevard
Philadelphia, PA 19104

Abramson Cancer Center
Penn Presbyterian Medical Center
Medical Arts Building, Suite 103A
51 N 39th Street
Philadelphia, PA 19104

Pancreatic Cancer Research

2011-09-22T08:26:00.002-04:00

From the Penn GI News, Summer 2011

Pancreatic cancer is the second most common gastrointestinal malignancy and the fourth leading cause of cancer-related deaths in the United States. Because the majority of patients are diagnosed late in the course of the disease, the prognosis for pancreatic cancer is dismal. More than 95 percent of patients die within five years of diagnosis. There is thus a great need to discover early methods of detection for the disease.

The molecular pathogenesis of pancreatic cancer is being elaborated at Penn and elsewhere, and is known to include mutations of the K-ras oncogene (seen in 90 percent of pancreatic adenocarcinomas), the Hedgehog signaling pathway and the inactivation of the tumor
suppressor genes p53 and p16/Ink4a, among others.

At Penn's Division of Gastroenterology, researchers Andrew Rhim, MD, and Ben Stanger, MD, have been investigating oncogentic mutations to identify biomarkers with the potential to aid in the early diagnosis of pancreatic cancer. Their study is representative of recent research in pancreatic cancer at Penn Medicine.

Epithelial-to-mesenchymal transition and hematogenous dissemination precedes histologic diagnosis of pancreatic cancer
Primary Investigators at Penn: Andrew Rhim, MD, Ben Stanger, MD. Contact: andrew.rhim@uphs.upenn.edu; stanger@exchange.upenn.edu

Background: Metastatic disease is the predominant mode by which cancer, and, particularly pancreatic cancer, kills patients. Indeed, the vast majority of those who are diagnosed with pancreatic cancer also have metastatic disease upon presentation. Of those with limited or small tumors and no radiographic evidence of metastases, many will undergo surgical resection; however, up to 90 percent of all of these patients will eventually succumb to metastatic disease.

These clinical observations thus suggest that the seeds of metastatic disease may be established long before pancreatic tumors are detected, or perhaps, form. The current study tests the hypothesis that pancreatic cell dissemination into the blood stream and colonization of distant organs occur prior to tumor formation.

Objectives: To determine when during cancer progression epithelial-to-
mesenchymal transition (EMT), a molecular reprogramming event thought to be required for the first steps of metastasis; hematogenous dissemination; and distant organ colonization occurs.

Methods: Two unique lineage-labeled mouse models of spontaneous pancreatic ductal adenocarcinoma (PDAC) were created to study the fate of pancreatic epithelial cells during various stages of tumor progression.

Both models relied on the Pdx1-Cre transgenic strain to generate pancreas- specific mutations in Kras and either p53 or P16ink4a/Arf, genes that are mutated with high frequency in human pancreatic cancers.

The Rosa26YFP allele was introduced in both groups to track the fate of pancreatic epithelial cells, resulting in highly specific and efficient fluorescent labeling (>95% of all pancreatic epithelial cells). Pancreas and blood specimens were analyzed from 1) “PanIN” mice with only the precancerous pancreatic intraepithelial neoplasia (PanIN) lesion and no histologic evidence of cancer by hematoxylin and eosin (H&E) staining [aged 2-2.5 mo] and 2) “PDAC” mice harboring pancreatic tumors [aged 3.5-4 mo].

Expression of the markers Zeb1 and Fsp1 (independent predictors of mortality in pancreatic cancer) and the absence of epithelial markers E-cad and CK19 were used to detect EMT in YFP+ pancreatic epithelially derived cells as mesenchymal markers. Fluorescent pancreatic cells in the blood stream and the liver were detected using flow cytometry (FACS) analysis
and immunofluorescent staining of liver sections.

Results: Multicolor immunofluorecent (IF) staining for the YFP epithelial lineage label and the mesenchymal markers Zeb1 and FSP1 revealed double positive (EMT+) cells residing in 2.2% and 17.4% of all PanIN2 and PanIN3 (low- and high-grade dysplasia) lesions, respectively.

Further, individual spindle-shaped YFP+ cells were observed invading into the pancreatic stroma of PanIN mice, despite the absence of a pathologic diagnosis of cancer based on H&E staining. Using FACS, YFP+ pancreatic cells were found in the blood of both tumor-bearing PDAC mice and PanIN mice (94.5 ± 35.4 v. 42.9 ± 20.5 cells/ml blood; p<0.001; n=30) but not in control Pdx-Cre;RosaYFP mice.

These circulating YFP+ cells were devoid of CD45 and Ter-119 (markers of white and red blood cells), expressed YFP, E-cadherin and Pdx-1 transcripts, and formed pancreatospheres in attachment-free cultures, a surrogate test for cancer stem cells. Finally, while rare individual YFP+ cells were found in small hepatic venules of PanIN mice, no metastatic lesions were appreciated, such as those seen in PDAC mice.

Conclusions: Using sensitive genetic tools, this study offers evidence that EMT, invasion, and hematogenous dissemination precede conventional histologic diagnosis of PDAC. These data argue against the classical linear progression model of cancer, whereby dissemination occurs after tumors form. Further, it suggests that current tools that are being used to diagnose carcinoma on biopsy specimens may not be sensitive enough to detect the earliest stages of cancer.

However, it is still unclear if circulating PanIN cells are the source of metastatic lesions. Nevertheless, based on this data, circulating pancreatic cells may be specific biomarkers for advanced PanIN disease and early pancreatic carcinoma. Clinical trials are planned to translate these results to humans.

PANCREATITIS RESEARCH AT PENN

Acute & Chronic Pancreatitis

Chronic pancreatitis (CP) accounts for 80,000 hospital admissions annually in the United States at an estimated annual cost of $2.5 billion.1 Many patients with chronic pancreatitis are disabled from pain and their disease, leading to far greater indirect costs.

Alcohol, smoking and very high triglyceride levels are strong predictors for the development of CP, but the cause of the disease remains unknown in 20 percent of patients even after careful investigation. Among other objectives, clinical research at Penn Gastroenterology is focusing on the race-dependent risk factors for pancreatitis and the identification of biomarkers that will determine the malignant potential of pancreatic cystic neoplasms.

North American Pancreatitis Study 2 (NAPS2): Race-dependent Genotype-phenotype Associations for the Development of Chronic Pancreatitis and Its Subtypes

Primary Investigator: John G. Lieb II, MD. Primary
Contact: Amina A. Wirjosemito, MPH (amina.wirjosemito @uphs.upenn.edu).

Background: In the United States, the rate of chronic and acute pancreatitis among African Americans is about twice that of the white population.2 Only 58 of 1000 patients with CP enrolled in the NAPS2 study were African-American, however, resulting in a sample size insufficient for subset analyses. This study will enroll a cohort of African-American patients with CP of sufficient size to permit comparisons with the NAPS2 dataset.

Objectives: To identify/quantify genetic, epidemiologic, social, medical, surgical, environmental and novel risk factors that lead to the development of nonfamilial CP, especially in African-Americans. To subclassify those risk factors for subtypes of CP (calcific, atrophic, mass-like, minimal-change, and so on) and to make genotype-phenotype associations in CP patients. To quantify pain and quality of life patterns in these CP subtypes in African- Americans and try to correlate those to genotypes.

Methods: This is a multicenter prospective cohort study performed as an ancillary to the North American Pancreatitis Study 2 (NAPS2) using that trial’s parameters, including lifestyle, environmental, clinical and imaging data, to subclassify CP in African-Americans. A linked biorepository (serum and DNA) will also be established. These sporadic patients will be tested for known variations in major susceptibility genes for chronic pancreatitis, as well as for associations with genes hitherto unknown to be related to CP (genome wide association studies). These initial genotyping efforts will support analysis of gene-environment interactions to identify specific risk factors and optimal treatment options in African-Americans and permit comparisons with the NAPS2 dataset.

Pancreatic CystsResearchers with the Division of Gastroenterology at Penn Medicine are working with the Department of Pathology to investigate ways to better diagnose and differentiate pancreatic cysts and their progression.

Mesothelin: A Potential Biomarker for the Diagnosis of Mucinous Cystic Lesions of the Pancreas
Principal Investigators: Nuzhat Ahmad, MD; Nirag Jhala, MD. Primary Contact: Pari Shah, MD, — pari.shah@uphs.upenn.edu.

Background: Optimal management of pancreatic cystic neoplasm depends upon accurate diagnosis. Because it can be difficult to differentiate pancreatic cysts without malignant potential, (i.e., pancreatic pseudocysts) from cysts with high malignant potential, such as mucinous cystadenoma, cystadenocarcinoma and intraductal papillary mucinous tumors (IPMTs), pancreatic cystic neoplasms present a diagnostic dilemma. Over-expression of the protein mesothelin has been shown to be associated with invasive intraductal papillary mucinous neoplasia (IPMN) and hence can potentially be used as a marker to predict aggressive behavior of cysts.

Objective: The purpose of this study is to determine if mesothelin expression can be used to differentiate mucinous cystic lesions with low malignancy potential from those with high malignancy potential, as well as predict the malignant potential of mucinous lesions of the pancreas.

Methods: This study will involve developing a database to perform a retrospective review of all patients who underwent resection for cystic lesions of the pancreas between 2001 and 2009 at the Hospital of the University of Pennsylvania. From this cohort, 20 patients will be randomly selected with MCN, IPMN, mucin secreting adenocarcinoma, serous cystadenoma and pseudocysts. Patients may also have prior cytology samples from cyst aspirates.

This selection will be stratified by type of dysplasia (low-grade dysplasia — high-grade dysplasia) and adenocarcinoma. Expression pattern of mesothelin in gastric foveolar, as well as duodenal, mucosal cells will also be determined. Adjacent normal pancreatic tissue will serve as the control for each specimen. Immunohistochemical assays will measure mesothelin expression in each tissue sample.

References: 1. Lowenfels, et al. Curr Gastroenterol Rep. 2005;7:90-95. 2. Yang AL, et al. Arch Intern Med. 2008;168:649-656.

To refer a patient to Penn Medicine, please contact Penn PhysicianLink^TM here or at 877-937-7366.

Download the Summer 2011 Penn Gastroenterology News.

Clinical Research in Ovarian Cancer Immunotherapy

2011-07-13T10:07:00.002-04:00

Researchers at the Penn Ovarian Cancer Research Center (OCRC) are expanding their immunotherapy program to offer state-of-the-art personalized therapy to patients with recurrent ovarian, primary peritoneal and fallopian tube cancers.

Patients with these malignancies may be eligible to enter advanced clinical trials in immunotherapy to investigate the use of vaccines manufactured from the patient’s own tumor followed by T cells expanded in culture from peripheral blood.

Despite intense efforts to improve chemotherapy for ovarian cancer, no significant progress has been made over the past 30 years;survival rates have not changed in the past decade. Novel therapeutic approaches are direly needed.

Stimulating the immune system to attack tumors is not a new concept. What is new, however, is combining personalized vaccines based on autologous tumor with potent immune stimulators and post vaccine lymphocyte reinfusion. The underlying notion is that tumors are different enough from the normal body, such that they can be recognized and attacked as “foreign” or “non-self ” by the host’s immune system, once the latter is properly educated and activated.

Researchers at the Penn OCRC are currently conducting three phase I/II clinical trials for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer using autologous vaccines developed from patients’ autologous tumor.

One vaccine protocol administers intranodally autologous dendritic cells loaded with autologous tumor lysate, in combination with bevacizumab (UPCC-19809). Patients must have a tumor lesion of >2 cm.

Another protocol administers tumor lysate intradermally in combination with an immunomodulatory drug, Toll-like receptor 3 (Ampligen) (UPCC-29810). Patients must be HLA-A2+ with a largest tumor lesion of <2 cm. Patients with recurrent disease are eligible, although tumor from primary debulkings can be banked for future use.

The third clinical trial works on the hypothesis that antitumor immune response generated by a vaccine can be significantly augmented by infusion of autologous activated lymphocytes. Accelerated recovery of CD4+ and CD8+Tcell counts would occur in the setting of lymphopenia in the wake of the adoptive transfer of in vivo vaccine-primed T cells in combination with bevacizumab (UPCC 26810). This trial is a sequential trial following the above vaccine studies. Eligible patients are those vaccinated with autologous vaccine.

In a pilot study that was completed in 2010, patients with recurrent progressive stage III and IV ovarian cancer with available tumor lysate from secondary debulking surgery underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with autologous tumor lysate (5-10x10e6 DC per dose, 3 doses) plus bevacizumab (two doses).

This was followed by lymphodepletion using high-dose outpatient cyclophosphamide and fludarabine (cy/flu, 300 and 30 mg/m2/day, respectively, x 3 days) and transfer of 5x10 e9 autologous vaccineprimed, ex vivo CD3/CD28-costimulated peripheral blood T cells, in combination with vaccination.

Feasibility, safety, and biological and clinical efficacy were evaluated. Three subjects have completed vaccination and T cell transfer, while three additional subjects completed vaccination only. Therapy was feasible and well tolerated as an outpatient regimen. Vaccination following bevacizumab and metronomic cyclophosphamide preconditioning elicited vaccine-specific T cell response in four patients. Clinical benefit was seen in four out of six patients after vaccination where two subjects had partial response, two had stable diseases.

Following outpatient cy/flu lymphodepletion, adoptive transfer of vaccine-primed, CD3/CD28-costimulated autologous T cells resulted in clinical response in two of three patients, with one patient achieving CR. No toxicities were seen.

Case Study

Mrs. T, a 46-year-old woman, was diagnosed with stage 2C ovarian cancer and had her first debulking surgery in October 2007. She was then placed on carboplatinum/taxol standard of care chemotherapy. In December 2008, she recurred and underwent a secondary debulking surgery. She then received radiation followed by bevacizumab and cyclophosphamide.

Mrs. T recurred again in June 2009 and was debulked for the third time a month later. At this time, her tumor tissue (which would normally have been discarded) was used to create a personalized autologous vaccine. Mrs. T enrolled in a pilot vaccine study at Penn in November 2009.

She underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with autologous tumor lysate plus bevacizumab. After completing this trial, she went on to receive additional maintenance vaccines, then reenrolled in the current vaccine trial (UPCC19809) in September 2010 and completed this trial in January 2011.

Mrs. T continued to receive maintenance vaccine until May 2011. She is currently disease-free, and has had no evidence of disease since entering the immunotherapy program at Penn in November 2009.

Penn Ovarian Cancer Research Center Now Storing Tumor Tissue
for Non-Penn Medicine Patients

Originally, the Penn Ovarian Cancer Research Center (OCRC) had restricted its immunotherapy program to patients who completed surgery at Penn Medicine. Now, Penn is accepting tumor tissue even when the surgery is performed at outside institutions. A patient who has surgery at her local hospital can have her tumor tissue shipped to the OCRC, where it is processed and stored live for future immunotherapy.

For more information, please contact us at 215-615-6727 or via email at lknd@mail.med.upenn.edu.

Faculty Team

The Penn Ovarian Cancer Research Center (OCRC) is a joint effort of the research and clinical facilities of the Perelman School of Medicine at the University of Pennsylvania, the Abramson
Cancer Center and the Department of Obstetrics and Gynecology.

The goal of the OCRC is to identify new methods to detect, prevent and treat ovarian cancer and to improve the quality of life for women with the disease. The Faculty of the Penn Ovarian Cancer Research Center includes world-renowned clinicians and researchers with a commitment to the investigation of novel, advanced approaches to the diagnosis and treatment of ovarian cancer.

Performing Research in Ovarian Cancer at the Penn Ovarian Cancer Research Center

Janos L. Tanyi, MD
Assistant Professor of Obstetrics and Gynecology

Lana E. Kandalaft, PharmD, PhD
Director of Translational Research and Clinical Development

Daniel J. Powell, Jr., PhD
Research Assistant Professor of Pathology and Laboratory Medicine

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Jordan Center for Gynecologic Cancer
Abramson Cancer Center
Perelman Center for Advanced Medicine,
West Pavilion, 3rd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

To find more information about clinical trials at the
Penn Ovarian Cancer Research Center, visit:
http://www.uphs.upenn.edu/obgyn/research/ovarian.htm

Download a pdf of this Clinical Briefing.

Management of Hepatocellular Carcinoma

2011-05-02T14:34:00.002-04:00

Hepatologists, surgeons, medical oncologists, interventional radiologists, radiologists and radiation oncologists at Penn Medicine are treating patients with hepatocellular carcinoma and those at risk for the disease.

Hepatocellular carcinoma (HCC) is an increasingly prevalent problem in the United States. Hepatitis C-associated HCC is likely the major culprit for a dramatic increase in HCC incidence and mortality in the past two decades.1

There are many treatment options for patients with hepatocellular carcinoma.2 Since early detection offers the best opportunity for cure, screening for HCC in patients with cirrhosis is of utmost importance and is often a key determinant of outcome.

Surgical resection of the tumor can achieve cure of HCC, particularly when the tumor is small and liver function is preserved. With partial hepatectomy, there is always concern for development of another HCC in the remaining diseased liver, which can happen in up to 50-70 percent of cases. Liver transplantation is often the most effective treatment for HCC, if the tumor is within a certain stage.

Because the entire liver is replaced, liver transplant circumvents the strict need for good liver function that surgical resection requires. The other major advantage of transplantation is that it results in removal of the tumor as well as removal of the rest of the liver which, if left behind, will remain at risk of developing additional tumors. The result is that the recurrence rate of HCC after transplantation is 10-20%, much lower than after resection. A select group of patients with small, favorably located tumors can be cured with ablative therapies, such as percutaneous or laparoscopic radiofrequency ablation.

Effective treatment for HCC is possible also in patients with more advanced disease. Trans-arterial chemoembolization (TACE), in which a chemotherapy mixture is injected directly into the tumor and its blood supply is interrupted, results in tumor death and is effective at controlling even larger tumors.

TACE is also useful to prevent tumors from growing while patients with smaller tumors are on the liver transplant waiting list. Radioembolization involves the injection of radiation-emitting beads into the tumor and is often an alternative option to TACE. Systemic chemotherapy in the form of the oral drug Sorafenib or clinical trials with newer drugs are also effective treatment options in advanced disease.

Navigating the various treatment options in HCC can be complex and requires the expertise of physicians with different areas of specialization. At Penn, patients presenting with liver tumors are discussed every week by a multidisciplinary team of specialists in the context of a conference. Patients are then evaluated by multiple physicians and surgeons with expertise in liver cancer and liver disease in a single visit to the Penn Liver Tumor Clinic where treatment options are discussed.

The liver tumor team at Penn has the unique capability of an efficient and expert evaluation of patients, and is committed to offering convenient access to skilled medical and surgical care of a complex disease.

Case Study

Mr. A is a 53-year-old teacher with chronic hepatitis C-related cirrhosis who recently failed standard therapy for hepatitis C. He has no symptoms of liver disease, and has only small varices on an upper screening endoscopy. He has no other medical history and works full time. On an ultrasound of the liver obtained for screening, a 2.5 cm mass was found. AFP was normal. An MRI of the liver was performed (Figure 1).

Mr. A’s case was discussed in the Penn Multidisciplinary Liver Tumor Conference. Review of the films confirmed a diagnosis of hepatocellular carcinoma by imaging characteristics; no biopsy for confirmation was warranted. Treatment options were discussed. Since the location of the lesion would require a right hepatectomy and the presence of varices indicated portal hypertension, it was felt that resection would carry a high risk of liver failure.

The potential for the less invasive treatment option of radiofrequency ablation was discussed, but it was felt that this would be a suboptimal treatment in his case because he would be an excellent transplant surgical candidate.

Mr. A was seen in consultation in liver tumor clinic concurrently by a hepatologist, a transplant/hepatobiliary surgeon and an interventional radiologist. The risks, benefits and alternatives of the different treatment options were discussed. After reviewing his options, the patient elected to pursue liver transplantation. He completed a liver transplant evaluation and was listed for transplantation.

To prevent the tumor from growing while waiting for transplantation, TACE was performed. Partial tumor necrosis was achieved and the lesion remained stable in size until he received a transplant, about 9 months after being listed.

Pathology of the explanted liver showed moderately differentiated HCC in the right lobe, 2.8 cm in size; about 70% of the nodule was necrotic and there was no evidence of vascular invasion. The patient was enrolled in a surveillance program for recurrent disease, with serial imaging of the chest and abdomen. At 18 months post transplant, there is no evidence of recurrent HCC and the patient is asymptomatic.
References
1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and
molecular carcinogenesis. Gastroenterology. 2007;132:2557-2576.
2. Mendizabal M, Reddy KR. Current management of hepatocellular carcinoma.
Med Clin Nor Am. 2009;93:885-900.

Team of Faculty
The Penn Liver Tumor Clinic brings together a multidisciplinary team of physicians, nurse specialists and hospital support staff who provide coordinated care throughout the treatment process. The goal is to meet the unique physical and emotional needs of each patient in a caring, professional environment.

Hepatologists

K. Rajender Reddy, MD,
Director of Hepatology
Medical Director of Liver Transplantation

Kimberly A Forde, MD, MHS
Assistant Professor of Medicine

Maarouf A. Hoteit, MD
Assistant Professor of Clinical Medicine

David E. Kaplan, MD, MSc
Assistant Professor of Medicine

George A. Makar, MD , MSCE
Associate Professor of Clinical Medicine

Transplant and Hepatobiliary Surgeons

Abraham Shaked, MD, PhD
Director, Penn Transplant Institute

Kim Olthoff, MD
Director, Liver Transplant Program

Peter L. Abt, MD
Associate Professor of Surgery

Matthew H. Levine, MD, PhD
Assistant Professor of Surgery

Medical Oncologists

Bruce Giantonio, MD
Associate Professor of Medicine

Nevena Damjanov, MD
Associate Professor of Clinical Medicine

Ursina R. Teitelbaum, MD
Deenie Greitzer and Daniel G. Haller Associate Professor

Radiologists

Mark A. Rosen, MD, PhD
Associate Professor of Radiology

Evan S. Siegelman, MD
Associate Professor of Radiology

Interventional Radiologists

Michael Soulen, MD
Professor of Radiology in Surgery

S. William Stavropoulos, MD
Professor of Radiology

Jeff Mondschein, MD
Associate Professor of Clinical Radiology

Mandeep S. Dagli, MD
Assistant Professor of Clinical Radiology

Radiation Oncologists

Robert Lustig, MD
Professor of Clinical Radiation Oncology

John P Plastaras, MD, PhD
Associate Professor of Radiation Oncology

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The Penn Transplant Institute
Liver Tumor Clinic
Perelman Center for Advanced Medicine
West Tower, 2nd Floor
Philadelphia, PA 19104

Calypso® System Tracking and Target Localization during Radiotherapy for Prostate Cancer

2010-10-08T14:24:00.002-04:00

The Hospital of the University of Pennsylvania was the third institution in the country to install the Calypso 4D Localization System^TM to guide radiation therapy for prostate cancer. Calypso employs radiofrequency technology comparable to the Global Positioning System to continuously and precisely monitor biologically inert transponders implanted in the prostate. By tracking these small electromagnetic sensors, Penn radiation oncologists are able to target tumors in real time.

Precise tracking of the prostate during radiation therapy is of critical importance because the organ is prone to constant displacement. This affects both treatment success and the proportion of unwanted radiation exposure to normal tissues.

Prostate displacement occurs frequently during radiation treatment. A recent study¹ of the Calypso System concluded that on average, the prostate was displaced in patients receiving radiation therapy by more than 3 mm for 13.6 percent of the total treatment time. For 3.3 percent of the total treatment time, displacement exceeded 5 mm.

During Calypso therapy, radiation oncologists are able to precisely monitor movement of the prostate. When prostate displacement exceeds predetermined thresholds, (i.e., 5 mm for more than 10 seconds) treatment can be halted temporarily to readjust the patient’s position.

This process increases the precision of each treatment, permitting a greater impact on target cells and fewer residual effects on normal tissue.

"The Calypso System's continuous real-time tracking data permit radiation oncologists to know where the prostate is during external beam radiation treatment with far greater precision than has ever been possible before. This information helps us to target prostate cancer more accurately for daily radiation, while helping to minimize potential side effects of therapy. Overall, this should lead to improved outcomes in terms of both tumor control and quality of life."

Neha Vapiwala, MD

1. Langen KM, Willoughby TR, Meeks SL, et al. Observations on real-time prostate gland motion using electromagnetic tracking. Int J Radiat Oncol Biol Phys. 2008;71:1084-1090.

All Images © Calypso® Medical Technologies, Inc.

Our Team of Faculty
Radiation Oncology at Penn is a national leader in clinical care, research, and education, and has one of the largest and most respected clinical services in the region. The department’s faculty provides comprehensive radiation therapy care in cooperation with surgeons, medical oncologists and other specialists to design management plans specific to each patient’s needs with the goal of achieving the best possible outcomes. The Calypso 4D Localization System is available through the collaborative efforts of the department of Radiation Oncology and the division of Urology at Penn.

Performing Calypso® 4DTM Localization System
Diagnostics at Penn

DEPARTMENT OF RADIATION ONCOLOGY
Neha Vapiwala, MD
Assistant Professor of Radiation Oncology

DIVISON OF UROLOGY
Alan J. Wein, MD
Chief, Division of Urology
Professor of Surgery

S. Bruce Malkowicz, MD
Professor of Surgery

Access
Patient appointments are available at:

Department of Radiation Oncology
2 Donner Building
3400 Spruce Street
Philadelphia, PA 19104

To refer a patient and/or consult
with a doctor:
Call 800-789-PENN(7366) or visit:
PennMedicine.org/referral

Download a pdf of this Clinical Briefing here.
(pdf will print at full resolution)