This image shows a tumor infused with fluorescent dye glowing under near-infrared light.
Figure 1: A small lesion (0.7 cm) appears under near-infrared light in the lower left lobe of a patient thought to have Stage IA pulmonary adenocarcinoma. The lesion was undetected by PET/CT scan and visual examination; this patient was subsequently re-staged to stage IIIA.

At Penn Medicine, surgeons are using molecular imaging technology to prevent cancer recurrence by improving the detection of residual cancer cells during surgery. 

Complete surgical resection is substantially more effective than chemotherapy or radiation therapy for almost all solid tumors, and surgery is the most important predictor of long-term survival in cancer patients in the United States. However, the overall success of cancer surgery is diminished by local recurrence in up to a third of patients.

Recurrence is typically due to malignant cells that remain in the surgical field even when the algorithm for their eradication involves meticulous resection at the surgical margins, excision of both involved lymph nodes and satellite lesions, and the use of intraoperative frozen sectioning by pathologists to ensure the complete eradication of cancer during surgery. That these efforts so often fail demonstrates the challenge of identifying invasive and occult cancer cells through traditional observation and palpation during surgery. 

To improve the long-term efficacy of cancer surgery, thoracic surgeons and radiation oncologists at Penn Medicine are using investigational intraoperative imaging systems that visually enhance residual cancer cells and the abnormal tissue densities typical of malignant lesions. These systems use fluorescent contrast agents that have an organic tropism for cancer cells, and that once absorbed, glow under certain lighting conditions, thus permitting lesions and cancerous cells to be identified and readily removed. 

Using these systems in separate applications during surgery, the team at Penn Medicine has identified nodules as deep as 1.3 cm from the surface of solid organs and as small as 0.2 cm in size, as well as nodules in organs other than that of the primary tumor. In addition, cancer cells that are invisible to optical observation have been identified at the margins of surgery in lung cancer patients. 

CASE STUDY 

Mrs. M, a 64-year-old woman, was referred to Penn Thoracic Surgery for evaluation following six-months of persistent cough and bronchial irritation. Mrs. M had never smoked, and with the exception of hypertension, her medical history was unremarkable. A chest x-ray at Penn revealed a mass (>3.5 cm) in the upper lobe of her left lung in close proximity to the pleura. A PET/CT scan found no evidence of spread to nearby lymph nodes or metastases.  

A transthoracic needle aspiration biopsy of the mass revealed malignant cells, and a histological analysis identified a moderately-differentiated cancer with clear cell features consistent with a primary pulmonary adenocarcinoma. Cytogenetic analysis was negative for EGFR/ Kras mutations and ALK rearrangement. There was no evidence of metastases. Mrs. M’s cancer was classified as a surgically resectable Stage IA pulmonary adenocarcinoma.  After a discussion during which Mrs. M expressed apprehensions about cancer recurrence based on personal experience, she provided her informed consent to take part in the fluorescent image-guided investigation.  

Prior to surgery, Mrs. M underwent CT scanning. The scan was reviewed by a radiologist to confirm the presence of a solitary pulmonary nodule. Twenty-four hours before her surgery, an intravenous contrast agent was administered.  During her surgery, surgeons located the identified primary nodule using visual inspection and manual palpation. Following an inspection of the ipsilateral lung that found no other lesions, the operating room lights were removed, and the near-infrared spectroscopy (NIR) imaging system was sterilely draped and positioned above the chest.  

The primary nodule was imaged and photo-documented by white light and fluorescence. The imaging system was then used to search for additional nodules in her lung, subsequently identifying a single small (0.7 cm) lesion in the lower lobe of her left lung (Figure 1) close to the pleural surface, and two lymph nodes near the original primary tumor. Both lesions and the lymph nodes were removed and re-imaged for confirmation in the operating room before being submitted to pathology. Mrs. M’s cancer was then re-staged to stage IIIA.  

Mrs. M remained in the hospital for two days following her surgery and was discharged home. Her recovery was unremarkable. She received adjuvant chemotherapy and radiation therapy without significant morbidity. At her six-month and one-year follow-up visits, x-rays and CT/PET scans found no evidence of recurrent cancer.

ACCESS

Harron Lung Center
Perelman Center for Advanced Medicine
West Pavilion, 1st Floor 
3400 Civic Center Boulevard
Philadelphia, PA 19104

Abramson Cancer Center
Perelman Center for Advanced Medicine
West Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Presbyterian Medical Center
51 N 39th Street
Philadelphia, PA 19104 
Pennsylvania Hospital
700 Spruce Street
Philadelphia, PA 19107

Published on: December 15, 2016

Penn Faculty Team

Keith Cengel, MD, PhD

Associate Professor of Radiation Oncology at the Hospital of the University of Pennsylvania

Associate Professor C-E

John P. Christodouleas, MD

Adjunct Assistant Professor of Radiation Oncology

Adjunct Assistant Professor

Andrew R. Haas, MD, PhD

Bronchoscopy Director, Hospital of the University of Pennsylvania

Director, Section of Interventional Pulmonology and Thoracic Oncology

Associate Professor of Medicine at the Hospital of the University of Pennsylvania

Associate Professor C-E

Doraid Jarrar, MD, FACS, FCCP

Assistant Professor of Clinical Surgery

Assistant Professor AC

John C. Kucharczuk, MD

Chief, Division of Thoracic Surgery

Associate Professor of Surgery at the Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Philadelphia and the Pennsylvania Hospital

Associate Professor C-E

Corey J. Langer, MD

Director, Thoracic Oncology

Professor of Medicine at the Hospital of the University of Pennsylvania

Professor C-E

Taine T.V. Pechet, MD

Chief of Surgery, Penn Presbyterian Medical Center

Associate Professor of Clinical Surgery

Associate Professor AC

Sunil Singhal, MD

Director, Thoracic Surgery Research Laboratory

William Maul Measey Associate Professor in Surgical Research

Associate Professor

Anil Vachani, MD

Director of Clinical Research, Section of Interventional Pulmonary and Thoracic Oncology

Associate Professor of Medicine at the Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center

Associate Professor C-E

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