Observational study into specific in vivo human discrimination between benign and malignant tissue using a combination of Diffuse Reflectance and Fluorescence spectroscopy

Early detection of a novel malignancy, preferably before differentiation into
metastatic disease, is essential for optimal chance of curative therapy.
Before an optimal therapeutic plan can be decided on, it is fundamental to
describe the anatomical extent as well as the histological origin of the tumor.
Histopathology is considered the golden standard for malignancy diagnosis.
Samples of suspected tissue are generally acquired by cytological or
histological biopsy. Delay of diagnosis, and thus of subsequent initiation of
therapy, is generally due to indeterminate result of cytological or
histological biopsy. Successful biopsy accuracy ranges from 68% to 92%.
Moreover, after malignancy diagnosis one possible treatment procedures include
percutaneous radio frequent ablation (RFA). Precise positioning of both biopsy
needle and RFA needle is essential for effective diagnosis or treatment. During
these procedures, the medical physician is mainly dependent on current
conventional imaging techniques, such as ultrasound and computed tomography for
this positioning. However, visualization of relevant structures can be limited
due to thresholds in contrast and image resolution.
In recent years promising advances in cancer treatment imaging have been made
with optical spectroscopy. By illuminating specific tissue with a selected
light spectrum and subsequent analysis of the characteristic scattering,
absorption and luminescence patterns, it is possible to obtain a *chemical
fingerprint* of the tissue and discriminate between benign and malignant
tissue. This novel analysis have been proven to be more sensitive in tissue
discrimination than conventional imaging techniques. Incorporation of optical
spectroscopy technology into current diagnostic or therapeutic tools, e.g.
biopsy needle, could improve invasive procedure localisation and thus improve
procedure accuracy and outcome.
We have developed a optical spectroscopy system for measurement of tissue
characteristics.
The concept has been tested with a prototype on excised human tissue. In this
ex-vivo study between benign and malignant tissue of breast, lung and liver
tissue, we have demonstrated discrimination sensitivity and specificity to be
>94% within patient analysis. Comparison studies in the literature have
demonstrated maximum sensitivity and specificity percentages to be 83%.
We conclude from our studies that we can confirm the position of the needle tip
in the tissues that are relevant for the medical physician during a needle
intervention. Thus, we can discriminate tumor tissue from normal tissue with
sufficient accuracy for clinical application.

Aim of this study is to confirm the results from ex vivo research in humans in
a clinical setting. The objective is to perform optical spectroscopy
measurements during surgical procedures in vivo, involving resection of either
breast, liver or lung tissue due to proven malignancy.
Optical spectroscopy measurement of the tissues will compared to
histopathological analysis as golden standard.

The hypothesis that will be tested is:

With optical spectroscopy, it is possible to discriminate between benign and
malignant tissue in vivo in organs like breast, lung and liver.

With this study we aim to make an important step forward towards the
incorporation of optical spectroscopy in current medical instruments improving
medical diagnosis and therapy of cancer.

The study is designed as an observational study.

Patients eligible for inclusion into the study are patients who are already
admitted to The Netherlands Cancer Institute (NKI-AvL) for elective resection
of lesions in breast, liver or lung.
Measurements will only be performed in the operation theatre under full
anaesthesia during elective surgery of a proven malignancy or benign
fibroadenoma. The optical measurements will be performed in tissue that will be
resected or ablated (in case of patients undergoing an RFA-procedure for
colorectal liver metastases).

Targeted lesions of the breast will involve invasive carcinoma as well as
carcinoma in situ lesions. Both patients that will be subjected for a total
resection and partial resection of the breast for the malignant lesion will be
included. Furthermore, patients who will be subjected to a local excision for a
benign fibroadenoma will be included.
Targeted lesions of the liver and lung will involve tumours requiring partial
resection by a surgical procedure or an ablation in patients undergoing an
RFA-procedure for colorectal liver metastases.

The surgeon responsible for the operation will identify the resection margins
of the targeted tissue specimen. By ultrasound guidance an 14G guidance canula
will be inserted into this tissue. Through this canula the optical needle,
biopsy apparatus and twist markers will be introduced into the tissue for
spectroscopy measurement procedure.
A maximum total of 4 measurements including benign and malignant tissue will be
performed on each patient within the tissue that will be resected.
Subsequently, two histological biopsies will be taken of the tissue, one of
normal tissue and one of malignant tissue..
In patients with colorectal liver metastases undergoing an RFA-procedure, the
same spectroscopy measurements will be performed en before, during and after
ablation biopsies of the liver metastases will be taken at the measurement
locations for histopathologic analysis. Following the ablation therapy some
twistmarkers will be inserted at the egde of the ablation zone for
post-operative follow-up.
The anticipated total time for optical spectroscopy measurements,biopsies and
insertion of twist marker is about 10 minutes.

Tissue biopsies will be analysed by the pathologist via standardized protocol.
Histopathological analysis of the optical measurement locations will be
provided for comparison with optical analysis

Because of the nature of this test, we do not expect any adverse events to
occur that are related to technology of the optical spectroscopy hardware.
Measurements shall be performed under full anesthesia and monitoring during
scheduled operations. In patients undergoing RFA of liver metastases in whom a
twistmarker will be left in place to mark the edge of the RFA zone, we do not
expect risk or burden since these twiskmarkers are produced for tissue
marking.
Collected data will not be provided to surgical physicians and the planned
surgical procedure will not be influenced by the optical measurements.