Assessment of safety, sensitivity, and Accuracy of Cancer Diagnostic Probe (CDP) for the detection of cancer cell during Breast Cancer Surgery - A Multicenter collaborative Pilot Project.

Full Title of the Study: Assessment of safety, sensitivity, and Accuracy of Cancer Diagnostic Probe (CDP) for the detection of cancer cell during Breast Cancer Surgery - A Multicenter collaborative Pilot Project.

Objectives of the study :

·        Primary Objectives:

1.      To assess the safety, sensitivity, and accuracy of Cancer Diagnostic Probe (CDP) for breast cancer detection during Breast cancer surgery.

·        Secondary Objectives:

1.   To detect cancer cell at the margin of post lumpectomy cavity wall

2.   To compare the sensitivity of CDP and Frozen section in breast cancer surgery

3.  To compare the sensitivity of CDP and Frozen section in detecting Cancer cells in Sentinel Lymph Node.

Justification for conduct of this study

Breast cancer (BC) is the most prevalent malignant solid tumor among women worldwide, and Breast Conserving Surgery (BCS) has been proven as the best surgery method for early-stage BC patients in clinical studies. Remained positive margins is still a moot point with drastic impact on risk of cancer recurrence. Residue of tumor cells in cavity side may induce dangerous challenge as they are in interaction with accumulated cytokines (in surgical bed fluid).  Therefore, it is imperative to develop effective strategies to minimize involved margins and ensure optimal results for patients.  Up to 20 % of the margins may remain positive despite utilizing conventional intra-operative methods. In addition, the frozen section is a time-consuming, expensive and labor-intensive process, adding the risk of false negatives (6-20%) owing to technical limitations such as incomplete fixation of pathology samples. Bioelectronic science has emerged as a novel strategy in cancer research, allowing discrimination between cancerous and non-cancerous cells and tissues, broadening the horizon of cancer research. A recently developed technique, the Cancer diagnostic probe (CDP) (granted USA patents: US 11,179,076 B2, US 10,786,188 B1, US 11,179,077 B2, US 11,181,499 B2, US 11,806,140 B2), has been known as another complementary electrical method, which shed new lights in real-time diagnosing the presence of pre-cancerous and cancerous cells in cavity margins of breast tumors via the assistance of electrical probing on biochemical metabolism of the live cells in the margins.This highlights the impact of CDP as an innovative intraoperative technique to evaluate cavity side margins effectively.

Methodology:

Study site and Design:

·        This is a prospective pilot study, and the study will be carried out in the Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.

·        A total of 50 patients confirming the diagnosis of breast cancer.

Patient Recruitment and Sample Collection:

·        Ethical approval for the study will be taken from the Institute Ethics Committee, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

·        Each patient will be enrolled after approval from EIC with their written informed consent.

·        For the study, prospectively selected n=50 patients with tumor will be recruited, irrespective of their treatment status. CDP will be applied on tumor and normal cells during surgery (MRM/ Breast Conserving Surgery). Hence the tumor cell, normal cells, cavity margins and sentinel LN will be assessed by CDP. The results will be observed accordingly and further correlated with histopathology report.

Inclusion and Exclusion Criteria:

The following inclusion criteria will be considered for the study

CDP can be used for patients of all ages and genders with breast tumor disease who are candidates for breast-conserving surgery in adjuvant/non-neoadjuvant cases.

Patients with the following will be excluded from the study:

1. Patients with non-palpable tumor

2. Patients exhibiting post-NACT complete response

All patients diagnosed with breast cancer, which were candidates for breast-conserving surgery. All the patients will be informed about the process and sign the consent before the surgery. The patient’s gender, age, and surgical history, and adjuvant or neoadjuvant chemotherapy are not effective parameters for the patient’s recruitment.

The workflow of the proposed study is as follows

This is a multicenter pilot study for evaluating the safety, sensitivity, and Accuracy of a Cancer Diagnostic Probe (CDP) for the detection of cancer cells in-vivo during Breast Cancer Surgery and subsequently, results obtained by the CDP probe will be compared with gold standard histopathology of the same cavity lesion recorded by CDP. During breast-conserving surgery, the surgeon will apply the CDP on cavity side margins (CDP electrodes should be inserted up to 4 mm) after resection of the tumor (the resected tumor will be sent for a frozen section and then permanent pathology (pathological evaluation on tumor side margins)). Surgeons will not be biased toward the CDP scoring results. So, all negatively and positively scored lesions will be re-excised for pathological evaluation. The size of each excised lesion will be about 1×1×1 cm3. These samples are called as “CDP Samples”. The required time for checking all of the margins by CDP is about 10 min.

CDP Samples will be sent for permanent pathology to be evaluated pathologically as the gold standard. At this stage, the pathologist must be blinded to the CDP results. In this manner, we have no bias during the trial and the score of CDP does not affect the decision of the surgeon and pathologist while all of the data will be compared with an accepted gold standard. Independently the tumor (the resected tumor) will be sent for a frozen section and then permanent pathology (pathological evaluation on tumor side margins). Finally, after the collection of all lesions in fixed block samples (cavity side lesions recorded by CDP), the lesions will be sent for H&E slide sectioning, and independent and blind pathologists will evaluate and declare their diagnosis on the cavity lesions. Finally, the epidemiologist of the project will integrate all the data and report two tables. The first matching table of CDP scores by H&E of cavity margins (as sensitivity and accuracy), the second comparative table between CDP score, the frozen score of the tumor side and the permanent score of the tumor side all with the permanent score of the cavity side (gold merit) in second table the sensitivity and accuracy of frozen and permanent of tumor side will also be compared with the pathologic state of cavity side margins. Also, the cross table and ROC curve will be presented to compare the results.