PET Probe-Guided Surgery in Patients with Breast Cancer: Proposal for a Methodological Approach

Abstract

Nuclear medicine has an essential and increasing role in the management of patients with breast cancer. Sentinel node detection has achieved reliability and, at present, it has an important place in clinical management. Even in the era of gene-expression profiling, nodal status remains one of the primary prognostic discriminants in patients with breast cancer, and is of great value as an independent predictor of distant disease development. Although several institutional case series have differed in patient selection, follow-up, type of surgery, and adjuvant therapies, they have consistently shown that the percentage of positive lymph nodes is a significant indicator of survival in women with axillary metastases on final pathology (1-5). The American Society of Clinical Oncology convened an Update Committee of experts to provide evidence-based recommendations to practicing oncologists, surgeons, and radiation therapy clinicians on the use of sentinel node biopsy (SNB) for patients with early-stage breast cancer (6). The need to perform axillary lymph node dissection (ALND) when SNB is positive and administration of contemporary adjuvant treatment including radiotherapy, chemotherapy, and hormonal therapy has been questioned in recent years. On the other hand, ongoing trials are testing whether node-positive patients can be spared chemotherapy, as qualifying indications increasingly rely on breast cancer biology for decision-making regarding adjuvant systemic treatment (7). In summary, sentinel node surgery represents the next major step in reducing the extent of surgical procedures, but despite the revolution of quality-conserving care, recent data collection and analyses of anatomical techniques suggest that exact lymphatic drainage of the breast is debatable (8). Different lymphatic patterns may help explain some important unresolved clinical problems, including different detection rates between studies and high false-negative rates of about 10% in multicenter randomized controlled trials (9). Further anatomical investigation and knowledge of the exact sentinel lymphatic channels will provide more information about patterns of breast cancer in order to improve surgical strategy, locoregional recurrence, and survival.

Evaluation of Concordance Between Histopathological, Radiological and Biomolecular Variables in Breast Cancer Neoadjuvant Treatment

“…Therefore, histological examination of the biopsies' sample at the end of NAC is essential before subsequent surgical treatment. In our opinion, either molecular or nuclear dedicated breast imaging could improve the sensibility and complete surgical resection of any residual tumors (39)(40)(41). Additionally, EFS and OS indices have been calculated and proven to be greater, as also reported in literature, in those patients who obtained pCR.…”

Impact of Awake Breast Cancer Surgery on Postoperative Lymphocyte Responses

“…Application of the same protocols in breast surgery might allow length of stay and opioid use to be reduced, with an even faster prompt resumption of common activities of daily life and freeing-up of hospital beds (32)(33). The breast cancer surgery ACOSOG Z0011 (Alliance) randomized clinical trial demonstrated the non inferiority of SLNB alone compared to axillary node dissection in patients with SLNB metastases treated with BCS, increasing the number of procedures that can be completed under local anesthesia alone (37)(38)(39).…”

Emerging Intraoperative Imaging Modalities to Improve Surgical Precision

“…Nuclear imaging modalities, single photon emission computed tomography (SPECT) and positron emission tomography [64], are non-invasive whole-body imaging technologies, valued for their sensitivity and limitless depth of penetration. 2D scintigraphy and 3D SPECT employ nuclides like Technetium-99m ( 99m Tc, t1/2 6 h) and Indium-111 ( 111 In, t1/2 2.8 days), that emit gamma photons of varying energies, which are then detected by gamma cameras.…”

“…Though RGS using PET tracers is not as well established, it has been evaluated in the clinic to guide resection, assess lymph node metastasis in a range of malignancies, and locoregional nodal status for initial staging of breast cancer [64,70]. Most of these studies have used 18 F-FDG, typically administered a few hours prior to surgery.…”

“…A dedicated PET high-energy gamma probe, designed specifically to detect the keV photons, has been evaluated in numerous clinical studies. However, a recent study by Orsaria et al concluded that hand-held PET gamma probeguided surgery with 18 F-FDG performed poorly in evaluating axillary lymph nodes due to high background gamma levels from local and distant parts of the body [64]. PET tracers have also been evaluated with a hand-held positron detection probe, although the short range of beta emissions (typically 2-3 mm in soft tissue for 18 F-labeled agents) precludes the detection of deep-seated lesions, detection of beta emissions provides greater specificity (higher TBRs) in the localization of superficial tumor deposits.…”