High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing ...resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e-11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e-14). Extending the radiomics approach to high-dimensional optical data-termed "optomics" in this study-offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available.
Background
Roughly 23% of breast conserving surgery (BCS) patients undergo a second re-excision procedure due to pathologically positive surgical margins. We investigated the feasibility and ...potential value of micro-Computed Tomography (micro-CT) as a surgical margin guidance tool during BCS.
Methods
A cohort of 32 BCS specimens was prospectively imaged with a pre-clinical micro-CT system upon arrival in the surgical pathology laboratory. Reconstructed micro-CT scans were evaluated retrospectively by an experienced breast radiologist, who provided binary determinations whether lesions extended to the specimen margin. These readings were then compared to the final pathological diagnosis and to 2D specimen radiography readings.
Results
Of the 32 specimens imaged, 28 had malignant and four had benign pathological diagnoses. Overall five (four malignant, one benign) of the 32 specimens had lesion tissue extending to the margin. For all 32 specimens, micro-CT reconstructions were calculated (< 4 min. acquisition + reconstruction time) and each specimen was volumetrically analyzed by a radiologist. Of the 28 malignant specimen readings, 18 matched the final pathological diagnosis 64%, 95 CI (47%–81%), with a negative predictive value of 89% 95 CI (74%–96%). Micro-CT readings revealed changes in the tumor location and margin status as compared to single-projection radiography readings.
Conclusions
Micro-CT scanning of BCS specimens enabled margin status assessment over the entirety of the surgical surface in a clinically relevant time frame, provided additional spatial information over single-projection radiography, and may be a potentially useful BCS guidance tool.
Background
Breast-conserving surgery (BCS) is an integral component of early-stage breast cancer treatment, but costly reexcision procedures are common due to the high prevalence of cancer-positive ...margins on primary resections. A need exists to develop and evaluate improved methods of margin assessment to detect positive margins intraoperatively.
Methods
A prospective trial was conducted through which micro-computed tomography (micro-CT) with radiological interpretation by three independent readers was evaluated for BCS margin assessment. Results were compared to standard-of-care intraoperative margin assessment (i.e., specimen palpation and radiography abbreviated SIA) for detecting cancer-positive margins.
Results
Six hundred margins from 100 patients were analyzed. Twenty-one margins in 14 patients were pathologically positive. On analysis at the specimen-level, SIA yielded a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 42.9%, 76.7%, 23.1%, and 89.2%, respectively. SIA correctly identified six of 14 margin-positive cases with a 23.5% false positive rate (FPR). Micro-CT readers achieved sensitivity, specificity, PPV, and NPV ranges of 35.7–50.0%, 55.8–68.6%, 15.6–15.8%, and 86.8–87.3%, respectively. Micro-CT readers correctly identified five to seven of 14 margin-positive cases with an FPR range of 31.4–44.2%. If micro-CT scanning had been combined with SIA, up to three additional margin-positive specimens would have been identified.
Discussion
Micro-CT identified a similar proportion of margin-positive cases as standard specimen palpation and radiography, but due to difficulty distinguishing between radiodense fibroglandular tissue and cancer, resulted in a higher proportion of false positive margin assessments.
Introduction:
Tumor hypoxia confers both a poor prognosis and increased resistance to oncologic therapies, and therefore, hypoxia modification with reliable oxygen profiling during anticancer ...treatment is desirable. The OxyChip is an implantable oxygen sensor that can detect tumor oxygen levels using electron paramagnetic resonance (EPR) oximetry. We report initial safety and feasibility outcomes after OxyChip implantation in a first-in-humans clinical trial (NCT02706197,
www.clinicaltrials.gov
).
Materials and Methods:
Twenty-four patients were enrolled. Eligible patients had a tumor ≤ 3 cm from the skin surface with planned surgical resection as part of standard-of-care therapy. Most patients had a squamous cell carcinoma of the skin (33%) or a breast malignancy (33%). After an initial cohort of six patients who received surgery alone, eligibility was expanded to patients receiving either chemotherapy or radiotherapy prior to surgical resection. The OxyChip was implanted into the tumor using an 18-G needle; a subset of patients had ultrasound-guided implantation. Electron paramagnetic resonance oximetry was carried out using a custom-built clinical EPR scanner. Patients were evaluated for associated toxicity using the Common Terminology Criteria for Adverse Events (CTCAE); evaluations started immediately after OxyChip placement, occurred during every EPR oximetry measurement, and continued periodically after removal. The OxyChip was removed during standard-of-care surgery, and pathologic analysis of the tissue surrounding the OxyChip was performed.
Results:
Eighteen patients received surgery alone, while five underwent chemotherapy and one underwent radiotherapy prior to surgery. No unanticipated serious adverse device events occurred. The maximum severity of any adverse event as graded by the CTCAE was 1 (least severe), and all were related to events typically associated with implantation. After surgical resection, 45% of the patients had no histopathologic findings specifically associated with the OxyChip. All tissue pathology was “anticipated” excepting a patient with greater than expected inflammatory findings, which was assessed to be related to the tumor as opposed to the OxyChip.
Conclusion:
This report of the first-in-humans trial of OxyChip implantation and EPR oximetry demonstrated no significant clinical pathology or unanticipated serious adverse device events. Use of the OxyChip in the clinic was thus safe and feasible.
Background
Wire-localized excision of non-palpable breast cancer is imprecise, resulting in positive margins 15–35% of the time.
Methods
Women with a confirmed diagnosis of non-palpable invasive ...breast cancer (IBC) or ductal carcinoma in situ (DCIS) were randomized to a new technique using preoperative supine magnetic resonance imaging (MRI) with intraoperative optical scanning and tracking (MRI group) or wire-localized (WL group) partial mastectomy. The main outcome measure was the positive margin rate.
Results
In this study, 138 patients were randomly assigned. Sixty-six percent had IBC and DCIS, 22% had IBC, and 12% had DCIS. There were no differences in patient or tumor characteristics between the groups. The proportion of patients with positive margins in the MRI-guided surgery group was half that observed in the WL group (12 vs. 23%;
p
= 0.08). The specimen volumes in the MRI and WL groups did not differ significantly (74 ± 33.9 mL vs. 69.8 ± 25.1 mL;
p
= 0.45). The pathologic tumor diameters were underestimated by 2 cm or more in 4% of the cases by MRI and in 9% of the cases by mammography. Positive margins were observed in 68% and 58% of the cases underestimated by 2 cm or more using MRI and mammography, respectively, and in 15% and 14% of the cases not underestimated using MRI and mammography, respectively.
Conclusions
A novel system using supine MRI images co-registered with intraoperative optical scanning and tracking enabled tumors to be resected with a trend toward a lower positive margin rate compared with wire-localized partial mastectomy. Margin positivity was more likely when imaging underestimated pathologic tumor size.
The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen ...assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing.
Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO
) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry.
Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4-128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO
values were variable with overall median 15.7 mmHg (range 0.6-73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO
was 31.8 mmHg (range 1.5-144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation.
Measurement of baseline pO
and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.
Background
Wire-localized excision of nonpalpable breast cancer is imprecise, resulting in positive margins 25–30% of the time.
Methods
Patients underwent preoperative supine magnetic resonance ...imaging (MRI). A radiologist outlined the tumor edges on consecutive images, creating a three-dimensional (3D) view of its location. Using 3D printing, a bra-like plastic form (the Breast Cancer Locator BCL) was fabricated, with features that allowed a surgeon to (1) mark the edges of the tumor on the breast surface; (2) inject blue dye into the breast 1 cm from the tumor edges; and (3) place a wire in the tumor at the time of surgery.
Results
Nineteen patients with palpable cancers underwent partial mastectomy after placement of surgical cues using patient-specific BCLs. The cues were in place in <5 min and no adverse events occurred. The BCL accurately localized 18/19 cancers. In the 18 accurately localized cases, all 68 blue-dye injections were outside of the tumor edges. Median distance from the blue-dye center to the pathologic tumor edge was 1.4 cm, while distance from the blue dye to the tumor edge was <5 mm in 4% of injections, 0.5–2.0 cm in 72% of injections, and >2 cm in 24% of injections. Median distance from the tumor center to the BCL-localized wire and to the clip placed at the time of diagnosis was similar (0.49 vs. 0.73 cm) on specimen mammograms.
Conclusions
Information on breast cancer location and shape derived from a supine MRI can be transferred safely and accurately to patients in the operating room using a 3D-printed form.
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