Rationale and Objectives
Imaging tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about tumor response dynamics may be missed. In addition, current clinical standards are based on determining tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier-to-access bedside approach that can be used for frequent, functional assessment of dynamic tumor physiology in individual patients.
Materials and Methods
Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial tumor size 60 × 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period.
Results
A composite index, the Tissue Optical Index (TOI), showed a significant (∼50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic tumor physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery.
Conclusion
This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy.
Presurgical neoadjuvant chemotherapy (NAC) has an increasingly important role in breast cancer patient care and drug development . Also referred to as “preoperative systemic therapy,” NAC has become standard of care for locally advanced and inflammatory breast cancer . In this setting, chemotherapy is administered before surgery to improve breast tissue conservation by reducing tumor size . Additional important benefits compared to adjuvant chemotherapy include the ability to directly assess an individual’s sensitivity to specific drugs, and initiating treatment of possible nodes and metastases before surgery.
Imaging individual tumor response can provide sufficient information for oncologists to alter therapeutics with a goal of improving overall survival, decreasing cancer recurrence, and minimizing exposure to ineffective drugs. Several groups are developing advanced imaging techniques for monitoring the effects of neoadjuvant chemotherapy, using for example magnetic resonance imaging (MRI) and spectroscopy (MRS), and positron emission tomography (PET) . These studies provide compelling evidence that functional imaging can be used to monitor and perhaps even predict therapeutic outcome . However, it is unclear what are the most sensitive and informative imaging end points and how often they should be assessed.
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Materials and methods
Instrumentation
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Measured Information Content
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DOSI Measurement Technique
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Image Analysis
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Patient Selection
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Measurement and Treatment Schedules
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Results
Baseline Tumor NIR Absorption Spectra
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Table 1
Tumor Functional Properties Measured by DOSI before Chemotherapy
ctO 2 Hb (μM) ctHHb (μM) ctH 2 O (%) Lipid (%) TOI Tumor 15.0 ± 1.0 9.0 ± 1.2 40.7 ± 5.9 51.4 ± 4.2 7.7 ± 2.8 Normal 13.0 ± 2.2 6.0 ± 1.1 23.0 ± 6.3 71.5 ± 9.5 2.2 ± 1.1
DOSI, Diffuse Optical Spectroscopic Imaging; ctO 2 Hb, tissue concentration of oxy-hemoglobin; ctHHb, tissue concentration of deoxy-hemoglobin; ctH 2 O, tissue concentration of water; TOI, tissue optical index.
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Initial A/C Chemotherapy Stage
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Bevacizumab Therapy Stage
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Entire Therapy Sequence
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Discussion
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Conclusion
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Acknowledgments
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