Frequent optical imaging during breast cancer neoadjuvant chemotherapy reveals dynamic tumor physiology in an individual patient.

Rationale and objectivesImaging 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 methodsDiffuse 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 x 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period.ResultsA composite index, the Tissue Optical Index (TOI), showed a significant ( approximately 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.ConclusionThis case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy

Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy

Diffuse optical spectroscopic imaging (DOSI) non-invasively and quantitatively measures tissue haemoglobin, water and lipid. Pilot studies in small groups of patients demonstrate that DOSI may be useful for longitudinal monitoring and predicting breast cancer neoadjuvant chemotherapy pathological response. This study evaluates the performance of a bedside DOSI platform in 34 breast cancer patients followed for several months. DOSI optical endpoints obtained at multiple timepoints are compared with final pathological response. Thirty-six stage II/III breast cancers (34 patients) were measured in vivo with DOSI prior to, in the middle of and after the completion of pre-surgical neoadjuvant chemotherapy. Cancer therapies ranged from standard anthracyclines to targeted therapies. Changes in DOSI-measured parameters at each timepoint were compared against final surgical pathology. Absolute changes in the tumour-to-normal (T/N) ratio of tissue deoxyhaemoglobin concentration (ctHHb) and relative changes in the T/N ratio of a tissue optical index (TOI) were most sensitive and correlate to pathological response. Changes in ctHHb and TOI were significantly different between tumours that achieved pathological complete response (pCR) versus non-pCR. By therapy midpoint, mean TOI-T/N changes were 47±8 versus 20±5 per cent for pCR versus non-pCR subjects, respectively (Z=0.011). Changes in ctHHb and TOI scaled significantly with the degree of pathological response (non-, partial and complete). DOSI measurements of TOI separated pCR from non-pCR by therapy midpoint regardless of drug or dosing strategy. This approach is well suited to monitoring breast tumour response and may provide feedback for optimizing therapeutic outcomes and minimizing side-effects

Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy.

Diffuse optical spectroscopic imaging (DOSI) non-invasively and quantitatively measures tissue haemoglobin, water and lipid. Pilot studies in small groups of patients demonstrate that DOSI may be useful for longitudinal monitoring and predicting breast cancer neoadjuvant chemotherapy pathological response. This study evaluates the performance of a bedside DOSI platform in 34 breast cancer patients followed for several months. DOSI optical endpoints obtained at multiple timepoints are compared with final pathological response. Thirty-six stage II/III breast cancers (34 patients) were measured in vivo with DOSI prior to, in the middle of and after the completion of pre-surgical neoadjuvant chemotherapy. Cancer therapies ranged from standard anthracyclines to targeted therapies. Changes in DOSI-measured parameters at each timepoint were compared against final surgical pathology. Absolute changes in the tumour-to-normal (T/N) ratio of tissue deoxyhaemoglobin concentration (ctHHb) and relative changes in the T/N ratio of a tissue optical index (TOI) were most sensitive and correlate to pathological response. Changes in ctHHb and TOI were significantly different between tumours that achieved pathological complete response (pCR) versus non-pCR. By therapy midpoint, mean TOI-T/N changes were 47±8 versus 20±5 per cent for pCR versus non-pCR subjects, respectively (Z=0.011). Changes in ctHHb and TOI scaled significantly with the degree of pathological response (non-, partial and complete). DOSI measurements of TOI separated pCR from non-pCR by therapy midpoint regardless of drug or dosing strategy. This approach is well suited to monitoring breast tumour response and may provide feedback for optimizing therapeutic outcomes and minimizing side-effects

Urine Protein/Creatinine Ratios during Labor: A Prospective Observational Study

<div><p>Purpose</p><p>To evaluate the utility of urine protein/creatinine ratio (uPCR) measurements among healthy parturients at term we performed a prospective cohort study at a community teaching hospital.</p><p>Methods</p><p>Serial urine samples were collected. Ninety-three women contributed 284 urine samples. uPCRs were determined. Multiple imputation and paired sampled analysis was performed when appropriate.</p><p>Results</p><p>Two-thirds (63/93) of women had at least one measured uPCR ≥ 0.3. One-third (31/93) had a uPCR ≥ 0.3 at admission, including 39.1% (9/23) of women not in labor. Median (IQR) uPCRs increased during labor and after delivery: latent phase/no labor, 0.15 (0.06–0.32); active phase, 0.29 (0.10–0.58); early postpartum, 0.45 (0.18–1.36) (all p < 0.04). Median uPCRs were significantly < 0.3 in the latent phase and significantly > 0.3 in the immediate postpartum period (p < 0.01). Women who labored before cesarean delivery had the highest early postpartum uPCRs: median (IQR) 1.16 (0.39–1.80). A negative urine dipstick protein result did not exclude uPCR ≥ 0.3. uPCRs were similar when compared by method of urine collection.</p><p>Conclusion</p><p>uPCR ≥ 0.3 is common among healthy women with uncomplicated pregnancies at term. uPCR increases during labor and is not a reliable measure of pathologic proteinuria at term or during the peripartum period.</p></div

Comparison of women with or without elevated urinary protein/creatinine ratio (uPCR).

<p>Comparison of women with or without elevated urinary protein/creatinine ratio (uPCR).</p

Urinary protein/creatinine ratio (uPCR) by urine dipstick protein result.

<p>Urinary protein/creatinine ratio (uPCR) by urine dipstick protein result.</p

Box plots of urine protein/creatinine ratio (uPCR) measurements by phase of labor at the time of collection and subsequent delivery outcome.

<p>uPCR measurements from samples collected before and after delivery among women who had a scheduled cesarean delivery without labor (<i>top left</i>), all laboring women (<i>top right</i>), laboring women who delivered vaginally (<i>bottom left</i>), and laboring women who subsequently delivered by cesarean (<i>bottom right</i>) are shown. The horizontal line on each graph represents the threshold uPCR value of 0.3. When the distribution of observed uPCR values is significantly different than the threshold value of 0.3, the p-value (Mann-Whitney u test) is shown.</p

Demographic characteristics and clinical information for the study population (n = 93).

<p>Demographic characteristics and clinical information for the study population (n = 93).</p

Box plots of urine protein/creatinine ratio (uPCR) measurements by urine protein dipstick result.

<p>The horizontal line on each graph represents the threshold uPCR value of 0.3. When the distribution of observed uPCR values is significantly different than the threshold value of 0.3, the p-value (Mann-Whitney u test) is shown. Three uPCR outlier values (4.9, 6.1, and 8.9 in the Negative, 1+, and 2+ groups, respectively) are not shown.</p

Urine protein/creatinine ratio (uPCR) measurements in all 284 urine samples from 93 women plotted against the timing of the sample collection relative to delivery time.

<p>The phase of labor at the time of sample collection is shown for each individual sample by one of four different colors. The horizontal line represents the threshold uPCR value of 0.3.</p