Does Scalp Cooling Have the Same Efficacy in Black Patients Receiving Chemotherapy for Breast Cancer?

LESSONS LEARNED: Despite U.S. Food and Drug Administration approval to reduce alopecia, data on efficacy of scalp cooling in Black patients with cancer are limited by lack of minority representation in prior clinical trials. Scalp cooling devices may have less efficacy in Black patients; additional studies are required to explore the possible causes for this, including hair texture and cap design. BACKGROUND: The Paxman scalp cooling (SC) device is U.S. Food and Drug Administration (FDA)-approved for prevention of chemotherapy-induced alopecia. Studies report 50%-80% success rates and high patient satisfaction, yet there have been no studies of SC in Black patients. We conducted a phase II feasibility study of Paxman SC with a planned enrollment of 30 Black patients receiving chemotherapy for stage I-III breast cancer. METHODS: Black patients who planned to receive at least four cycles of chemotherapy with non-anthracycline (NAC) or anthracycline (AC) regimens were eligible. Alopecia was assessed by trained oncology providers using the modified Dean scale (MDS) prior to each chemotherapy session. Distress related to alopecia was measured by the Chemotherapy Alopecia Distress Scale (CADS). RESULTS: Fifteen patients enrolled in the intervention before the study was closed early because of lack of efficacy. Median MDS and CADS increased after SC, suggesting increased hair loss (p < .001) and alopecia distress (p = .04). Only one participant was successful in preventing significant hair loss; the majority stopped SC before chemotherapy completion because of grade 3 alopecia (>50% hair loss). CONCLUSION: SC may not be efficacious in preventing alopecia in Black women. Differences in hair thickness, hair volume, and limitations of cooling cap design are possible contributing factors.

A Limb Hypothermia Wearable for Chemotherapy-Induced Peripheral Neuropathy: A Mixed-Methods Approach in Medical Product Development.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common dose-limiting side-effect of taxane-based chemotherapy, causing progressive and often irreversible pain/sensitivity in the hands and feet. Prevention/treatments for CIPN are not well-developed and urgently needed. Limb cryocompression during chemotherapy has demonstrated promising early data of preventing/reducing CIPN severity. Currently there are no medical devices available that are dedicated to the specific requirements of CIPN prevention. As part of our ongoing development of a dedicated CIPN-prevention limb cryocompression system, this study documents the design & development of the wearable arm wrap, a central component of the system, from initial concept to a trial-ready prototype. A collaborative and multidisciplinary approach was adopted to address the complex and high-risk nature of this SME (Small Medium Enterprise)-centered medical device design & development process. The complementary collaboration unites multidisciplinary expertise spanning the scope of the project. Alongside the clinical, academic, and design & development expertise, the integration of commercial expertise is imperative to promote the market viability, and ultimate success, of the development. As the global leading experts in scalp cooling specializing in the prevention of chemotherapy-induced alopecia, UK-based SME Paxman Coolers Ltd is optimally positioned to support the commercial and regulatory dimensions. Development and adoption of a novel mixed-methodology (HudPAX) facilitated the integration of evidence-based and user-centered techniques to optimize the design & development approach and ensure integration of all critical design inputs. Alpha prototypes were designed through evidence-based approaches, with data from existing clinical trials utilized to determine the preliminary design inputs, alongside 3D ergonomic data. Investigations utilized computer-aided design, rapid prototyping, additive manufacturing, sketch modeling, and fast ideation. User-based approaches facilitated stakeholder-feedback through expert focus groups, informing further design & development and projecting the design into the next stage, Beta prototyping, for use in large-scale efficacy trials and upscaling manufacturing. This paper demonstrates a novel mixed-methods approach, which promotes cross-sector multidisciplinary collaboration, to address the complex multi-layered challenges posed by an early-stage medical device design & development process.

Experimental evidence for spatial stabilization of deep-turbulence-induced anisoplanatic blur.

We present field-experiment support for the feasibility of post-detection restoration when imaging through deep turbulence characterized by extreme anisoplanatism. Short-exposure images of point-like and minimally extended objects (MEOs) were collected, viewed through a 5.1-kilometer atmospheric path producing isoplanatic angles roughly 1/15th the camera diffraction-limited angular resolution. A correlation-based isoplanatic angle measurement technique is presented along with data verifying deep-turbulence conditions. In agreement with prior wave-optics simulations, the experiments demonstrate short-exposure images of MEOs retain a central lobe that is clearly narrower than the long-exposure counterpart, even in the presence of severe anisoplanatism. New simulations are presented to provide direct comparison with measurements of point-like and MEO image central lobe radius statistics.

Piston alignment for a segmented-aperture imaging system by using piston-sweep phasing.

This Letter presents a novel method for aligning the piston settings for a segmented-aperture imaging system. By sweeping the piston setting for a reference segment, a stack of images can be acquired that encodes information about the relative piston alignment for all segments in the system. We also demonstrate how a matched-filter processing method can be used to estimate the relative piston settings to align the imaging system at its full resolution.

Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer: The SCALP Randomized Clinical Trial.

Importance: Chemotherapy may induce alopecia. Although scalp cooling devices have been used to prevent this alopecia, efficacy has not been assessed in a randomized clinical trial. Objectives: To assess whether a scalp cooling device is effective at reducing chemotherapy-induced alopecia and to assess adverse treatment effects. Design, Setting, and Participants: Multicenter randomized clinical trial of women with breast cancer undergoing chemotherapy. Patients were enrolled from December 9, 2013, to September 30, 2016. One interim analysis was planned to allow the study to stop early for efficacy. Data reported are from the interim analysis. This study was conducted at 7 sites in the United States, and 182 women with breast cancer requiring chemotherapy were enrolled and randomized. Interventions: Participants were randomized to scalp cooling (n = 119) or control (n = 63). Scalp cooling was done using a scalp cooling device. Main Outcomes and Measures: The primary efficacy end points were successful hair preservation assessed using the Common Terminology Criteria for Adverse Events version 4.0 scale (grade 0 [no hair loss] or grade 1 [<50% hair loss not requiring a wig] were considered to have hair preservation) at the end of 4 cycles of chemotherapy by a clinician unaware of treatment assignment, and device safety. Secondary end points included wig use and scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Hospital Anxiety and Depression Scale, and a summary scale of the Body Image Scale. Results: At the time of the interim analysis, 142 participants were evaluable. The mean (SD) age of the patients was 52.6 (10.1) years; 36% (n = 51) received anthracycline-based chemotherapy and 64% (n = 91) received taxane-based chemotherapy. Successful hair preservation was found in 48 of 95 women with cooling (50.5%; 95% CI, 40.7%-60.4%) compared with 0 of 47 women in the control group (0%; 95% CI, 0%-7.6%) (success rate difference, 50.5%; 95% CI, 40.5%-60.6%). Because the 1-tailed P value from the Fisher exact test was <.001, which crossed the superiority boundary (P = .0061), the data and safety monitoring board recommended study termination on September 26, 2016. There were no statistically significant differences in changes in any of the scales of quality of life from baseline to chemotherapy cycle 4 among the scalp cooling and control groups. Only adverse events related to device use were collected; 54 adverse events were reported in the cooling group, all grades 1 and 2. There were no serious adverse device events. Conclusions and Relevance: Among women with stage I to II breast cancer receiving chemotherapy with a taxane, anthracycline, or both, those who underwent scalp cooling were significantly more likely to have less than 50% hair loss after the fourth chemotherapy cycle compared with those who received no scalp cooling. Further research is needed to assess longer-term efficacy and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01986140.

Spatial stabilization of deep-turbulence-induced anisoplanatic blur.

We explore the feasibility of post-detection restoration when imaging through deep turbulence characterized by extreme anisoplanatism. A wave-optics code was used to simulate relevant short-exposure point spread functions (PSFs) and their decorrelation as a function of point-source separation was computed. In addition, short-exposure images of minimally extended objects were simulated and shown to retain a central lobe that is clearly narrower than the long-exposure counterpart. This suggests that short-exposure image data are more informative than long-exposure data, even in the presence of extreme anisoplanatism. The implications of these findings for image restoration from a sequence of short-exposure images are discussed.

Silhouette estimation.

Silhouettes arise in a variety of imaging scenarios. Pristine silhouettes are often degraded via blurring, detector sampling, and detector noise. We present a maximum a posteriori estimator for the restoration of parameterized facial silhouettes. Extreme dealiasing and dramatic superresolution, well beyond the diffraction limit, are demonstrated through the use of strong prior knowledge.

Vector transmission matrix for the polarization behavior of light propagation in highly scattering media.

Recently the optical transmission matrix (TM) has been shown to be useful in controlling the propagation of light in highly scattering media. In this paper, we present the vector transmission matrix (VTM) which, unlike the TM, captures both the intensity and polarization transmission property of the scattering medium. We present an experimental technique for measuring the absolute values of the VTM elements which is in contrast to existing techniques whereby the TM elements are measured to within a scaling factor. The usefulness of the VTM is illustrated by showing that it can be used to both predict and control the magnitude of the complex polarization ratio of the light focused through the scattering medium. To the best of our knowledge, this is the first study to show the possibility of controlling the polarization of the light transmitted through highly scattering media.

Joint estimation of Stokes images and aberrations from phase-diverse polarimetric measurements.

The technique of phase diversity has been used in traditional incoherent imaging systems to jointly estimate an object and optical system aberrations. This paper extends the technique of phase diversity to polarimetric imaging systems. Specifically, we describe penalized-likelihood methods for jointly estimating Stokes images and optical system aberrations from measurements that contain phase diversity. Jointly estimating Stokes images and optical system aberrations involves a large parameter space. A closed-form expression for the estimate of the Stokes images in terms of the aberration parameters is derived and used in a formulation that reduces the dimensionality of the search space to the number of aberration parameters only. We compare the performance of the joint estimator under both quadratic and edge-preserving regularization; we also compare the performance of the reduced parameter search strategy to the full parameter search strategy under quadratic regularization. The joint estimator with edge-preserving regularization yields higher fidelity polarization estimates than with quadratic regularization. With the reduced parameter search strategy, accurate aberration estimates can be obtained without recourse to regularization "tuning."

Overcoming turbulence-induced space-variant blur by using phase-diverse speckle.

Space-variant blur occurs when imaging through volume turbulence over sufficiently large fields of view. Space-variant effects are particularly severe in horizontal-path imaging, slant-path (air-to-ground or ground-to-air) geometries, and ground-based imaging of low-elevation satellites or astronomical objects. In these geometries, the isoplanatic angle can be comparable to or even smaller than the diffraction-limited resolution angle. We report on a postdetection correction method that seeks to correct for the effects of space-variant aberrations, with the goal of reconstructing near-diffraction-limited imagery. Our approach has been to generalize the method of phase-diverse speckle (PDS) by using a physically motivated distributed-phase-screen model. Simulation results are presented that demonstrate the reconstruction of near-diffraction-limited imagery under both matched and mismatched model assumptions. In addition, we present evidence that PDS could be used as a beaconless wavefront sensor in a multiconjugate adaptive optics system when imaging extended scenes.