A survey of cancer patients, caregivers, and providers regarding familiarity, importance, and utilization of supportive and integrative oncology services.

PURPOSE: Supportive and integrative oncology services aim to improve the quality of life of cancer patients. This study characterizes the views of these services among cancer patients, caregivers, and providers at a comprehensive cancer center. METHODS: A cross-sectional survey was administered in 2017-2018. The survey asked about participants' familiarity, perceived importance, use, accessibility, and barriers to 19 supportive and integrative oncology services using a Likert scale. Data were analyzed using the Kruskal-Wallis test and a proportional odds regression model. RESULTS: A total of 976 surveys were obtained (604 patient surveys, 199 caregiver surveys, 173 provider surveys). Patients were mostly female (56.3%), ≥60 years old (59.4%), and Caucasian (66%). Providers were an even distribution of nurses, physicians, and advanced practice providers. Patients felt social work and nutrition services were the most familiar (36.4% and 34.8%) and the most important (46.3% and 54.5%). Caregivers were also most familiar with those two services, but felt that nutrition and learning resources were most important. Social work and nutrition were easiest to access and used the most by both patients and providers. There was a positive correlation between accessibility and perceived importance. Being unaware was the most common barrier identified by patients (38.4%), providers (67.1%), and caregivers (33.7%). CONCLUSION: Social work and nutrition services were most familiar to respondents, and also generally the most important, accessible, and utilized. Lack of awareness was the most common barrier cited and suggests that increased efforts to educate patients and providers about other services available are needed.

Interest and Willingness to Pay for Integrative Therapies of Patients With Cancer and Caregivers.

PURPOSE: Complementary and integrative medicine (CIM) services are more prevalent in cancer centers but continue to be underutilized by patients. This study examines perspectives from patients and caregivers about these services being offered at a comprehensive cancer center. METHODS: Patients and caregivers were surveyed about their familiarity, interest, and experience with five CIM therapies: acupuncture, massage, meditation, music therapy, and yoga. Respondents were asked about their interest in and/or paying for these services at baseline, when recommended by their medical team, and when offered in a clinical trial. Respondents were also asked about perceived barriers to accessing these services. Chi-squared tests were performed to explore associations between past experience, interest levels, and willingness to pay. RESULTS: A total of 576 surveys were obtained (464 patients and 112 caregivers). Most respondents identified as White or Caucasian (65.6%), female (57.2%), had been a patient for < 3 years (74.2%), had some college education (73.8%), and made > $40,000 in US dollars as their annual household income (69.1%). Respondents were most familiar with therapeutic massage (34.2%) and least familiar with acupuncture (20.0%). The average interest in these services increased from 53.3% to 64.1% when recommended by a medical professional. Respondents were most willing to pay $1-60 for therapeutic massage (62.3%) and least willing to pay for meditation (43.7%). The main barriers to accessing CIM services were cost (56.0%) and lack of knowledge (52.1%). CONCLUSION: Overall, a significant proportion of patients and caregivers were unfamiliar with these five integrative therapies. Increasing education, decreasing cost, and a recommendation by medical professionals would improve CIM usage.

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4.

To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose-response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4-PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl-2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl-2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl-1 was extensively cleaved in a dose- and caspase-dependent manner in Jurkat, but not in A431, cells exposed to Pc 4-PDT. Thus, the greater killing by Pc 4-PDT in Jurkat compared with A431 cells correlated with greater Bcl-2 photodamage and more strongly to the more extensive Mcl-1 degradation. Pc 4-PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T-cell-mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl-2 family proteins, especially Mcl-1, in the therapeutic response.

High-field magnetic resonance imaging of the response of human prostate cancer to Pc 4-based photodynamic therapy in an animal model.

INTRODUCTION: High-field magnetic resonance imaging (MRI) is an emerging technique that provides a powerful, non-invasive tool for in vivo studies of cancer therapy in animal models. Photodynamic therapy (PDT) is a relatively new treatment modality for prostate cancer, the second leading cause of cancer mortality in American males. The goal of this study was to evaluate the response of human prostate tumor cells growing as xenografts in athymic nude mice to Pc 4-sensitized PDT. MATERIALS AND METHODS: PC-3, a cell line derived from a human prostate malignant tumor, was injected intradermally on the back flanks of athymic nude mice. Two tumors were initiated on each mouse. One was treated and the other served as the control. A second-generation photosensitizing drug Pc 4 (0.6 mg/kg body weight) was delivered to each animal by tail vein injection 48 hours before laser illumination (672 nm, 100 mW/cm(2), 150 J/cm(2)). A dedicated high-field (9.4 T) small-animal MR scanner was used for image acquisitions. A multi-slice multi-echo (MSME) technique, permitting noninvasive in vivo assessment of potential therapeutic effects, was used to measure the T2 values and tumor volumes. Animals were scanned immediately before and after PDT and 24 hours after PDT. T2 values were computed and analyzed for the tumor regions. RESULTS: For the treated tumors, the T2 values significantly increased (P<0.002) 24 hours after PDT (68.2+/- 8.5 milliseconds), compared to the pre-PDT values (55.8+/-6.6 milliseconds). For the control tumors, there was no significant difference (P = 0.53) between the pre-PDT (52.5+/-6.1 milliseconds) and 24-hour post-PDT (54.3+/-6.4 milliseconds) values. Histologic analysis showed that PDT-treated tumors demonstrated necrosis and inflammation that was not seen in the control. DISCUSSION: Changes in tumor T2 values measured by multi-slice multi-echo MR imaging provide an assay that could be useful for clinical monitoring of photodynamic therapy of prostate tumors.

In Vivo Small Animal Imaging for Early Assessment of Therapeutic Efficacy of Photodynamic Therapy for Prostate Cancer.

We are developing in vivo small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center. In this study, we are developing magnetic resonance imaging (MRI) techniques that provide therapy monitoring and early assessment of tumor response to PDT. We generated human prostate cancer xenografts in athymic nude mice. For the imaging experiments, we used a high-field 9.4-T small animal MR scanner (Bruker Biospec). High-resolution MR images were acquired from the treated and control tumors pre- and post-PDT and 24 hr after PDT. We utilized multi-slice multi-echo (MSME) MR sequences. During imaging acquisitions, the animals were anesthetized with a continuous supply of 2% isoflurane in oxygen and were continuously monitored for respiration and temperature. After imaging experiments, we manually segmented the tumors on each image slice for quantitative image analyses. We computed three-dimensional T2 maps for the tumor regions from the MSME images. We plotted the histograms of the T2 maps for each tumor pre- and post-PDT and 24 hr after PDT. After the imaging and PDT experiments, we dissected the tumor tissues and used the histologic slides to validate the MR images. In this study, six mice with human prostate cancer tumors were imaged and treated at the Case Center for Imaging Research. The T2 values of treated tumors increased by 24 ± 14% 24 hr after the therapy. The control tumors did not demonstrate significant changes of the T2 values. Inflammation and necrosis were observed within the treated tumors 24 hour after the treatment. Preliminary results show that Pc 4-PDT is effective for the treatment of human prostate cancer in mice. The small animal MR imaging provides a useful tool to evaluate early tumor response to photodynamic therapy in mice.

Multiscale Fuzzy C-Means Image Classification for Multiple Weighted MR Images for the Assessment of Photodynamic Therapy in Mice.

We are investigating in vivo small animal imaging and analysis methods for the assessment of photodynamic therapy (PDT), an emerging therapeutic modality for cancer treatment. Multiple weighted MR images were acquired from tumor-bearing mice pre- and post-PDT and 24-hour after PDT. We developed an automatic image classification method to differentiate live, necrotic and intermediate tissues within the treated tumor on the MR images. We used a multiscale diffusion filter to process the MR images before classification. A multiscale fuzzy C-means (FCM) classification method was applied along the scales. The object function of the standard FCM was modified to allow multiscale classification processing where the result from a coarse scale is used to supervise the classification in the next scale. The multiscale fuzzy C-means (MFCM) method takes noise levels and partial volume effects into the classification processing. The method was validated by simulated MR images with various noise levels. For simulated data, the classification method achieved 96.0 ± 1.1% overlap ratio. For real mouse MR images, the classification results of the treated tumors were validated by histologic images. The overlap ratios were 85.6 ± 5.1%, 82.4 ± 7.8% and 80.5 ± 10.2% for the live, necrotic, and intermediate tissues, respectively. The MR imaging and the MFCM classification methods may provide a useful tool for the assessment of the tumor response to photodynamic therapy in vivo.

Deformable and rigid registration of MRI and microPET images for photodynamic therapy of cancer in mice.

We are investigating imaging techniques to study the tumor response to photodynamic therapy (PDT). Positron emission tomography (PET) can provide physiological and functional information. High-resolution magnetic resonance imaging (MRI) can provide anatomical and morphological changes. Image registration can combine MRI and PET images for improved tumor monitoring. In this study, we acquired high-resolution MRI and microPET 18F-fluorodeoxyglucose (FDG) images from C3H mice with RIF-1 tumors that were treated with Pc 4-based PDT. We developed two registration methods for this application. For registration of the whole mouse body, we used an automatic three-dimensional, normalized mutual information algorithm. For tumor registration, we developed a finite element model (FEM)-based deformable registration scheme. To assess the quality of whole body registration, we performed slice-by-slice review of both image volumes; manually segmented feature organs, such as the left and right kidneys and the bladder, in each slice; and computed the distance between corresponding centroids. Over 40 volume registration experiments were performed with MRI and microPET images. The distance between corresponding centroids of organs was 1.5 +/- 0.4 mm which is about 2 pixels of microPET images. The mean volume overlap ratios for tumors were 94.7% and 86.3% for the deformable and rigid registration methods, respectively. Registration of high-resolution MRI and microPET images combines anatomical and functional information of the tumors and provides a useful tool for evaluating photodynamic therapy.

A simplified method for preparation of 99mTc-annexin V and its biologic evaluation for in vivo imaging of apoptosis after photodynamic therapy.

UNLABELLED: Apoptosis is the likely mechanism behind the effects of chemotherapeutic and radiation treatments, rejection of organ transplants, and cell death due to hypoxic-ischemic injury. A simplified method capable of imaging apoptosis in living animals could have many applications leading to understanding of the involvement of apoptosis in biologic and therapeutic processes. To accomplish this goal we developed a method for the preparation of (99m)Tc-annexin V and evaluated its usefulness to detect apoptosis that occurs during tumor shrinkage after photodynamic therapy (PDT). PDT is a cancer treatment modality that leads to rapid induction of apoptosis both in vitro and in in vivo animal models. METHODS: A novel synthesis of (99m)Tc-annexin V was performed in a simple 1-pot procedure. Radiation-induced fibrosarcoma (RIF-1) tumors grown in C(3)H mice were treated with PDT, followed by injection of (99m)Tc-annexin V and measurement of its tumor uptake at 2, 4, and 7 h after PDT by autoradiography. RESULTS: The radiochemical purity of (99m)Tc-annexin V was >95%. At all time points, (99m)Tc-annexin V was clearly imaged in the PDT-treated tumors, whereas the untreated tumors showed no uptake of the radiolabeled compound. Histopathology and immunohistochemistry of PDT-treated tumors confirmed the evidence of apoptosis compared with untreated tumors. CONCLUSION: These data demonstrate the detection of apoptosis using (99m)Tc-annexin V in tumor tissue in living animals after PDT treatment. This novel technique could be used as a noninvasive means to detect and serially image tissues undergoing apoptosis after cancer treatment protocols in humans. Other potential applications of this technique could be the diagnosis of several human disorders, such as myocardial ischemia or infarct, rejection of organ transplantation, and neonatal cerebral ischemia.