A pre-implementation examination of barriers and facilitators of an electronic prospective surveillance model for cancer rehabilitation: a qualitative study.

BACKGROUND: An electronic Prospective Surveillance Model (ePSM) uses patient-reported outcomes to monitor symptoms along the cancer pathway for timely identification and treatment. Randomized controlled trials show that ePSMs can effectively manage treatment-related adverse effects. However, an understanding of optimal approaches for implementing these systems into routine cancer care is limited. This study aimed to identify barriers and facilitators prior to the implementation of an ePSM to inform the selection of implementation strategies. METHODS: A qualitative study using virtual focus groups and individual interviews was conducted with cancer survivors, oncology healthcare providers, and clinic leadership across four cancer centres in Canada. The Consolidated Framework for Implementation Research (CFIR) guided the interviews and analysis of barriers and facilitators based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process). RESULTS: We conducted 13 focus groups and nine individual interviews with 13 patient participants and 56 clinic staff. Of the 39 CFIR constructs, 18 were identified as relevant determinants to the implementation. The adaptability, relative advantage, and complexity of an ePSM emerged as key intervention-level factors that could influence implementation. Knowledge of the system was important at the individual level. Within the inner setting, major determinants were the potential fit of an ePSM with clinical workflows (compatibility) and the resources that could be dedicated to the implementation effort (readiness for implementation). In the outer setting, meeting the needs of patients and the availability of rehabilitation supports were key determinants. Engaging various stakeholders was critical at the process level. CONCLUSIONS: Improving the implementation of ePSMs in routine cancer care has the potential to facilitate early identification and management of treatment-related adverse effects, thereby improving quality of life. This study provides insight into important factors that may influence the implementation of an ePSM, which can be used to select appropriate implementation strategies to address these factors.

Real-world outcomes with bortezomib-containing regimens and lenalidomide plus dexamethasone for the treatment of transplant-ineligible multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group database.

Bortezomib-containing regimens (BCRs) represented standard, first-line therapy for transplant-ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low-dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low-dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression-free survival (PFS) was 21·0, 21·1, 13·2 and 28·5 months (P = 0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7 months (P < 0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib-steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician's choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real-world outcomes in TIMM similar to those reported in clinical trials.

Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial.

The MCRN-003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)-free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m2 ), dexamethasone 40 mg and cyclophosphamide 300 mg/m2 was delivered over 28-day cycles. The primary endpoint was overall response after four cycles. Secondary endpoints included toxicity, response depth, PFS and OS. Exploratory endpoints included the impact of cytogenetics, prior therapy exposure and serum free light chain (sFLC) escape; 76 patients were accrued. The ORR was 85% (68% ≥very good partial response [VGPR] and 29% ≥complete response [CR]). The median OS and PFS were 27 and 17 months respectively. High-risk cytogenetics conferred a worse ORR (75% vs. 97%, p = .013) and median OS (18 months vs. NR, p = .002) with a trend toward a worse median PFS (14 vs. 22 months, p = .06). Prior proteasome inhibitor (PI) or lenalidomide did not influence OS or PFS. The sFLC was noted in 15% of patients with a median PFS of 17 months when included as a progression event. The most common ≥ grade 3 non-hematologic adverse events were infectious (40%), vascular (17%) and cardiac (15%). The wKCD is a safe and effective regimen in relapse, especially for patients ineligible for lenalidomide-based therapies.

Antimyeloma Potential of Caffeic Acid Phenethyl Ester and Its Analogues through Sp1 Mediated Downregulation of IKZF1-IRF4-MYC Axis.

Caffeic acid phenethyl ester (CAPE, 2), a natural compound from propolis, is a well-documented antitumor agent with nuclear factor kappa B (NF-κB) inhibitory activity. Key transcription factors regulated by NF-κB, namely, interferon regulatory factor-4 (IRF4) and octameric binding protein-2 (OCT2), are implicated in the tumorigenesis of multiple myeloma (MM), an incurable bone marrow cancer. Adverse effects and resistance to current chemotherapeutics pose a great challenge for MM treatment. Hence, the structure-activity relationships of CAPE (2) and 21 of its analogues were evaluated for their antimyeloma potential. Preclinical evaluation revealed that CAPE (2) and the 3-phenylpropyl (4), 2,5-dihydroxycinnamic acid 3-phenylpropyl ester (17), and 3,4-dihydroxycinnamic ether (22) analogues inhibited human myeloma cell growth. Analogue 4 surpassed CAPE (2) and lenalidomide in showing strong apoptotic effects with a remarkable decrease in IRF4 levels. The analogue 17 exhibited the most potent anti-MM activity. The downregulation of specificity protein 1 (Sp1) and the IKZF1-IRF4-MYC axis by CAPE (2) analogues 4 and 17 revealed their novel mechanism of action. The analogues showed no adverse cytotoxic effects on normal human cells and exhibited appropriate in silico pharmacokinetic properties and drug-likeness. These findings suggest the promising application of CAPE (2) analogues to target Ikaros (IKZF1)/IRF4 addiction, the so-called Achilles heel of myeloma, for better treatment outcomes.

Making It Happen: Middle Managers' Roles in Innovation Implementation in Health Care.

BACKGROUND: Middle managers are given scant attention in the implementation literature in health care, where the focus is on senior leaders and frontline clinicians. AIMS: To empirically examine the role of middle managers relevant to innovation implementation and how middle managers experience the implementation process. METHODS: A qualitative study was conducted using the methods of grounded theory. Data were collected through semistructured interviews with middle managers (N = 15) in Nova Scotia and New Brunswick, Canada. Participants were purposively sampled, based on their involvement in implementation initiatives and to obtain variation in manager characteristics. Data were collected and analyzed concurrently, using an inductive constant comparative approach. Data collection and analysis continued until theoretical saturation was reached. RESULTS: Middle managers see themselves as being responsible for making implementation happen in their programs and services. As a result, they carry out five roles related to implementation: planner, coordinator, facilitator, motivator, and evaluator. However, the data also revealed two determinants of middle managers' role in implementation, which they must negotiate to fulfill their specific implementation roles and activities: (1) They perform many other roles and responsibilities within their organizations, both clinical and managerial in nature, and (2) they have limited decision-making power with respect to implementation and must work within the parameters set by upper levels of the organization. LINKING EVIDENCE TO ACTION: Middle managers play an important role in translating adoption decisions into on-the-ground implementation. Optimizing their capacity to fulfill this role may be key to improving innovation implementation in healthcare organizations.

Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma.

BACKGROUND: Patients with T-cell lymphomas face a poorer prognosis compared with patients with B-cell lymphomas. New therapeutic approaches need to be developed to improve outcomes for these patients. METHODS: Forty patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy were prescribed oral lenalidomide at a dose of 25 mg daily on days 1 to 21 of each 28-day cycle, with standardized dose reductions for toxicity. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete and partial response rates, progression-free survival (PFS), overall survival (OS), and safety. The authors also determined duration of response (DoR). RESULTS: A total of 40 patients were enrolled in the current study; 1 patient was subsequently deemed ineligible. The ORR was 10 of 39 patients (26%); 3 patients (8%) achieved complete responses and 7 patients achieved partial responses. Three patients had stable disease for ≥5 cycles. The median OS was 12 months (range <1 month to ≥69 months), the median PFS was 4 months (range, <1 month to ≥50 months), and the median DoR was 13 months (range 2 months to ≥37 months), including 5 responses that lasted >1 year. Toxicity was in keeping with the known safety profile of lenalidomide. Among the patients who had recurrent/refractory peripheral T-cell lymphoma (29 patients), the ORR was 24%, the median OS was 12 months, the median PFS was 4 months, and the median DoR was 5 months (range, 2 months to ≥37 months). CONCLUSIONS: In the current study, the use of oral lenalidomide monotherapy demonstrated clinically relevant efficacy among patients with systemic T-cell lymphomas. It appears to have excellent potential as an agent in combination therapy for patients with T-cell lymphoma.

Effects of supervised exercise on progression-free survival in lymphoma patients: an exploratory follow-up of the HELP Trial.

PURPOSE: Few randomized controlled trials in exercise oncology have examined survival outcomes. Here, we report an exploratory follow-up of progression-free survival (PFS) from the Healthy Exercise for Lymphoma Patients (HELP) Trial. METHODS: The HELP Trial randomized 122 lymphoma patients between 2005 and 2008 to either control (n = 62) or 12 weeks of supervised aerobic exercise (n = 60). PFS events were abstracted from medical records in 2013. In addition to the randomized comparison, we explored the effects of exercise adherence (<80 % vs. ≥80 %) and control group crossover (no vs. yes). RESULTS: After a median follow-up of 61 months (interquartile range 36-67), the adjusted 5-year PFS was 64.8 % for the exercise group compared with 65.0 % for the control group (Hazard ratio [HR] 1.01, 95 % CI 0.51-2.01, p = 0.98). In the secondary analysis, the adjusted 5-year PFS was 59.0 % in the control group without crossover compared with 69.2 % for the control group with crossover (HR 0.68, 95 % CI 0.22-2.06, p = 0.49), 67.7 % for the exercise group with <80 % adherence (HR 0.72, 95 % CI 0.28-1.85, p = 0.50), and 68.4 % for the exercise group with ≥80 % adherence (HR 0.70, 95 % CI 0.32-1.56, p = 0.39). In a post hoc analysis combining the three groups that received supervised exercise, the adjusted 5-year PFS for the supervised exercise groups was 68.5 % compared with 59.0 % for the group that received no supervised exercise (HR 0.70, 95 % CI 0.35-1.39, p = 0.31). CONCLUSIONS: This exploratory follow-up of the HELP Trial suggests that supervised aerobic exercise may be associated with improved PFS in lymphoma patients. Larger trials designed to answer this question are needed.

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial.

We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m2. The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival,progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio = 0.77; P = .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomide-prednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit.

Patient satisfaction with participation in a randomized exercise trial: effects of randomization and a usual care posttrial exercise program.

BACKGROUND: Participation in an exercise trial is a major commitment for cancer survivors, but few exercise trials have evaluated patient satisfaction with trial participation. PURPOSE: To examine patient satisfaction with participation in the Healthy Exercise for Lymphoma Patients (HELP) Trial and to explore possible determinants. METHODS: The HELP Trial randomized 122 lymphoma patients to 12 weeks of supervised aerobic exercise training (AET; n = 60) or to usual care (UC; n = 62), with the option of participating in a 4-week posttrial exercise program. At the 6-month follow-up assessment, participants evaluated their overall trial satisfaction. RESULTS: Personal satisfaction with trial participation was strongly influenced by group assignment with participants randomized to AET reporting participation to be more rewarding (p < 0.001) and personally useful (p < 0.001) than participants randomized to UC. UC participants who completed the optional 4-week posttrial exercise program reported participation to be more rewarding (p = 0.008) and personally useful (p < 0.001) than UC participants who declined the program. LIMITATIONS: The study is limited by the lack of a validated measure of participant satisfaction, and the fact that the offer of participation in the posttrial exercise program to the UC group was not randomized. CONCLUSIONS: Lymphoma patients randomized to UC viewed it as less rewarding and personally useful despite being offered a 4-week posttrial exercise program. UC participants who completed the 4-week program reported personal satisfaction levels similar to the AET group; however, the causal direction of this association is unknown. Researchers should continue to evaluate participant satisfaction in exercise trials.

TAZ upregulates MIR-224 to inhibit oxidative stress response in multiple myeloma.

BACKGROUND: Oxidative stress within the bone marrow niche of multiple myeloma contributes to disease progression and drug resistance. Recent studies have associated the Hippo pathway with miRNA biogenesis and oxidative stress in solid tumors. Oxidative stress and miRNA pathway inter-relates in several cancers. Our group recently showed that TAZ functions as a tumor suppressor in MM. However, the role of TAZ in oxidative stress in MM is unknown. AIMS: We sought to examine the role of TAZ in myeloma cells' response to BM oxidative stress. We postulated that TAZ might be associated with an oxidative stress phenotype and distinct miRNA signature in MM. METHODS AND RESULTS: Using human myeloma cell lines and clinical samples, we demonstrate that TAZ promotes myeloma cells' sensitivity to oxidative stress and anticancer-induced cytotoxicity by inducing miR-224 to repress the NRF2 antioxidant program in MM. We show that low expression of TAZ protein confers an oxidative stress-resistant phenotype in MM. Furthermore, we provide evidence that overexpression of miR-224 in myeloma cells expressing low amounts of TAZ protein inhibits cell growth and enhances sensitivity to anti-myeloma therapeutics. CONCLUSION: Our findings uncover a potential role for TAZ in oxidative stress response in MM via the miR-224-NRF2 molecular pathway. This provides the scientific ground to explore miR-224 as a potential molecular target to modify TAZ expression and enhance myeloma sensitivity to treatment.

MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target.

We have previously reported that transcriptional activator with PDZ-binding motif (TAZ) functions as a tumor suppressor in multiple myeloma (MM). MST1 is a serine-threonine kinase upstream of the Hippo-signaling pathway that functions as a tumor suppressor in many non-hematologic malignancies. However, its role in hematologic malignancies, including MM is still poorly understood. In this article, we provide evidence that MST1 expression is higher in MM and negatively correlates with TAZ expression in both cell lines and patient samples. High MST1 expression was associated with poor clinical outcomes. Genetic or pharmacologic inhibition of MST1 leads to increased TAZ expression and cell death. Importantly, MST1 inhibitors sensitize myeloma cells to frontline antimyeloma agents-lenalidomide and dexamethasone. Taken together, our data reveal a key role for MST1 in MM pathogenesis and provide evidence to explore the therapeutic potential of using MST inhibitors to upregulate TAZ expression in MM to promote response to anticancer agents.

Implementation of electronic prospective surveillance models in cancer care: a scoping review.

BACKGROUND: Electronic prospective surveillance models (ePSMs) for cancer rehabilitation include routine monitoring of the development of treatment toxicities and impairments via electronic patient-reported outcomes. Implementing ePSMs to address the knowledge-to-practice gap between the high incidence of impairments and low uptake of rehabilitation services is a top priority in cancer care. METHODS: We conducted a scoping review to understand the state of the evidence concerning the implementation of ePSMs in oncology. Seven electronic databases were searched from inception to February 2021. All articles were screened and extracted by two independent reviewers. Data regarding the implementation strategies, outcomes, and determinants were extracted. The Expert Recommendations for Implementing Change taxonomy and the implementation outcomes taxonomy guided the synthesis of the implementation strategies and outcomes, respectively. The Consolidated Framework for Implementation Research guided the synthesis of determinants based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process). RESULTS: Of the 5122 records identified, 46 interventions met inclusion criteria. The common implementation strategies employed were "conduct educational meetings," "distribute educational materials," "change record systems," and "intervene with patients to enhance uptake and adherence." Feasibility and acceptability were the prominent outcomes used to assess implementation. The complexity, relative advantage, design quality, and packaging were major implementation determinants at the intervention level. Knowledge was key at the individual level. At the inner setting level, major determinants were the implementation climate and readiness for implementation. At the outer setting level, meeting the needs of patients was the primary determinant. Engaging various stakeholders was key at the process level. CONCLUSIONS: This review provides a comprehensive summary of what is known concerning the implementation of ePSMs. The results can inform future implementation and evaluation of ePSMs, including planning for key determinants, selecting implementation strategies, and considering outcomes alongside local contextual factors to guide the implementation process.

In non-transplant patients with multiple myeloma, the pre-treatment level of clonotypic cells predicts event-free survival.

BACKGROUND: In multiple myeloma (MM), the immunoglobulin heavy chain VDJ gene rearrangement is a unique clonotypic signature that identifies all members of the myeloma clone independent of morphology or phenotype. Each clonotypic MM cell has only one genomic copy of the rearranged IgH VDJ. METHODS: Pre-treatment bone marrow aspirates from myeloma patients at diagnosis or in relapse were evaluated for the number of clonotypic cells using real time quantitative PCR (RPCR). RPCR measured the level of clonal cells, termed VDJ%, in 139 diagnosis and relapse BM aspirates from MM patients. RESULTS: Patients with a VDJ% below the median had a significantly longer event free survival (EFS) then those with a VDJ% higher than the median (p=0.0077, HR=0.57). Further, although the VDJ% from non-transplant patients predicted EFS (p=0.0093), VDJ% failed to predict outcome after autologous stem cell transplant (p=0.53). CONCLUSIONS: Our results suggest that for non-transplant patients, the tumor burden before treatment, perhaps reflecting cancer stem cell progeny/output, is an indirect measure that may indicate the number of MM cancer stem cells and hence event free survival.

Predictors of follow-up exercise behavior 6 months after a randomized trial of supervised exercise training in lymphoma patients.

OBJECTIVES: Supervised exercise is beneficial for lymphoma patients, but it needs to be maintained to optimize long-term benefits. Here, we report the predictors of follow-up exercise behavior 6 months after a randomized controlled trial in lymphoma patients. METHODS: Lymphoma patients were randomly assigned to 12 weeks of supervised aerobic exercise (n = 60) or usual care (n = 62). At baseline and post-intervention, data were collected on demographic, medical, health-related fitness, quality of life, and motivational variables. At 6-month follow-up, participants were mailed a questionnaire that assessed exercise behavior and were categorized as meeting or not meeting public health exercise guidelines. RESULTS: At 6-month follow-up, 110 participants (90.2%) responded, of which 61 (55.5%) were meeting public health exercise guidelines. In univariate analyses, 16 variables predicted 6-month follow-up exercise behavior. In a stepwise regression analysis, five variables entered the model and explained 38% (p < 0.001) of the variance including the following: accepting a post-intervention exercise prescription (ß = 0.33; p < 0.001), achieving a higher peak power output at post-intervention (ß = 0.28; p = 0.001), experiencing a larger positive change in perceived behavioral control (ß = 0.18; p = 0.028), having Hodgkin lymphoma (ß = 0.19; p = 0.025), and having a stronger post-intervention intention (ß = 0.18; p = 0.034). CONCLUSION: Exercise behavior in lymphoma patients 6 months after a randomized trial was predicted by a wide range of demographic, medical, health-related fitness, quality of life, and motivational variables. These findings may help facilitate the uptake of self-directed exercise after short-term supervised exercise in lymphoma patients.

Dietary patterns of patients with advanced lung or colorectal cancer.

The purpose of this study was to identify dietary patterns among patients with advanced cancer. Differences between cancer groups are described, and food groups contributing higher proportions to overall caloric intake are identified. Patients with advanced cancer (n=51) were recruited from a regional cancer centre and completed a three-day dietary record. Food items were categorized according to macronutrient content. After adjustment for body weight, substantial variation in energy intake was observed (range: 13.7 to 55.4 kcal/kg/day). For 49% of patients, protein intake was below recommendations. Overall, patients consumed the largest proportion of their calories from meat (16%), other foods (11%), dessert (9%), fruit (9%), white bread (7%), and milk (7%). Only 5% of patients consumed meal replacement supplements. The results of this descriptive study provide important insights into the dietary habits of patients with advanced cancer. These insights could be translated into the development of effective recommendations for maintaining or improving health and quality of life.

Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer.

BACKGROUND: Palliative chemotherapy is aimed at increasing survival and palliating symptoms. However, the response rate to first-line chemotherapy in patients with nonsmall cell lung cancer (NSCLC) is less than 30%. Experimental studies have shown that supplementation with fish oil (FO) can increase chemotherapy efficacy without negatively affecting nontarget tissue. This study evaluated whether the combination of FO and chemotherapy (carboplatin with vinorelbine or gemcitabine) provided a benefit over standard of care (SOC) on response rate and clinical benefit from chemotherapy in patients with advanced NSCLC. METHODS: Forty-six patients completed the study, n = 31 in the SOC group and n = 15 in the FO group (2.5 g EPA + DHA/day). Response to chemotherapy was determined by clinical examination and imaging. Response rate was defined as the sum of complete response plus partial response, and clinical benefit was defined as the sum of complete response, partial response, and stable disease divided by the number of patients. Toxicities were graded by a nurse before each chemotherapy cycle. Survival was calculated 1 year after study enrollment. RESULTS: Patients in the FO group had an increased response rate and greater clinical benefit compared with the SOC group (60.0% vs 25.8%, P = .008; 80.0% vs 41.9%, P = .02, respectively). The incidence of dose-limiting toxicity did not differ between groups (P = .46). One-year survival tended to be greater in the FO group (60.0% vs 38.7%; P = .15). CONCLUSIONS: Compared with SOC, supplementation with FO results in increased chemotherapy efficacy without affecting the toxicity profile and may contribute to increased survival.

Nanoparticle surface-enhanced Raman spectroscopy as a noninvasive, label-free tool to monitor hematological malignancy.

Aim: Monitoring minimal residual disease remains a challenge to the effective medical management of hematological malignancies; yet surface-enhanced Raman spectroscopy (SERS) has emerged as a potential clinical tool to do so. Materials & methods: We developed a cell-free, label-free SERS approach using gold nanoparticles (nanoSERS) to classify hematological malignancies referenced against two control cohorts: healthy and noncancer cardiovascular disease. A predictive model was built using machine-learning algorithms to incorporate disease burden scores for patients under standard treatment upon. Results: Linear- and quadratic-discriminant analysis distinguished three cohorts with 69.8 and 71.4% accuracies, respectively. A predictive nanoSERS model correlated (MSE = 1.6) with established clinical parameters. Conclusion: This study offers a proof-of-concept for the noninvasive monitoring of disease progression, highlighting the potential to incorporate nanoSERS into translational medicine.

Cancer patient quality of life is achieved by reassurance from informed doctors using the best clinical tools. Confirming the earliest detection or absence of disease ensures treatment is timely and recovery optimal. Here we show the potential for a new tool to be developed to reassure patients and inform doctors. We examined the 'chemical fingerprints' (Raman spectroscopic profiling) of patient's blood, enhanced by gold nanoparticles with a double-referenced machine learning algorithm. Teaching a machine to learn as it works ensures it is improving how it finds clinically important features in the chemical fingerprint. This helps patients live more confidently with cancer or in cancer recovery. Eventually, once fully trained and translated into a real-world hospital application, this could improve patient outcomes and quality of life.

A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma.

Although the in vitro expansion of the multiple myeloma (MM) clone has been unsuccessful, in a novel three-dimensional (3-D) culture model of reconstructed bone marrow (BM, n = 48) and mobilized blood autografts (n = 14) presented here, the entire MM clone proliferates and undergoes up to 17-fold expansion of malignant cells harboring the clonotypic IgH VDJ and characteristic chromosomal rearrangements. In this system, MM clone expands in a reconstructed microenvironment that is ideally suited for testing specificity of anti-MM therapeutics. In the 3-D model, melphalan and bortezomib had distinct targets, with melphalan targeting the hematopoietic, but not stromal com-partment. Bortezomib targeted only CD138(+)CD56(+) MM plasma cells. The localization of nonproliferating cells to the reconstructed endosteum, in contact with N-cadherin-positive stroma, suggested the presence of MM-cancer stem cells. These drug-resistant CD20(+) cells were enriched more than 10-fold by melphalan treatment, exhibited self-renewal, and generated clonotypic B and plasma cell progeny in colony forming unit assays. This is the first molecularly verified demonstration of proliferation in vitro by ex vivo MM cells. The 3-D culture provides a novel biologically relevant preclinical model for evaluating therapeutic vulnerabilities of all compartments of the MM clone, including presumptive drug-resistant MM stem cells.