Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.

Quality-adjusted time without symptoms or toxicity analysis of nivolumab plus chemotherapy versus chemotherapy alone for the management of previously untreated patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

BACKGROUND: The phase 3 CheckMate 649 established superior overall survival of nivolumab in combination with chemotherapy (NIVO + chemo) compared with chemotherapy (chemo) alone as a first-line treatment for patients with Her2-negative advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC). This post hoc trial analysis aimed to evaluate the benefit of NIVO + chemo using quality-adjusted time without symptoms or toxicity (Q-TWiST) to further account for quality of life (QoL) in different health states depending on disease progression and treatment toxicity. METHODS: Using data from CheckMate 649, we evaluated the quality-adjusted survival gain associated with NIVO + chemo compared with chemo alone among all randomized patients and repeated similar analyses among those with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 5. Relative Q-TWiST gains of ≥ 10% were predefined as clinically important. RESULTS: In all randomized patients, those receiving NIVO + chemo had a mean Q-TWiST gain of 1.8 (95% CI 0.9, 2.7) months compared with those receiving chemo alone. The relative Q-TWiST gain was estimated to be 12.8%. Patients with PD-L1 CPS ≥ 5 had greater quality-adjusted survival gain from NIVO + chemo with an estimated Q-TWiST gain of 2.8 (95% CI 1.5, 4.1) months, representing a relative gain of 20.6%. Subgroup analyses and sensitivity analyses with various QoL utility values yielded consistent findings in favor of NIVO + chemo compared with chemo alone. Q-TWiST gain from NIVO + chemo increased with longer duration of follow-up. CONCLUSIONS: NIVO + chemo was associated with a statistically significant and clinically important gain in quality-adjusted survival compared with chemo alone among previously untreated patients with advanced GC/GEJC/EAC.

The burden of ovarian cancer in the USA from 2007 to 2018: evidence from the Medical Expenditure Panel Survey.

Aim: To evaluate the economic and humanistic burden of ovarian cancer in the USA. Methods: Medical Expenditure Panel Survey data (2007-2018) were used to estimate all-cause healthcare resource use and costs for economic burden and examine the activities of daily living and quality-of-life (QoL) measures for humanistic burden between ovarian cancer patients and a non-cancer population. Results: Compared with controls, patients with ovarian cancer had more comorbidities and worse QoL. Their predicted number of annual hospitalizations and office-based visits was significantly higher, as were their estimated annual all-cause total healthcare costs. Total costs were driven by hospitalization costs. Conclusion: The study identified the burden of ovarian cancer and demonstrated that patients with ovarian cancer have greater healthcare resource use, higher costs and worse QoL than the non-cancer population. Future research is needed to develop strategies for managing ovarian cancers and inform decision-making to reduce disease burden.

What is this article about? The article discusses the impact that ovarian cancer has, both in terms of economics and quality of life. We used data from 2007 to 2018 to identify women with ovarian cancer as well as women without cancer for the sake of comparison. What were the results? We found that individuals with ovarian cancer face considerable burdens, and their treatment costs have a notable impact on healthcare systems. Compared with women without cancer, women with ovarian cancer are older and have a greater number of additional illnesses, and their quality of life is lower. Their use of healthcare resources is greater and hence the costs associated with their treatment are higher. What do the results of the study mean? This study adds to the existing data about the burden imposed by ovarian cancer, on individuals as well as on healthcare systems. Interventions are needed to reduce the impacts of the disease.

Financial toxicity and its impact on health outcomes and caregiver burden among adult cancer survivors in the USA.

Aim: To examine the association between cancer-related financial toxicity on cancer survivors' physical and mental health outcomes and caregiver burden. Materials & methods: 2016-2017 Medical Expenditure Panel Survey data were used to identify adult cancer survivors with cancer-related financial toxicity. Multivariable regression analyses were employed to examine the association between cancer-related financial toxicity and cancer survivors' self-reported physical and mental health outcomes and caregiver burden. Results: A total of 53.7% of adult cancer survivors reported experiencing financial toxicity. Those who experienced financial toxicity reported 14% greater pain, and poorer physical and mental health outcomes as compared to those who did not experience financial toxicity, ranging from 38% greater odds for activity limitations to 427% greater odds for mental task limitation. Moreover, cancer survivors with financial toxicity reported 206% greater odds for caregiver burden. Conclusions: Intervention programs for reducing financial toxicity among adult cancer survivors and their caregivers should be developed.

The cost of cancer care has increased substantially over the past decade imposing significant financial burden on cancer survivors, with a growing number of cancer survivors experiencing financial toxicity. Using the Cancer Self-Administered Questionnaire of the Medical Expenditure Panel Survey, this study estimated the impact of cancer-related financial toxicity on cancer survivors' self-reported health outcomes and caregiver burden. The results highlight the impact of financial toxicity on cancer survivors' physical health and mental health outcomes and caregiver burden in a nationally representative sample of noninstitutionalized adults in the USA. The study findings document the critical need to develop interventions and implement structural policy changes aimed at identifying and reducing financial toxicity among adult cancer survivors and their caregivers.

Treatment patterns and economic burden among cervical and endometrial cancer patients newly initiating systemic therapy.

Aim: To evaluate treatment patterns, healthcare resource use (HCRU) and all-cause healthcare costs among patients with cervical or endometrial cancer newly initiating systemic therapy. Methods: We identified patients with cervical or endometrial cancer newly initiating systemic therapy - a claims-based proxy for advanced disease - between 2014 and 2019, described them by line of therapy (LOT), and summarized the per patient per month (PPPM) HCRU and healthcare costs per LOT. Results: Among 1229 patients with cervical cancer and 2659 patients with endometrial cancer, LOT1 therapies included systemic only (cervical, 50.1%; endometrial, 83.2%) and systemic with radiation therapy (cervical, 49.9%; endometrial, 16.8%). Mean PPPM total costs were: LOT1 (cervical, US$15,892; endometrial, US$11,363), LOT2 (US$20,193; US$14,019) and LOT3+ (US$16,576; US$14,645). Conclusions: Overall, patients received guideline-concordant care and experienced significant economic burden, which increased with LOT.

Treatment patterns and economic burden among newly diagnosed cervical and endometrial cancer patients.

Aim: This study evaluated treatment patterns, healthcare resource use and healthcare costs among newly diagnosed US patients with cervical or endometrial cancer. Materials & methods: The authors identified patients diagnosed between 2015 and 2018, described them by line of therapy (LOT), then summarized all-cause per patient per month healthcare resource use and healthcare costs per LOT. Results: Among 1004 patients with cervical cancer and 2006 patients with endometrial cancer, 65.2 and 71.4%, respectively, received at least LOT1. Common treatment modalities in LOT1 were surgery (cervical, 58.0%; endometrial, 92.6%), radiation therapy (cervical, 49.8%; 24.7%) and systemic therapy (cervical, 53.3%; endometrial, 26.1%). Mean per patient per month costs per LOT were pre-treatment (cervical, US$17,210; endometrial, US$14,601), LOT1 (cervical, US$10,929; endometrial, US$6859), LOT2 (cervical, US$15,183; endometrial, US$10,649) and LOT3+ (cervical, US$19,681; endometrial, US$9206). Conclusion: Overall, newly diagnosed patients with cervical or endometrial cancer received guideline-recommended treatment. Outpatient visits mainly drove healthcare costs across LOTs.

Placental morphology in association with autism-related traits in the EARLI study.

BACKGROUND: In prior work we observed differences in morphology features in placentas from an autism-enriched cohort as compared to those from a general population sample. Here we sought to examine whether these differences associate with ASD-related outcomes in the child. METHODS: Participants (n = 101) were drawn from the Early Autism Risk Longitudinal Investigation (EARLI), a cohort following younger siblings of children with autism spectrum disorder (ASD). ASD-related outcomes, including the Social Responsiveness Scale (SRS), Mullen Scales of Early Learning (MSEL) Early Learning Composite, and ASD diagnosis, were assessed at age 3. Crude and adjusted linear regression was used to examine associations between placental morphological features (parametrized continuously and in quartiles) and SRS and MSEL scores; comparisons by ASD case status were explored as secondary analyses due to the small number of cases (n = 20). RESULTS: In adjusted analyses, we observed a modest positive association between umbilical cord eccentricity, defined as the ratio of the maximum:minimum radius from the cord insertion point, and SRS scores (Beta = 1.68, 95%CI = 0.45, 2.9). Positive associations were also suggested between placental maximum thickness and cord centrality and SRS scores, though these were estimated with little precision. Associations between other placental morphological features and outcomes were not observed. CONCLUSIONS: Our analyses suggested a potential association between umbilical cord features and ASD-related traits, of interest as non-central cord insertion may reflect reduced placenta efficiency. Future studies with larger sample sizes are needed to further examine these and other placental features in association with ASD-related outcomes.

"Virtual Biopsies" of Normal Skin and Thermal and Chemical Burn Wounds.

The search for noninvasive methods to image and measure the mechanical properties of skin has been a frequent subject of research for many years. Although suction testing, elastography, and other testing can be noninvasive, these tests fail to yield comparable results to destructive tests such as uniaxial tensile testing. Accordingly, researchers have developed a technique to combine optical coherence tomography with vibrational analysis (vibrational optical coherence tomography) to image and analyze the biomechanical properties of tissues noninvasively and nondestructively. The result of this analysis is a "virtual biopsy" of skin, along with a physical analysis of the major components of the epidermis and dermis.In this study, the authors compare virtual biopsies of thermal and chemical burns to that of normal skin. They conclude that the enhanced optical coherence tomography images and measurements of the resonant frequency after thermal or chemical burns exhibit large differences when compared with the morphology and moduli of normal skin. Using vibrational optical coherence tomography, it is possible to follow changes in the morphology and physical properties of the epidermis and dermis associated with skin diseases and therapeutic treatments in situ.

Quality-adjusted survival of nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma: a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis.

PURPOSE: To compare the quality-adjusted survival of nivolumab plus ipilimumab combination and nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma based on a minimum 36-month follow-up from the CheckMate 067 trial. METHODS: Overall survival was partitioned into time without symptoms of progression or toxicity (TWiST), time with treatment-related grade ≥ 3 adverse events after randomization but before progression (TOX), and time from progression until end of follow-up or death (REL). Mean quality-adjusted TWiST (Q-TWiST) was calculated by multiplying the mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Sensitivity analyses included varying utilities of TOX and REL; Q-TWiST gains at different follow-up times were calculated using EQ-5D-3L utilities from the trial. Relative Q-TWiST gain of ≥ 10% was considered clinically important. RESULTS: Compared with ipilimumab-treated patients, those who received nivolumab + ipilimumab combination had significantly longer TWiST and TOX but shorter REL; nivolumab-treated patients had significantly longer TWiST, shorter REL, and shorter but statistically nonsignificant TOX. Mean Q-TWiST was highest for nivolumab + ipilimumab (23.5 months; 95% CI 21.9-25.2), followed by nivolumab (21.8 months; 95% CI 20.2-23.4) and ipilimumab (15.3 months; 95% CI 13.9-16.6). Relative Q-TWiST gains were favorable and clinically important for nivolumab + ipilimumab combination (+ 36.81%) and nivolumab alone (+ 29.18%) versus ipilimumab alone. Relative gains increased with follow-up from 3 to 40 months for all comparisons. These gains remained consistent in magnitude and direction in the different sensitivity analyses. CONCLUSIONS: Nivolumab + ipilimumab combination and nivolumab alone resulted in a statistically significant and clinically important improvement in quality-adjusted survival compared with ipilimumab alone.

Comparative "virtual biopsies" of normal skin and skin lesions using vibrational optical coherence tomography.

BACKGROUND: Increased tissue stiffness (also termed modulus) has been shown to be a characteristic of potential tumor metastasis. Measured values of the stiffness of tumors and cancer cells are reported in the literature to increase compared to neighboring normal tissues. Yet the relationship between the mechanical properties of cells and the extracellular matrix has yet to be correlated with the histopathology of cancerous lesions. MATERIALS AND METHODS: We have developed a technique to do virtual biopsies of skin lesions by combining images made using optical coherence tomography with stiffness measurements made simultaneously using vibrational analysis. The technique is termed vibrational optical coherence tomography (VOCT). RESULTS: In this paper, we report that precancerous and cancerous lesions are characterized by changes in both the morphology and stiffness of the cellular components of the skin. The ratio of the peak heights that correspond to the epidermal (40-60Hz) and dermal (140-160 Hz) resonant frequencies appear to be different for benign and cancerous or precancerous lesions compared with normal skin and scar. CONCLUSIONS: Cell-to-cell and epidermal-to-dermal interactions may be very important in evaluating the potential of skin lesions to become malignant. These interactions can be evaluated using VOCT, a new technique for performing "virtual biopsies" of skin lesions.

Anchor balloon, buddy wire, and wire and sheath techniques to deploy percutaneous pulmonary valves in tetralogy of fallot patients.

Advances in surgical techniques in tetralogy of Fallot (TOF) patients have improved survival of these patients into adulthood. The procedure requires right ventricular outflow tract or trans-annular patch with resultant pulmonary stenosis and/or regurgitation. As such, adult patients seen with this condition may have increasing right ventricular hypertrophy and/or right ventricular dilation. Recently, the Sapien XT valve (Edwards Lifesciences, CA) was approved by the FDA for pulmonary implantation. In some cases, advancing the valve in right ventricular outflow tract is difficult. This is a case series of delivering Sapien XT valves in TOF patients with severe pulmonary regurgitation and/or stenosis, using the anchor balloon, buddy wire, and the novel, wire and sheath techniques. © 2017 Wiley Periodicals, Inc.

Utility of the HAS-BLED Score in Risk Stratifying Patients on Dual Antiplatelet Therapy Post 12 Months After Drug-Eluting Stent Placement.

INTRODUCTION: Current guidelines recommend continuation of dual anti-platelet therapy (DAPT) for 12 months after percutaneous coronary intervention (PCI). Recent studies have shown benefit in continuing DAPT beyond 12 months but at the risk of increase bleeding. To date, there has been little data on risk stratifying patients to determine who can continue DAPT beyond 12 months at minimal bleeding risk. METHODS: All patients who underwent drug-eluting stent (DES) placement from January 1, 2013 to September 30, 2014 were reviewed. Patients who had follow-up for at least 12 months, placement of 2nd generation everolimus-coated DES, and were on DAPT for at least 12 months were included. Patients with a history of atrial fibrillation, follow-up time less than 12 months, or were on concurrent oral anticoagulation therapy were excluded. RESULTS: Five hundred thirty-one patients were analyzed as described above. Two hundred two patients included in our study with 7 patients in the bleeding cohort and 195 patients in no-bleed cohort. The HAS-BLED score in patients who had a bleeding episode vs. those who did not was 3.29 vs. 2.24 (P value of 0.0009). Although not statistically significant, patients who had a bleeding episode were more likely to have renal dysfunction, alcohol use, be on prasugrel, and be on 325mg of aspirin. CONCLUSION: The study shows that the HAS-BLED score can be of utility in risk stratifying patients in determining who can continue DAPT beyond 12 months. Furthermore, a HAS-BLED score of less than 2 may help guide extended DAPT beyond 12 months at minimal bleeding risk. © 2016 Wiley Periodicals, Inc.

Autism risk classification using placental chorionic surface vascular network features.

BACKGROUND: Autism Spectrum Disorder (ASD) is one of the fastest-growing developmental disorders in the United States. It was hypothesized that variations in the placental chorionic surface vascular network (PCSVN) structure may reflect both the overall effects of genetic and environmentally regulated variations in branching morphogenesis within the conceptus and the fetus' vital organs. This paper provides sound evidences to support the study of ASD risks with PCSVN through a combination of feature-selection and classification algorithms. METHODS: Twenty eight arterial and 8 shape-based PCSVN attributes from a high-risk ASD cohort of 89 placentas and a population-based cohort of 201 placentas were examined for ranked relevance using a modified version of the random forest algorithm, called the Boruta method. Principal component analysis (PCA) was applied to isolate principal effects of arterial growth on the fetal surface of the placenta. Linear discriminant analysis (LDA) with a 10-fold cross validation was performed to establish error statistics. RESULTS: The Boruta method selected 15 arterial attributes as relevant, implying the difference in high and low ASD risk can be explained by the arterial features alone. The five principal features obtained through PCA, which accounted for about 88% of the data variability, indicated that PCSVNs associated with placentas of high-risk ASD pregnancies generally had fewer branch points, thicker and less tortuous arteries, better extension to the surface boundary, and smaller branch angles than their population-based counterparts. CONCLUSION: We developed a set of methods to explain major PCSVN differences between placentas associated with high risk ASD pregnancies and those selected from the general population. The research paradigm presented can be generalized to study connections between PCSVN features and other maternal and fetal outcomes such as gestational diabetes and hypertension.

Treatment Patterns and Clinical Outcomes Among Patients with Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations Previously Treated with Platinum-Based Chemotherapy and Immunotherapy.

BACKGROUND: For patients with metastatic non-small cell lung cancer, timely molecular testing is essential to determine the appropriate course of therapy. Initial treatment with platinum chemotherapy and/or an immune checkpoint inhibitor (ICI) is the standard of care for patients without actionable genomic alterations. OBJECTIVE: We aimed to assess treatment patterns and clinical outcomes among patients with metastatic non-small cell lung cancer, no actionable genomic alterations, and with prior ICI and platinum-based chemotherapy in a community oncology setting. METHODS: This retrospective observational study examined electronic health records from adult patients with an initial metastatic non-small cell lung cancer diagnosis without actionable genomic alterations from 2017 to 2019. Patients had received a subsequent line of therapy (LOT) [index] after discontinuing platinum-based chemotherapy plus an ICI in the previous one or two LOTs. Patient demographics and clinical characteristics were analyzed descriptively. Clinical outcomes were evaluated using Kaplan-Meier analyses. RESULTS: Among the study population (n = 961), the most common index LOT regimens were non-platinum-based chemotherapies (57.3%), platinum-based chemotherapies (12.9%), ICI-based chemotherapies (12.7%), platinum + ICI-based chemotherapies (9.4%), and other (7.7%). The most common post-index LOT regimens were non-platinum based (61.2%), ICI based (15.3%), platinum based (10.7%), platinum + ICI based (3.2%), and other (2.5%). Median time to treatment discontinuation, time to next treatment, and overall survival were numerically longest with index LOT ICI-based regimens (6.5, 9.9, and 18.9 months, respectively) and shortest with platinum-based regimens (2.8, 5.3, and 8.0 months, respectively) and non-platinum-based regimens (2.6, 5.0, and 7.8 months, respectively). CONCLUSIONS: Among patients with metastatic non-small cell lung cancer without actionable genomic alterations previously treated with platinum + ICIs, non-platinum chemotherapy agents were most commonly prescribed in the index LOT. Clinical outcomes including time to treatment discontinuation, time to next treatment, and overall survival were short, highlighting the unmet need for more effective later-line treatments.

Maternal affective symptoms and sleep quality have sex-specific associations with placental topography.

BACKGROUND: The impacts of prenatal maternal affective symptoms on the placental structure are not well-established. Employing Geographic Information System (GIS) spatial autocorrelation, Moran's I, can help characterize placental thickness uniformity/variability and evaluate the impacts of maternal distress on placental topography. METHODS: This study (N = 126) utilized cohort data on prenatal maternal affective symptoms and placental 2D and 3D morphology. Prenatal maternal depression, stress, anxiety and sleep quality were scored for each trimester using the Edinburgh Postnatal Depression Scale (EPDS), Stressful Life Event Scale (SLE), Penn State Worry Questionnaire (PSWQ), and Pittsburgh Sleep Quality Index (PSQI), respectively. Placental shape was divided into Voronoi cells and thickness variability among these cells was computed using Moran's I for 4-nearest neighbors and neighbors within a 10 cm radius. Sex-stratified Spearman correlations and linear regression were used to study associations between mean placental thickness, placental GIS variables, placental weight and the average score of each maternal variable. RESULTS: For mothers carrying boys, poor sleep was associated with higher mean thickness (r = 0.308,p = 0.035) and lower placental thickness uniformity (r = -0.36,p = 0.012). Lower placental weight (r = 0.395,p = 0.003), higher maternal depression (r = -0.318,p = 0.019) and worry/anxiety (r = -0.362,p = 0.007) were associated with lower placental thickness uniformity for mothers carrying girls. LIMITATIONS: The study is exploratory and not all GIS models were developed. Excluding high-risk pregnancies prevented investigating pregnancy complications related hypotheses. A larger sample size is needed for greater confidence for clinical application. CONCLUSIONS: Placental topography can be studied using GIS theory and has shown that prenatal maternal affective symptoms and sleep have sex-specific associations with placental thickness.

PFAS alters placental arterial vasculature in term human placentae: A prospective pregnancy cohort study.

INTRODUCTION: Perfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. OBJECTIVES: The objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. METHODS: Using data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. RESULTS: In both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (ß = -0.23, 95% CI: -0.41, -0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (ß = -0.19, 95% CI: -0.34, -0.051). There were no reliable differences in effect by fetal sex. DISCUSSION: The findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.

Calcaneal Osteosarcoma: A Rare Instance in Adolescent Patient.

Introduction: Calcaneal osteosarcoma is extremely uncommon, accounting for <1% of all osteosarcomas. They typically exhibit swelling and chronic heel pain and are frequently clinically misdiagnosed as traumatic or inflammatory process. Case Report: We report a case of a 19-year-old girl with calcaneal osteosarcoma who initially complained of heel pain that was refractory to analgesic medications over a period of 4 months. Conclusion: The case highlights the importance of early diagnosis and management of osteosarcoma in patients with chronic heel pain and also highlights the importance of considering osteosarcoma as a differential diagnosis in adolescents who present with chronic heel pain, despite the rarity of the condition.

Quality-Adjusted Time without Symptoms or Toxicity: Analysis of Axicabtagene Ciloleucel versus Standard of Care in Patients with Relapsed/Refractory Large B Cell Lymphoma.

The quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology provides a comprehensive framework for treatment comparison that partitions survival time into distinct health states reflecting both treatment toxicity and disease progression. ZUMA-7 (ClinicalTrials.gov identifier NCT03391466), a phase 3 randomized open-label multicenter study, was conducted to evaluate the efficacy of axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T cell therapy, compared with standard of care (SOC) involving platinum-based salvage chemotherapy with autologous stem cell transplantation (ASCT) consolidation as a second-line treatment for relapsed/refractory (R/R) large B cell lymphoma (LBCL), and met its primary endpoint of improved event-free survival (EFS). We aimed to use the Q-TWiST method to compare the quality-adjusted survival of R/R LBCL patients treated with axi-cel and those treated with SOC who were enrolled in ZUMA-7. The preplanned analysis of overall survival (OS) was partitioned into 3 mutually exclusive health states: time with grade ≥3 adverse events before the event as defined in the EFS analysis (TOX), time without severe toxicity before the event (TWiST), and time after the event (REL). Q-TWiST was computed as a weighted sum of mean TOX, TWiST, and REL values multiplied by state-specific quality of life (QoL) utility scores. Q-TWiST was evaluated in the intention-to-treat cohort at median follow-up. A relative Q-TWiST gain of 10% was deemed "clinically important" and a gain of ≥15% was deemed "clearly clinically important" based on established categorization. Sensitivity analyses with follow-up ranging from 3 months to the maximum follow-up and subgroup analyses by age and R/R status were explored. At a median follow-up of 23.5 months, the axi-cel cohort showed a significantly longer time without severe toxicity compared with the SOC cohort, with a mean TWiST duration of 11.18 months versus 5.39 months, respectively. The mean TOX was 1.16 months versus .74 months, and mean REL was 6.02 months versus 10.66 months. Quality-adjusted survival was significantly longer with axi-cel by 3.7 months (95% CI, 2.3 to 5.2 months), representing a relative gain of 21.9%. This was reflected across all subgroups, with estimated Q-TWiST gains of 3.1 months (95% CI, 1.5 to 4.9 months) for patients age <65 years, 5.2 months (95% CI, 2.4 to 7.9 months) for those age ≥65 years, 3.2 months (95% CI, 1.4 to 4.9 months) for those with primary refractory disease, 9.1 months (95% CI, 3.9 to months 13.5) for those who relapsed within 6 months, and 4.1 months (95% CI, 1.1 to 7.1 months) for those who relapsed between 6 and 12 months. The Q-TWiST gain for axi-cel also was statistically significant across follow-up durations, increasing from .2 month (95% CI, .1 to .3 month) at a 3-month follow-up to 4.9 months (95% CI, 2.4 to 7.8 months) at the maximum follow-up of 37.7 months. Axi-cel was associated with a statistically significant and "clearly clinically important" gain in quality-adjusted survival, regardless of the relative decline in QoL associated with treatment toxicity, disease progression, or additional cancer treatment. This finding adds to the existing evidence supporting a benefit for axi-cel as a second-line treatment for patients with R/R LBCL.