Receptor-Targeted Peptide Conjugates Based on Diphosphines Enable Preparation of 99mTc and 188Re Theranostic Agents for Prostate Cancer.

Benchtop 99Mo/99mTc and 188W/188Re generators enable economical production of molecular theranostic 99mTc and 188Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99mTc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99mTc and 188Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99mTc and 188Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99mTc/188Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99mTc and 188Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [99mTc]Tc, [188Re]Re). All 99mTc/188Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99mTc/188Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99mTc/188Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177Lu radiopharmaceuticals or PET/CT infrastructure.

Family health beliefs and cascade genetic testing in Asian families with hereditary cancer risk: "Okay, now what?"

The limited literature on Asian family communication of hereditary cancer risk and cascade genetic testing for pathogenic variants (PVs) in BRCA1 and BRCA2 has reported that Asian patients have selective communication of test results and lower cascade testing rates. To better understand the factors that impact communication and cascade testing in Asian families, we conducted an in-depth qualitative study guided by the Health Belief Model. Participants with heterozygous PVs in ATM, BRCA1, BRCA2, CHEK2, or PALB2, who identified their family's origins to an Asian country, were recruited from the Stanford Cancer Genetics Research Database in October-November 2021. Utilizing a constructivist approach, we conducted sixteen semi-structured interviews around family communication and cascade genetic testing. The research team analyzed the transcript data using a reflexive thematic approach. Extensive discussions between the research team resulted in three primary themes presented in this paper: (1) the role of family health beliefs in cascade genetic testing, (2) changes in communication as a result of genetic testing, and (3) genetics providers' role in supporting family discussions on cascade genetic testing. Certain health beliefs, such as perceived susceptibility to cancer and self-efficacy to take action, were co-created by family members and these shared beliefs influenced decisions about genetic testing, family communication, and family support during the cascade genetic testing process. Participants shared strategies for how genetics providers can prepare Asian patients for more effective conversations with relatives and better address potential testing barriers by tailoring information and providing anticipatory guidance. This study represents an important contribution to the literature about cascade testing among an underrepresented group. Shared family health beliefs about genetic testing may be particularly relevant for this community and these findings can inform strategies to increase cascade genetic testing in Asian families.

Prevalence of Duffy null and its impact on hydroxyurea in young children with sickle cell disease in the United States.

Consistent with studies showing a high prevalence of the Duffy null phenotype among healthy Black Americans, this retrospective study found that Duffy null was present in >75% of a young and contemporary cohort of children with sickle cell disease (SCD) in the United States. Despite the potential for this phenotype to impact absolute neutrophil counts, hydroxyurea (HU) dosing, and outcomes, it was not associated with being prescribed a lower HU dose or having increased acute SCD visits early in the HU treatment course. Future studies are needed to confirm these findings in older children with SCD.

Selection of radionuclide(s) for targeted alpha therapy based on their nuclear decay properties.

Targeted alpha therapy (TAT) is a promising form of oncology treatment utilising alpha-emitting radionuclides that can specifically accumulate at disease sites. The high energy and high linear energy transfer associated with alpha emissions causes localised damage at target sites whilst minimising that to surrounding healthy tissue. The lack of appropriate radionuclides has inhibited research in TAT. The identification of appropriate radionuclides should be primarily a function of the radionuclide's nuclear decay properties, and not their biochemistry or economic factors since these last two factors can change; however, the nuclear decay properties are fixed to that nuclide. This study has defined and applied a criterion based on nuclear decay properties useful for TAT. This down-selection exercise concluded that the most appropriate radionuclides are: 149 Tb, 211 At/ 211 Po, 212 Pb/ 212 Bi/ 212 Po, 213 Bi/ 213 Po, 224 Ra, 225 Ra/ 225 Ac/ 221 Fr, 226 Ac/ 226 Th, 227 Th/ 223 Ra/ 219 Rn, 229 U, 230 U/ 226 Th, and 253 Fm, the majority of which have previously been considered for TAT. 229 U and 253 Fm have been newly identified and could become new radionuclides of interest for TAT, depending on their decay chain progeny.

Burnout and Appreciation: A Cross-Sectional Study Assessing Preferences for Appreciation Among Oncology Clinicians.

PURPOSE: Feeling appreciated is related to increased well-being/reduced burnout. We developed a health care-specific appreciation assessment for clinicians, exploring what impactful appreciation looks like and whether it differs across a diverse provider population. METHODS: The cross-sectional study was conducted with a diverse oncology clinician population in academic medicine as part of a general well-being survey. A total of 28 different methods of appreciation were assessed for their impact on feeling appreciated. RESULTS: A total of 405 clinicians participated (response rate, 58%). No single method of appreciation showed high/low impact for everyone, although seven methods received high impact ratings from 60% or more, including inclusion in decision making (76%), private words of affirmation (64%), positive feedback about skills (63%), positive comments about clinical care from patients/families (62%), efforts to reduce daily frustrations (62%), signs of trust in medical skills (62%), and time for self-care (62%). The least impactful methods of appreciation describe public expression of accomplishments, leadership rounding, and awards but each still receive a rating of moderate/high impact from 33% of participants. CONCLUSION: Appreciation comes from many different places and takes on multiple forms, suggesting that making healthcare workers (HCWs) feel valued takes the efforts of colleagues, leaders, the system as well as patients. There exists no one perfect way of showing appreciation, and no one method is meaningless for all. The impact on feeling valued is primarily a function of the specific appreciation method and not the demographic/personal characteristics of the recipient. The findings highlight modifiable factors that-when intervened upon-can reduce burnout and address organization-level determinants of burnout impactfully.

Versatile Diphosphine Chelators for Radiolabeling Peptides with 99mTc and 64Cu.

We have developed a diphosphine (DP) platform for radiolabeling peptides with 99mTc and 64Cu for molecular SPECT and PET imaging, respectively. Two diphosphines, 2,3-bis(diphenylphosphino)maleic anhydride (DPPh) and 2,3-bis(di-p-tolylphosphino)maleic anhydride (DPTol), were each reacted with a Prostate Specific Membrane Antigen-targeted dipeptide (PSMAt) to yield the bioconjugates DPPh-PSMAt and DPTol-PSMAt, as well as an integrin-targeted cyclic peptide, RGD, to yield the bioconjugates DPPh-RGD and DPTol-RGD. Each of these DP-PSMAt conjugates formed geometric cis/trans-[MO2(DPX-PSMAt)2]+ (M = 99mTc, 99gTc, natRe; X = Ph, Tol) complexes when reacted with [MO2]+ motifs. Furthermore, both DPPh-PSMAt and DPTol-PSMAt could be formulated into kits containing reducing agent and buffer components, enabling preparation of the new radiotracers cis/trans-[99mTcO2(DPPh-PSMAt)2]+ and cis/trans-[99mTcO2(DPTol-PSMAt)2]+ from aqueous 99mTcO4- in 81% and 88% radiochemical yield (RCY), respectively, in 5 min at 100 °C. The consistently higher RCYs observed for cis/trans-[99mTcO2(DPTol-PSMAt)2]+ are attributed to the increased reactivity of DPTol-PSMAt over DPPh-PSMAt. Both cis/trans-[99mTcO2(DPPh-PSMAt)2]+ and cis/trans-[99mTcO2(DPTol-PSMAt)2]+ exhibited high metabolic stability, and in vivo SPECT imaging in healthy mice revealed that both new radiotracers cleared rapidly from circulation, via a renal pathway. These new diphosphine bioconjugates also furnished [64Cu(DPX-PSMAt)2]+ (X = Ph, Tol) complexes rapidly, in a high RCY (>95%), under mild conditions. In summary, the new DP platform is versatile: it enables straightforward functionalization of targeting peptides with a diphosphine chelator, and the resulting bioconjugates can be simply radiolabeled with both the SPECT and PET radionuclides, 99mTc and 64Cu, in high RCYs. Furthermore, the DP platform is amenable to derivatization to either increase the chelator reactivity with metallic radioisotopes or, alternatively, modify the radiotracer hydrophilicity. Functionalized diphosphine chelators thus have the potential to provide access to new molecular radiotracers for receptor-targeted imaging.

Implementing Digital Scribes to Reduce Electronic Health Record Documentation Burden Among Cancer Care Clinicians: A Mixed-Methods Pilot Study.

PURPOSE: To address shortcomings of human scribes (eg, turnover), clinicians are considering digital scribes (DSs). To our knowledge, to date, no study has assessed DS implementation or clinician user experience in cancer centers. We assessed the DS's feasibility, acceptability, appropriateness, usability and its preliminary association on clinician well-being in a cancer center. We also identified implementation facilitators and barriers to DS use. METHODS: Using a mixed-methods longitudinal pilot study design, we implemented a DS at a cancer center. Data collection included surveys at baseline and 1 month after DS use and a semistructured interview with clinicians. The survey assessed demographics, Mini Z (workplace stress and burnout), sleep quality, and implementation outcomes (feasibility, acceptability, appropriateness, and usability). The interview assessed how the DS was used and its impacts on workflows and recommendations for future implementations of the DS. We used paired t tests to assess differences in Mini Z and sleep quality measures over time. RESULTS: Across nine survey responses and eight interviews, we found that although feasibility scores were slightly lower than our cutoff point (15.2 v 16.0), clinicians rated the DS as marginally acceptable (16.0) and appropriate (16.3). Usability was considered marginally usable (68.6 v 68.0). Although the DS did not significantly improve burnout (3.6 v 3.9, P = .081), it improved perceptions of having sufficient documentation time (2.1 v 3.6, P = .005). Clinicians identified suggestions for future implementations, including training needs and usability improvements. CONCLUSION: Our preliminary findings suggest that DS implementation is marginally acceptable, appropriate, and usable among cancer care clinicians. Individualized training and on-site support may improve implementation.

Latinx attitudes, barriers, and experiences with genetic counseling and testing: A systematic review.

As genetics is increasingly used across clinical settings, there is a need to understand the impact and experiences of diverse patients. This review systematically examined research literature on Latinx experiences with genetic counseling and genetic testing (GC/GT) in the United States, synthesizing key themes and knowledge gaps pertaining to both patient experience and hypothetical scenarios. Findings were based on a systematic search, inclusion, and thematic analysis of 81 empirical peer-reviewed articles published from January 1990 to July 2019 pertaining to Latinx populations and GC/GT. Studies most commonly addressed Latinas' perspectives on GC/GT in prenatal settings or for hereditary breast and ovarian cancer (HBOC). Costs, referrals, and communication were significant barriers to accessing genetic services for many Latinx patients, particularly those with low English proficiency (LEP). Studies highlighted difficulties accessing and communicating in healthcare settings, and how medical context and prior experience with healthcare workers and institutions influenced GC/GT decision-making. Providers' implicit biases about Latinx patients negatively impacted their care and impeded communication. Despite low awareness of cancer GT, Latinx patients often reported interest in learning more about GC/GT or unmet needs for GT discussion and provider involvement. This systematic review identified areas where providers can take action to improve Latinx experiences with GC/GT. Clinicians should elicit and respond to patient preferences about shared decision-making. For patients with low numeracy or LEP, providers should consider tailored educational and communication techniques. Most studies focused on HBOC and prenatal testing, and Latinx patients are heterogeneous, leaving many research questions about Latinx experience with GT/GC in other clinical areas.

PSMA-targeted NIR probes for image-guided detection of prostate cancer.

Tumour-targeted near-infrared (NIR) optical imaging is an emerging tool for the detection of malignant tissues. This modality can be useful in both diagnosis and intraoperative visualisation, to help defining tumour margins and allow a more precise removal of all the cancerous mass during surgery. In this context, we have developed a series of NIR fluorescent probes that target the prostate-specific membrane antigen (PSMA), an established biomarker overexpressed in prostate cancer. Four new NIR imaging agents were prepared by conjugating the well-known urea-based PSMA targeting module to the NIR fluorophore Cy7.5, with linkers of 7, 10, 17 and 24 atoms. The affinity of each probe for PSMA was assessed through competitive binding and IC50 measurement in prostate cancer cells, using a previously reported PSMA-targeted NIR probe (i.e. PSMA-IRDye800CW) as reference. The NIR probe PSMA-Cy7.5_2 demonstrated a high affinity for PSMA (i.e. IC50 = 58.8 nM) and was further studied in mouse xenograft models of prostate cancer, to assess its ability to image PSMA positive tumour tissues. While PSMA-Cy7.5_2 out-performed PSMA-IRDye800CW in vitro, its tumour accumulation in vivo was not as evident. Further micellar aggregation studies indicated that the relatively higher hydrophobic property of PSMA-Cy7.5_2 may lower its bioavailability and tissue distribution following systemic injection, limiting its ability of targeting PSMA tumour in vivo. Nevertheless, the excellent binding capability of PSMA-Cy7.5_2 renders this probe a valid lead for further structural optimisation to develop imaging analogues with high affinity and specificity for PSMA, as required for effective NIR fluorescence-guided applications pre-clinically and clinically.

Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study.

OBJECTIVES: There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. METHODS: The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2-5) and high grade (≥G3) infections. RESULTS: In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2-8), 23.4% of patients experienced ≥1 any grade (G2-5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16-75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (

Efficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset.

Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1-18.6 mo), median age (IQR) was 69 years (61-77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2-4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3-3). Median (IQR) number of IsaPomDex cycles administered was 7 (3-13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65-74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.

Embodied risk for families with Li-Fraumeni syndrome: Like electricity through my body.

INTRODUCTION: Experiences of illness change the physical body and embodiments, or the ways in which the world and the self are known through the body. When illness is anticipated, such as with inherited cancer predisposition syndromes, risk becomes embodied and shared in family groups. Embodied risk is experienced whether or not symptoms have manifested. To examine how individuals and families with genetic risk experience the world and understand their disease through their bodies, we employ Li-Fraumeni syndrome (LFS) as an exemplar. LFS is a rare, genetic, cancer predisposition syndrome with nearly 100% lifetime cancer risk starting from birth, limited opportunities for prevention, rigorous screening protocols, and early mortality. METHODS: Forty-five families, including 117 individuals aged 13-81 years, enrolled in the National Cancer Insitute's LFS study (NCT01443468) completed 66 open-ended interviews regarding LFS experiences. An interdisciplinary team used modified grounded theory to explore physical aspects of living with LFS in psychosocial contexts. FINDINGS: The physicality of living with LFS included constant monitoring of LFS bodies across the family to identify physical change that might indicate carcinogenesis. Cancer screening, risk reduction, and treatment acted as dually protective and invasive, and as an unavoidable features of LFS. Connections between family members with similar embodiments normalized aesthetic changes and supported coping with visible markers of difference. In some circumstances, participants objectified the body to preserve the self and important relationships. In others, intense pain or loss created thresholds beyond which the self could no longer be separated from the body to support coping. DISCUSSION: This paper focuses on Li-Fraumeni syndrome, a familial condition with a well-established genetic identity in which the body-self is experienced in relation to important others, to medical imaging, and to historical experiences with cancer. We expand on theories of embodied risk and inter-embodiment to describe experiences across disease trajectories, with attention to division and union between body, self, and other.

The value of magnetic resonance imaging-ultrasound fusion targeted biopsies for clinical decision-making among patients with previously negative transrectal ultrasound biopsy and persistent prostate-specific antigen elevation.

INTRODUCTION: Targeted biopsy approaches have been shown to increase the detection of clinically significant prostate cancer (csPCa) within index prostate lesions. We report our initial experience with magnetic resonance imaging-ultrasound fusion biopsies (MRI-TB) in a population of men who had a previously negative transrectal ultrasound (TRUS) biopsy, persistent prostate-specific antigen (PSA) elevation, and ongoing suspicion of PCa. Patients were followed prospectively to assess for changes in clinical management following targeted biopsy. METHODS: We prospectively followed the first 122 patients undergoing MRI-TB at our institution. All men had clinical suspicion of PCa, prior negative TRUS biopsies, and persistent PSA elevation. A total of 177 index lesions were identified on multiparametric MRI and reviewed using the Prostate Imaging Reporting and Data System (PI-RADS) v2 scoring system. Lesions classified as PI-RADS ≥3 received targeted biopsy. Biopsy-naive patients and those on active surveillance were excluded. The primary outcome was detection rate of csPCa, defined as International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2. Multivariate analysis was used to determine predictors of csPCa on fusion biopsy. RESULTS: Prior to fusion biopsy, patients had a mean of 17.9±8.6 negative core biopsies per patient and a median PSA of 9.5 (standard deviation [SD] 6.2) ng/nl. MRI-TB resulted in diagnosis of csPCa in 42/122 (34.4%) patients. Clinically significant PCa was found in eight (13.1%), 14 (21.9%), and 25 (48.1%) of PI-RADS 3, 4, and 5 lesions, respectively. The location of csPCa was within the peripheral zone (55.3%), transitional zone (40.4%), and central zone (8.5%). Clinical outcomes of patients with newly diagnosed csPCa show 4.8%, 57.1%, and 38.1% receiving active surveillance, radiation treatment, and radical prostatectomy, respectively. Predictors for csPCa were presence of PI-RADS 5 lesions, age, length of time from MRI to biopsy, and smaller prostate volumes. CONCLUSIONS: MRI-TB yields high detection rates for csPCa in men with elusive PSA elevation and frequently guides a change in clinical management. Clinical decision-making based on MRI findings and PI-RADS lesion scores are best informed by an understanding of institutional reporting patterns.

Chemotherapy-induced thrombocytopenia in Ewing sarcoma: Implications and potential for romiplostim supportive care.

BACKGROUND: Maintaining dose-dense, interval-compressed chemotherapy improves survival in patients with Ewing sarcoma but is limited by myelosuppression. Romiplostim is a thrombopoietin receptor agonist that may be useful in the treatment of chemotherapy-induced thrombocytopenia (CIT). METHODS: Patients aged between 3 and 33 years with Ewing sarcoma from 2010 to 2020 were reviewed. CIT was defined as a failure to achieve 75,000 platelets per microliter by day 21 after the start of any chemotherapy cycle. Fisher's exact test was used for univariate analysis and Pearson's correlation coefficient was used for the association between continuous variables. RESULTS: Twenty-seven out of 42 patients (64%) developed isolated CIT, delaying one to four chemotherapy cycles per patient. CIT occurred during consolidation therapy in 24/27(88.9%) and with ifosfamide/etoposide cycles in 24/27 (88.9%). Univariate analysis failed to identify risk factors for CIT. The use of radiation approached significance (p-value = .056). Ten patients received romiplostim. The median starting dose was 3 µg/kg (range 1-5). Doses were escalated weekly by 1-2 to 4-10 µg/kg and continued throughout chemotherapy. A higher romiplostim dose was associated with a higher change in average platelet counts from baseline, r = .73 (p = .04). No romiplostim-related adverse events were identified aside from mild headache. CONCLUSIONS: CIT is the primary reason for the inability to maintain treatment intensity in Ewing sarcoma. The concurrent use of romiplostim with chemotherapy was safe and feasible, and efficacy was associated with higher romiplostim doses.

Disease- and Therapy-Specific Impact on Humoral Immune Responses to COVID-19 Vaccination in Hematologic Malignancies.

Coronavirus disease-19 (COVID-19) vaccine response data for patients with hematologic malignancy, who carry high risk for severe COVID-19 illness, are incomplete. In a study of 551 hematologic malignancy patients with leukemia, lymphoma, and multiple myeloma, anti-SARS-CoV-2 spike IgG titers and neutralizing activity were measured at 1 and 3 months from initial vaccination. Compared with healthy controls, patients with hematologic malignancy had attenuated antibody titers at 1 and 3 months. Furthermore, patients with hematologic malignancy had markedly diminished neutralizing capacity of 26.3% at 1 month and 43.6% at 3 months, despite positive seroconversion rates of 51.5% and 68.9% at the respective time points. Healthy controls had 93.2% and 100% neutralizing capacity at 1 and 3 months, respectively. Patients with leukemia, lymphoma, and multiple myeloma on observation had uniformly blunted responses. Treatment with Bruton tyrosine kinase inhibitors, venetoclax, phosphoinositide 3-kinase inhibitors, anti-CD19/CD20-directed therapies, and anti-CD38/B-cell maturation antigen-directed therapies substantially hindered responses, but single-agent immunomodulatory agents did not. Significance: Patients with hematologic malignancy have compromised COVID-19 vaccine responses at baseline that are further suppressed by active therapy, with many patients having insufficient neutralizing capacity despite positive antibody titers. Refining vaccine response parameters is critical to guiding clinical care, including the indication for booster vaccines, for this vulnerable population.See related article by Tamari et al., p. 577. This article is highlighted in the In This Issue feature, p. 549.

Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy.

Cellular therapies including allogeneic hematopoietic cell transplant (allo-HCT) and autologous hematopoietic cell transplant (auto-HCT) and chimeric antigen receptor (CAR) T-cell therapy render patients severely immunocompromised for extended periods after therapy, and data on responses to COVID-19 vaccines are limited. We analyzed anti-SARS-CoV-2 spike IgG Ab (spike Ab) titers and neutralizing Ab among 217 recipients of cellular treatments (allo-HCT, n = 149; auto-HCT, n = 61; CAR T-cell therapy, n = 7). At 3 months after vaccination, 188 patients (87%) had positive spike Ab levels and 139 (77%) had positive neutralization activity compared with 100% for both in 54 concurrent healthy controls. Time from cellular therapy to vaccination and immune recovery post-cellular therapy were associated with response. Vaccination against COVID-19 is an important component of post-cellular therapy care, and predictors of quantitative and qualitative response are critical in informing clinical decisions about optimal timing of vaccines and the requirement for booster doses. Significance: Identifying predictors of response to vaccination against SARS-CoV-2 in patients following cellular therapy is critical to managing this highly vulnerable patient population. To date, this is the most comprehensive study evaluating quantitative and qualitative responses to vaccination, providing parameters most predictive of response and potentially informing booster vaccination strategies.See related article by Chung et al., p. 568. This article is highlighted in the In This Issue feature, p. 549.

Family Identity and Roles in the Context of Li-Fraumeni Syndrome: "No One's Like Us Mutants".

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome in which individuals have a significantly increased risk of developing multiple cancers throughout the life span. An LFS diagnosis may shift the individual's sense of self and tolerance of cancer risk as they engage in cancer screening and cancer prevention activities. This study examined the impact of family identity on health decision making, communication, and role function. Forty-five families completed one or more interviews during an annual, protocol-specific cancer screening study. An interdisciplinary team analyzed 66 interviews using interpretive description and modified grounding theory. Thematically, identity emerged as an evolving construct regarding self and/or family, embedded in historical and ongoing experiences with LFS. Notions of individual and shared family identities guided decision making related to healthcare and influenced interpersonal communication and role function between supportive networks and families. Alignment between individual, family, and generational identities may shape engagement in genetic testing, risk management, and family life. Medical teams that are unequipped to address the psychosocial challenges that LFS populations face may include mental health professionals on interprofessional care teams to navigate risk management and consequential familial conflict.

An overview of nuclear medicine research in the UK and the landscape for clinical adoption.

BACKGROUND AND OBJECTIVES: Nuclear medicine contributes greatly to the clinical management of patients and experimental medicine. This report aims to (1) outline the current landscape of nuclear medicine research in the UK, including current facilities and recent or ongoing clinical studies and (2) provide information about the available pathways for clinical adoption and NHS funding (commissioning) of radiopharmaceuticals. METHODS: Evidence was obtained through database searches for UK-based nuclear medicine clinical studies and by conducting a questionnaire-based survey of UK radiopharmaceutical production facilities. A recent history of clinical commissioning, either through recommendations from the National Institute for Health and Care Excellence (NICE) or through NHS specialised services commissioning, was compiled from publicly available documents and policies. RESULTS: The collected data highlighted the UK's active nuclear medicine research community and recent investment in new facilities and upgrades. All commissioning routes favour radiopharmaceuticals that have marketing authorisation and since 2017 there has been a requirement to demonstrate both clinical and cost-effectiveness. Whilst radiopharmaceuticals for molecular radiotherapy are well suited to these commissioning pathways, diagnostic radiotracers have not historically been assessed in this manner. CONCLUSIONS: We hope that by collating this information we will provide stimulus for future discussion and consensus statements around this topic.