Lemuel Shattuck Hospital

We present the case of a patient with bilateral distal humerus osteonecrosis following chemoradiation for lymphoma. Treatment consisted of a right total elbow arthroplasty with a distal humerus megaprosthesis and a left custom-made distal humerus hemiarthroplasty, replacing exclusively the humeral articular cartilage while preserving the native medial and lateral humeral columns. By using a custom implant of this design, we were able to avoid the weight-bearing and lifting restrictions to which patients have to adhere following a typical total elbow arthroplasty. Thus, we were able to preserve weight-bearing capacity in the dominant arm of the patient, which she required to act as a caregiver to a disabled family member. The case was complicated by a concurrent high radial nerve palsy which was treated by nerve decompression and transfers of tendons and nerves. Ultimately, bilateral upper extremity function was good with negligible pain at 2 years of follow-up. In conclusion, this case demonstrates the value of a combined orthoplastic approach and custom implants in successfully reconstructing complex upper extremity defects such as bilateral elbow joint osteonecrosis.

Presence of intravenous contrast on computed tomography (CT) scans is often unreliably documented, especially in large research datasets. FALCON is an open-access fully automated deep learning model enabling large-scale intravenous contrast detection and body part classification for CT scans of the head and neck (HN), chest, abdomen, and pelvis (AP). This study used six independent datasets consisting of 3138 CT scans of the HN, chest, and AP of 3126 patients from five institutions between 1996 and 2023 to train and validate four CNN models for intravenous contrast detection and body part classification. The ground truth of intravenous contrast presence was verified by a radiologist. We used ResNet9 network architecture and integrated the four models into a graphical user interface. We assessed FALCON's performance with F1 scores and compared FALCON's annotation time to manual annotation by human experts. In the external test set containing 1348 scans, the F1 score for intravenous contrast detection was 99.4% (95%CI: 98.8, 99.9) for HN CT, 98.3% (95%CI: 96.9, 99.5) for chest CT, and 98.1% (95%CI: 96.9, 99.1) for AP CT. The F1 score for body part classification alone on unseen data was 100% for HN, chest, and AP CT. Compared to human experts, annotation of a single scan with FALCON required 1.3 s vs. 21 s for HN CT, 1.8 s vs. 33 s for chest CT, and 3.7 s vs. 1.6 s for AP CT. The open-access FALCON model ( https://github.com/FintelmannLabDevelopmentTeam/Falcon ) quickly and reliably detects intravenous contrast and classifies body part on CT scans.

Despite the effectiveness of [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC), hematologic toxicity remains a concern, particularly in patients with bone metastases. This study evaluated whether the extent, intensity, and heterogeneity of bone disease on pretreatment PSMA-PET/CT were associated with hematologic toxicity, PSA response, and overall survival (OS) in mCRPC patients treated with [177Lu]Lu-PSMA-617. This retrospective study included 96 mCRPC patients who underwent pretreatment PSMA-PET/CT and received standard-of-care [177Lu]Lu-PSMA-617. Hematologic toxicity, PSA responses, and OS were analyzed in relation to quantitative PET parameters, including tumor volume, SUVmean, and heterogeneity of PSMA uptake in bone metastases. Clinically significant hematologic toxicity occurred in 19 patients (19.8%). Treatment discontinuation was more likely in those with a significantly higher (p = 0.007) percentage of total bone volume with PSMA-avid disease (median 28% vs. 1.7%). Those requiring dose delays or reductions (median 21% vs. 1.5%), blood transfusions (median 21% vs. 1.4%), and platelet transfusions (median 32% vs. 1.8%) also exhibited higher median percentages of total bone volume involvement (all p < 0.01). Patients with more heterogeneous PSMA uptake had lower PSA50 response rates than those with more homogeneous uptake (30.3% vs. 64.5%, p = 0.002). A > 50% difference between PSMA-low and PSMA-high bone disease was associated with significantly shorter OS (p < 0.001). Extensive PSMA-avid bone involvement was associated with increased hematologic toxicity in mCRPC treated with [177Lu]Lu-PSMA-617. Greater heterogeneity in PSMA uptake correlated with lower PSA50 response and OS but not hematologic toxicity. Careful patient selection and monitoring are needed, particularly in those with widespread bone disease.

BackgroundThe substantial health burdens and prevalence of cancer-related pain both during and after treatment underscore the need for expanded access to cancer pain specialists and therapeutic pain treatments. Despite growing demand, cancer pain specialists face substantial barriers to providing effective care.ObjectiveThis exploratory study sought to characterize perspectives from a small group of international pain experts to examine patterns of utilization and perceived accessibility of interventional therapies across cancer types and clinical practice settings.MethodsAn international, anonymous survey of cancer pain experts, identified via rigorous definition criteria, was conducted using the Qualtrics platform. The survey evaluated eight cancer-related pain categories: head and neck cancer, pleural and rib-based lung cancer, pancreatic cancer, pelvic cancer, lumbosacral spine cancer, extremity cancer, chemotherapy-induced peripheral neuropathy, and bone metastases. Respondents were asked to indicate which treatments they currently use for each type of cancer and which they would use if they had access to them.ResultsCancer pain experts reported limited access to procedures with greater complexity. Some procedures had substantial variability in use and accessibility, specifically SCS, ITDD, permanent PNS, and nucleus tractus cordotomy. Complementary and alternative therapies were desirable but largely unavailable, particularly in academic settings.ConclusionDespite the growing need for cancer pain management, specialists continue to face substantial barriers to delivering effective care. This exploratory survey of cancer pain experts identified patterns of reported use and access limitations for therapies across cancer types and practice settings. These findings suggest a relationship between procedural complexity and access barriers, with utilization and availability shaped by institutional resources and practice settings.

Metastatic castration-resistant prostate cancer/PCa (mCRPC) is a clinically advanced form of PCa that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing resistance to taxanes, currently the first-line chemotherapy for mCRPC. Clofazimine (CLF) is a potential immunomodulator drug that is FDA-approved for the treatment of leprosy. Recently, using in vitro, in vivo, and ex vivo models, we established the efficacy of CLF in chronic myeloid leukemia and multiple myeloma. Here, we demonstrate that CLF is effective as a single agent and in combination with taxanes in a panel of cell lines representing the diversity of CRPC patients. Using a microfluidic assay, we showed the impact of CLF on cancer cell migration and metastatic potential. Further, we also found that CLF reduces ALDH activity—a marker for cancer ‘stem-like’ cells (CSCs), a subtype of cancer cells with self-renewal and differentiation capacities (epithelial-to-mesenchymal transdifferentiation/EMT). Bulk and single-cell RNAseq followed by functional validation and in silico analysis showed that CLF treatment is associated with apoptosis, ER stress, oxidative phosphorylation, and mitochondrial dysfunction. Most importantly, CLF modulates the expression of several non-coding RNAs, including MALAT1 and NEAT1, that are linked to tumor cell proliferation, cell migration, and drug resistance.

ObjectiveThe success of a randomized controlled trial (RCT) depends, in part, on the willingness to participate (WTP) of eligible subjects. Prospective preference assessments (PPA) offer insights into future RCT enrollment by evaluating eligible individuals’ WTP in the RCT. We sought to summarize the methods and findings of published PPAs and to compare the WTP estimates of published PPAs to the actual enrollment rates from these trials.DesignWe performed a systematic literature search using PubMed for studies that assessed eligible participants’ WTP in a hypothetical trial. We abstracted sample size, proposed interventions, WTP response options, WTP percentage, presence of qualitative analyses, and assessment of trial feasibility from each publication. We defined WTP as a response of “probably” or “definitely” willing in the PPA; in sensitivity analyses, we included only “definitely” willing responses. We searched for registered and published RCTs connected to each PPA and extracted enrollment data from the corresponding trial publications where available.ResultsWe identified 40 PPAs. The median WTP across all PPAs was 54.9 ​% (range: 13 ​%–92.4 ​%), and 42.1 ​% (range: 7 ​%–90.2 ​%) when including only “definitely willing” responses. We found ten registered RCTs; five are completed and one is ongoing. Four PPAs with a RCT provided both “definitely willing” and “total willing” estimates. In three of these four RCTs, the actual enrollment fell between the “definitely willing” and “total willing” PPA estimates.Conclusion“Definitely willing” and “total willing” findings in a PPA may provide useful upper and lower boundaries on participation for future trial planning.

To determine malignancy rate of adrenal nodules in patients with a history of cancer and identify factors predictive of adrenal metastases. This Institutional Review Board-approved, retrospective study was performed 1/1/2010-12/31/2020 at an academic health system. Cancer registry data and natural language processing identified patients with a history of extra-adrenal malignancy who had undergone contrast-enhanced abdominal CT or MRI and had adrenal nodules ≥ 1cm. A power calculation based on previously published prevalence of malignancy in adrenal nodules determined the minimum number of patients. The reference standard used for diagnosis was pathology when available, or imaging follow-up ≥ 1 year. Cancer type, presence/absence of extra-adrenal metastatic disease on index scan, and size of the adrenal nodule were extracted from the electronic health record. These factors were correlated with adrenal nodule outcome (benign or metastatic) using univariate and multivariable logistic regression analyses. The cohort included 420 patients (219 female; mean age 71.4 years [standard deviation 11.1]). Overall metastatic adrenal nodule rate was 15.7% (66/420). Patients with extra-adrenal metastatic disease were more likely to have metastatic adrenal nodules compared to those with an isolated adrenal nodule (24.5% [37/151] vs. 10.8% [29/269]; p ≤ 0.001). Adrenal metastases were most common in patients with melanoma (50%, 10/20) and lung cancer (32%, 24/75). Metastatic rate increased with nodule size 2-4cm (Odds Ratio [OR] 1.98) and > 4cm (OR 3.25). In patients with an isolated adrenal nodule, primary malignancy (lung cancer: OR 10.80; melanoma: OR 32.91) and size (2-4cm: OR 5.14, > 4cm: OR 9.69) were associated with increased risk of metastases. In a cohort of patients with a history of any type of malignancy, almost 90% of isolated adrenal nodules were benign. However, a history of lung cancer, melanoma, or lesion size ≥ 2cm significantly increased the risk of adrenal metastases.