Background and Objectives: Risk stratification tools for febrile neutropenia exist but are infrequently utilized by emergency physicians. Procalcitonin may provide emergency physicians with a more objective tool to identify patients at risk of decompensation. Materials and Methods: We conducted a retrospective cohort study evaluating the use of procalcitonin in cases of febrile neutropenia among adult patients presenting to the Emergency Department compared to a non-neutropenic, febrile control group. Our primary outcome measure was in-hospital mortality with a secondary outcome of ICU admission. Results: Among febrile neutropenic patients, a positive initial procalcitonin value was associated with significantly increased odds of inpatient mortality after adjusting for age, sex, race, and ethnicity (AOR 9.912, p < 0.001), which was similar, though greater than, our non-neutropenic cohort (AOR 2.18, p < 0.001). All febrile neutropenic patients with a positive procalcitonin were admitted to the ICU. Procalcitonin had a higher sensitivity and negative predictive value (NPV) in regard to mortality and ICU admission for our neutropenic group versus our non-neutropenic control. Conclusions: Procalcitonin appears to be a valuable tool when attempting to risk stratify patients with febrile neutropenia presenting to the emergency department. Procalcitonin performed better in the prediction of death and ICU admission among patients with febrile neutropenia than a similar febrile, non-neutropenic control group.

[This corrects the article DOI: 10.1017/cts.2023.142.].

Objectives: To identify patient characteristics and treatment factors of patients presenting to the emergency department (ED) with cancer-related pain that may affect patient outcomes. Methods: We conducted a retrospective cohort study to evaluate adult patients with active cancer, who presented to the ED with a chief complaint of pain between June first, 2012 and January first, 2016. We utilized multivariable logistic regression to evaluate the association of several exposure variables, including disease and demographic characteristics, primary pain site, and treatment methods, on ED disposition and revisit rate. Results: We included 483 patients with active cancer with a chief complaint of pain. Patients with severe pain on arrival tended to be younger than those who did not present with severe pain (median: 58 vs 62 respectively, OR 8.0 p < 0.01). Patients with high ECOG scores (3-4) with severe pain on arrival (≥7 out of 10) had less improvement in their pain than the rest of our cohort (OR 8.4, p < 0.01). Also, those with musculoskeletal pain had significantly less improvement in reported pain than all other pain types (delta pain -2.1 vs -3.4, OR 2.3, p = 0.025) Long delays in initial analgesic administration were associated with increased rates of subsequent admission (OR 3.4) [p = 0.014]. Although opioid analgesics led to greater decreases in pain than non-opioid analgesics, patients treated with opioids were more likely to be admitted (43% vs 34.5% AOR 1.51, p = 0.048). Conclusion: Our study showed that delays in analgesic administration, poor functional status, and the presence of musculoskeletal (MSK) pain significantly influenced outcomes for this patient cohort. These findings suggest the development of specific protocols and tools to address cancer-related pain in the ED may be necessary.

Orbital metastases are a rare but life-altering complication in cancer. Most commonly seen in breast cancer, metastases to the optic nerves or extraocular muscles can have a devastating impact on visual acuity and quality of life. Hormone receptor status plays a central role in metastatic breast cancer treatment, with endocrine therapy often representing first-line therapy in hormone-receptor-positive cancers. Staging and treatment response evaluation with positron emission tomography (PET) computed tomography (CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) is limited by high physiologic uptake in the intracranial and intraorbital compartments. Thus, traditional staging scans with 18F-FDG PET/CT may under-detect intraorbital and intracranial metastatic disease and inaccurately evaluate active metastatic disease burden. In comparison, 18F-fluoroestradiol (18F-FES) is a novel estrogen-receptor-specific PET radiotracer, which more accurately assesses the intracranial and intraorbital compartments in patients with estrogen-receptor-positive (ER+) cancers than 18F-FDG, due to lack of physiologic background activity in these regions. We present two cases of breast cancer patients with orbital metastases confirmed on MR imaging who underwent PET/CT imaging with 18F-FES and 18F-FDG. Multimodality imaging with 18F-FES PET/CT offers higher detection sensitivity of orbital metastases, compared with traditional 18F-FDG PET/CT imaging, and can improve the assessment of treatment response in patients with estrogen-receptor-positive (ER+) cancers.

Purpose

Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes.

Methods

Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes.

Results

Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS (P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance.

Conclusion

Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

Purpose

ROR1 and ROR2 are Type 1 tyrosine kinase-like orphan receptors for Wnt5a that are associated with breast cancer progression. Experimental agents targeting ROR1 and ROR2 are in clinical trials. This study evaluated whether expression levels of ROR1 or ROR2 correlated with one another or with clinical outcomes.

Methods

We interrogated the clinical significance of high-level gene expression of ROR1 and/or ROR2 in the annotated transcriptome dataset from 989 patients with high-risk early breast cancer enrolled in one of nine completed/graduated/experimental and control arms in the neoadjuvant I-SPY2 clinical trial (NCT01042379).

Results

High ROR1 or high ROR2 was associated with breast cancer subtypes. High ROR1 was more prevalent among hormone receptor-negative and human epidermal growth factor receptor 2-negative (HR-HER2-) tumors and high ROR2 was less prevalent in this subtype. Although not associated with pathologic complete response, high ROR1 or high ROR2 each was associated with event-free survival (EFS) in distinct subtypes. High ROR1 associated with a worse EFS in HR + HER2- patients with high post-treatment residual cancer burden (RCB-II/III) (HR 1.41, 95% CI = 1.11-1.80) but not in patients with minimal post-treatment disease (RCB-0/I) (HR 1.85, 95% CI = 0.74-4.61). High ROR2 associated with an increased risk of relapse in patients with HER2 + disease and RCB-0/I (HR 3.46, 95% CI = 1.33-9.020) but not RCB-II/III (HR 1.07, 95% CI = 0.69-1.64).

Conclusion

High ROR1 or high ROR2 distinctly identified subsets of breast cancer patients with adverse outcomes. Further studies are warranted to determine if high ROR1 or high ROR2 may identify high-risk populations for studies of targeted therapies.

Background

Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer.

Patients and methods

Eligible patients had locally advanced, unresectable, or metastatic HER2^- breast cancer with Eastern Cooperative Group performance status of 0-2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m² IV.

Results

Study patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response.

Conclusion

The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted.

Trial registration

NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.

Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician's direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician's choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50-0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50-0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival.

The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%-37%), hormone receptor (HR)-positive/HER2-negative (14%-28%), and triple-negative breast cancer (TNBC) (27%-47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.