Faculty Bibliography

BACKGROUND:Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPC) patients typically exhibit reduced rates of second primary malignancies (SPMs) compared to HPV-negative head and neck cancer patients. While HPV+ OPC patients may be predisposed to SPMs in HPV-associated anatomical sites, the metachronous presentation of an HPV+ OPC and subsequent glioblastoma multiforme (GBM) has not been previously documented. CASES/METHODS:We present two cases of HPV+ OPC patients who developed GBMs within a short period after definitive therapy. METHODS:Comprehensive whole exome sequencing (WES) was performed on paired GBM, oropharyngeal, and matched normal tissues from two HPV+ OPC patients who developed GBMs within a short period after definitive therapy, with the goal of identifying shared somatic and germline variants. Bioinformatic analyses included variant calling, annotation, and pathway enrichment. RESULTS:WES revealed a shared CEP104 missense mutation among both oropharyngeal tumors as well as a potential KIR2DL4 germline variant in the second patient, suggesting a possible role for disrupted NK cell immunity in driving these cancers. CONCLUSION/CONCLUSIONS:Although these cases were likely random events, they illustrate the diagnostic and therapeutic challenges of GBM following HPV+ OPC and underscore the importance of personalized genomic assessment in HPV+ OPC survivors, who may develop non-head and neck SPMs unrelated to field cancerization.

IMPORTANCE/OBJECTIVE:The rising incidence of HPV-positive oropharynx cancer (HPV-OPC) underscores the need for treatment strategies that maintain disease control while minimizing long-term toxicity. This study reports the long-term follow-up of de-escalation in poor prognosis HPV-OPC, providing critical data for future studies. OBJECTIVE:To evaluate long-term outcomes in patients with locally advanced HPV-OPC treated with induction chemotherapy (IC) followed by reduced-dose chemoradiation (rdCRT). We hypothesized that de-escalated radiation therapy after IC would be non-inferior to standard-dose CRT (sdCRT). DESIGN/METHODS:Two sequential clinical trials; Quarterback (QB) 1: phase III randomized control trial, QB 2: phase II non-randomized trial; patient accrual conducted between December 2012 and February 2022; final data cutoff April 2025. Median follow-up (IQR): 88.5 (64.6-118.2) months. SETTING/METHODS:Single-institution academic center. PARTICIPANTS/METHODS:62 patients with HPV-OPC were screened. 47 patients received rdCRT after IC and were included in the primary analysis. Key eligibility: smoking history ≤20 pack-years, no active smoking, no distant metastases, molecularly confirmed HPV status. INTERVENTIONS/METHODS:Three cycles of induction TPF (docetaxel, cisplatin, 5-fluorouracil) followed by rdCRT (5600 cGy) with weekly carboplatin in clinical responders; non-responders in both QB trials and responders in the control arm of QB1 received sdCRT (7000 cGy). MAIN OUTCOMES AND MEASURES/METHODS:Primary endpoints: 3-year locoregional relapse-free survival (LRRFS) and 3-year progression-free survival (PFS). Secondary: overall survival (OS). Tertiary: disease-specific survival. RESULTS:Among 47 patients treated with rdCRT after IC, the 3-year and 5-year LRRFS were 89.3% and 86.6%. PFS was 87.2% and 84.6% at 3 and 5 years. OS was 91.5% and 89.1% at 3 and 5 years. Six patients (13%) experienced locoregional failure, and two (4%) developed distant metastases. 7/8 treatment failures (87.5%) occurred in patients with extracapsular extension. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:rdCRT following IC yields durable disease control in poor prognosis HPV-OPC, with outcomes comparable to historical benchmarks. Extended follow-up supports the safety and efficacy of this de-escalation strategy, even in patients with aggressive disease characteristics, but also underscores the need for careful patient selection, particularly in those with extracapsular extension.

PURPOSE/OBJECTIVE:Pancreatic cystic lesions (PCL) commonly undergo surveillance using MRI with MR cholangiopancreatography (MRCP). Our objective is to compare the performance of a single-shot fat-saturated T2-weighted technique with deep-learning reconstruction (DL HASTE-FS) to a conventional T2-weighted Half fourier Single-shot Turbo spin-Echo (HASTE) sequence and to MRCP for the purpose of PCL detection, characterization, and surveillance. METHODS:In this retrospective study, 91 consecutive patients underwent 3T abdominal MRI with MRCP protocol including DL HASTE-FS and conventional HASTE between 8/2/2023 and 10/3/2023. Three abdominal radiologists rated overall and lesion-specific image quality on a 5-point Likert scale, including pancreatic margin and duct sharpness, and PCL conspicuity. A subset of 70 preselected index PCLs were evaluated for cyst features, confidence of diagnosing side-branch IPMN, and suitability of DL HASTE-FS in replacing MRCP for PCL surveillance. RESULTS:DL HASTE-FS received higher scores for pancreatic duct border sharpness (4.1 vs. 3.9; p = .004), pancreatic duct visibility compared to MRCP (2.0 vs. 1.9; p = .04), cyst conspicuity (4.4 vs. 3.9; p < .001), and sharpness of cyst wall and internal septations (4.3 vs. 3.7; p < .001) compared to conventional HASTE. In contrast, conventional HASTE received higher scores for pancreatic margin sharpness (4.2 vs. 3.8; p < .001) and peripancreatic vessel clarity (4.2 vs. 3.4; p < .001). For the 70 preselected index PCLs, readers visualized more PCLs and had higher confidence in diagnosing SB-IPMN on DL HASTE-FS than on conventional HASTE (3.6 vs. 3.4; p < .001). Finally, DL HASTE-FS was deemed a suitable replacement to MRCP for more cases than conventional HASTE (83% vs. 48%; p < .001). CONCLUSION/CONCLUSIONS:DL HASTE-FS outperforms conventional HASTE for PCL detection and characterization, and is a suitable alternative to 3D MRCP in the context of PCL surveillance, potentially reducing exam time and cost.

BACKGROUND:Patients with HPV oropharyngeal cancer will live for decades with the sequelae of therapy, including radiation induced second primary cancers (SP). This study reviews and reports the incidence and outcomes of in-field SPs from the Quarterback Trials (QT) where molecular testing confirmed HPV status at diagnosis and recurrence. METHODS:Patients in the QT had <20 pack-year smoking history, locally advanced disease, and molecularly confirmed HPV status. All patients received TPF induction chemotherapy (IC). Responders were treated on protocol with reduced-dose (RD, 5600 cGy) or standard-dose (SD, 7000 cGy) chemoradiotherapy (CRT). Recurrences and SPs were confirmed by biopsy and molecular testing. RESULTS:Of the 60 eligible patients consented, 13 received SD (8 randomized to SD, 4 with inadequate response to IC, 1 withdrew consent). There were 7 HPV+ LRFs (1 SD, 6 RD) and 4 molecularly confirmed in-field non-HPV SPs (2 SD, 2 RD). All SP tumors were p53-mutated and HPV-negative. Median time to LRF and SP was 8 and 66 months, respectively. Median survival after LRF or SP was 11 months and 18+ months, respectively. CONCLUSIONS:Non-HPV SPs are not uncommon in HPV+ non-smoking patients and occurred more frequently with SD treatment, suggesting a radiation dose-dependent effect. SPs presented symptomatically. SPs are likely to become a major cause of mortality in this population over time, underscoring the need for molecular testing to guide surveillance and treatment decisions. This is especially relevant for analysis of outcomes in de-escalation trials.

BACKGROUND:Extrinsic compression of the pulmonary artery (PA) has been described with mediastinal and other thoracic masses. This compression can lead to acquired pulmonic stenosis and pulmonary hypertension. CASE SUMMARY/METHODS:A 27-year-old woman was diagnosed with Hodgkin lymphoma with a mediastinal mass compressing her PA leading to severe pulmonary hypertension, without hemodynamic compromise. She was treated with chemotherapy and had rapid resolution of the pulmonary artery compression on subsequent transthoracic echocardiogram 1 month after starting treatment. DISCUSSION/CONCLUSIONS:The current literature on the rare entity of extrinsic PA compression includes cases of surgical or percutaneous intervention to relieve compression and cases with resolution of compression based on changes in physical examination or transthoracic echocardiogram several months after initial diagnosis. This case is novel in reporting echocardiographic evidence of complete resolution of PA compression within 1 month of treatment without invasive intervention. TAKE-HOME MESSAGES/CONCLUSIONS:Pulmonary hypertension secondary to extrinsic PA compression from a mediastinal tumor is rare, but this case demonstrates that it may completely and rapidly resolve after initiation of chemotherapy. Short-interval follow-up echocardiography is helpful to reassess the degree of pulmonary hypertension after treatment.

PURPOSE/OBJECTIVE:Though prior studies have proven CTC's efficacy in outpatients, its utility in the inpatient setting has not been studied. We evaluated the efficacy of a modified CTC protocol in the inpatient setting, primarily for patients awaiting organ transplantation. METHODS:This retrospective study compared a group of inpatient CTCs from 2019 to 2021 and a randomly selected, age-matched 2:1 control group of outpatient CTCs. Both groups were assessed based on established criteria from literature. RESULTS:10 % (63/652) of CTCs were performed in the inpatient setting, of which 29 were excluded, yielding 34 inpatient cases. 90 % (589/652) of CTCs were performed in the outpatient setting, from which 68 randomly selected, age-matched patients were selected as controls. Significantly more (24 %, 8/34) inpatients expired due to extracolonic causes (vs. 1 %, 1/68 outpatients, p < 0.05). 62 % (21/34) of inpatient CTCs were reported as diagnostic (vs. 74 %, 50/68 outpatient, p = 0.22). Significantly more inpatients (12 %, 4/34) than outpatients (1 %, 1/68) were unable to tolerate two imaging positions (p = 0.02). Subsequent colonoscopy was performed in 24 % (8/34) of inpatients, revealing pathologies including colonic polyps and non-bleeding ulcers. Inpatient CTCs had lower average quality scores, significant for one reviewer (p = 0.009-0.054). Inpatients had a larger number of segments with: >25 % residual fluid (1.22-1.28 inpatients vs. 0.60-0.73 outpatients, p = 0.003-0.026) and inadequate fluid tagging (1.10 inpatients vs. 0.49 outpatients, p = 0.046-0.0501). Distention was not significantly different between groups (p = 0.317-0.410). CONCLUSION/CONCLUSIONS:Quality of inpatient CTC was inferior to outpatient CTCs across several metrics. 24 % undergoing inpatient CTC died of extracolonic causes within 22 months, and most did not have findings warranting intervention, questioning the value of this difficult exam in this patient population. Routine CT may be sufficient to exclude large or metastatic colonic lesions precluding transplant.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Accumulating evidence points to worse clinical outcomes among adults with multiple sclerosis (MS) belonging to minority or poverty-affected groups. By contrast, little is known about the outcomes of these populations with pediatric-onset MS (POMS). Individuals with POMS represent 5% of the MS population and are more racially diverse yet have been understudied regarding socioeconomic environment or characteristics. In this study, we investigated the association between childhood social determinants of health (SDOH) and brain MRI outcomes in patients with POMS. METHODS:This is a retrospective single-site cohort study of patients with POMS with brain MRI quantitatively analyzed using icobrain software to yield total white matter lesion, black hole, whole brain, white matter, and gray matter volumes. All patients with POMS evaluated at New York University Langone MS Center and who underwent high-quality volumetric MRI scans were included in this study. SDOH indicators of race, ethnicity, health insurance type, parental education, and childhood neighborhood social vulnerability index (SVI) were examined for association with MRI outcomes using linear least absolute shrinkage selection operator penalized regression modeling. Disease-modifying therapy (DMT) timing and DMT efficacy were compared for each SDOH category. RESULTS:= 0.39). There were no differences in DMT timing or efficacy between categories of social disadvantage. DISCUSSION/CONCLUSIONS:Individual-level and neighborhood-level indicators of social disadvantage are associated with worse brain MRI outcomes in POMS. Further investigation of race, ethnicity, and childhood disadvantage as risk factors of MS susceptibility and severity is needed to reduce MS health disparities.