Faculty Bibliography

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.

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/UNASSIGNED:The purpose of this study was to compare the demographic differences of the most common peripheral nerve compressions in the upper extremity-carpal tunnel syndrome (CTS), ulnar nerve compression (UNC) at the elbow, combined CTS and UNC, radial tunnel syndrome (RTS), and posterior interosseous nerve syndrome (PINS)-as a means to better understand the etiologies of each. METHODS/UNASSIGNED:< .05). RESULTS/UNASSIGNED:< .001). CONCLUSIONS/UNASSIGNED:The demographics of patients with various compressive neuropathies were not homogeneous, suggesting different etiologies.

PURPOSE/OBJECTIVE:The extensor retinaculum of the wrist, a thickening of the deep forearm fascia, is often used as do- nor graft material for annular pulley reconstructions and bone-retinaculum-bone grafts for ligament reconstructions. The purpose of our study was to identify the relationships between the radial and ulnar styloids, readily recogniz- able topographic landmarks of the wrist, and the anatomic boundaries of the retinaculum. METHODS:The extensor retinacula of 12 preserved, right cadaver wrists (3 male and 9 female) were studied by gross dissection using 3.5-power loupe magnification. The proxi- mal and distal extents of the retinaculum were identified and marked with needles, and their distances from the radial and ulnar styloids measured to determine the lengths of the retinaculum on both sides. RESULTS:The extensor retinaculum on the radial side extended 23.9 ± 2.9 mm proximal to the radial styloid and 5.8 ± 2.6 mm distal to the styloid for a total length of 29.7 ± 3.8 mm. On the ulnar side, the retinaculum extended 2.4 ± 1.4 mm proximal to the ulnar styloid and 17.9 ± 2.6 mm distal to the styloid for a total length of 20.3 ± 2.9 mm. CONCLUSIONS:The extensor retinaculum has a consis- tent relationship with the readily recognized topographic landmarks of the radial and ulnar styloids. The use of the extensor retinaculum as donor material for pulley and liga- ment reconstruction make these findings useful for surgical planning.

PURPOSE/OBJECTIVE:This article presents the outcomes of repairs of flexor tendon lacerations within digital sheaths performed more than 2 weeks after injury. METHODS:A retrospective review of 46 patients; 37 with finger lacerations involving a total of 54 severed tendons in 42 fingers and nine with thumb lacerations of the flexor pollicis longus (FPL). In those patients with finger lacera- tions, 30 lacerations were isolated to the flexor digitorum profundus (FDP; 17 in Zone I and 13 in Zone II), and 12 involved both FDP and flexor digitorum superficialis (FDS) for a total of 24 tendon lacerations. RESULTS:The delay in surgery for finger lacerations ranged from 2 to 96 weeks (average: 8.5 weeks) and for thumb lacerations, 2 to 17 weeks (average: 5.5 weeks). In Zone I finger lacerations, postoperative flexion of the distal interphalangeal (DIP) joint averaged 35° with 82% of patients regaining total active motion (TAM) in the good to excellent range. In Zone II injuries isolated to the FDP tendon, postoperative DIP joint flexion averaged 36.5° with 73% of patients regaining good to excellent TAM. In Zone II injuries involving both flexor tendons, final average DIP flexion was 37° with only 45% of patients regaining good to excellent TAM. All patients with FPL lacerations regained at least 30° (average: 46°) of active interphalangeal joint flexion. CONCLUSION/CONCLUSIONS:When certain conditions exist that are deter- mined at surgery, delayed repairs of isolated FDP lacera- tions in fingers and FPL lacerations in thumbs can restore satisfactory mobility. Results are less favorable when both flexor tendons in the finger are lacerated and only the FDP repaired.

The objective of this study was to determine the role of ad- junctive surgical procedures on the median nerve for carpal tunnel syndrome as measured by somatosensory evoked potentials (SEPs) on the nerve. Fifty-five median nerves in 47 patients were studied. In each patient, a base-line SEP was recorded in the operating room prior to incision and then intraoperatively following each of three sequential pro- cedures: division of the transverse carpal ligament, an epi- neurolysis of the nerve, and finally, either an epineurotomy or epineurectomy that we refer to as a "limited internal neu- rolysis" since it did not involve any intraneural dissection of fascicles. Comparison of the baseline mean SEP latency for the median nerve, referred to as N19 (negative polarity = 19 msec), showed a statistically significant improvement following each of the three procedures. The average reduc- tion of latency after ligament release alone was 1.52 msec, and the total improvement in latency from baseline through limited internal neurolysis was 4.72 msec. Our study showed that epineurolysis followed by a limited internal neurolysis using either an epineurotomy or epineurectomy produced a significant electrophysiologic improvement in the median nerve. There was no significant difference when comparing epineurotomy and epineurectomy.

Background PVSRIPO, a novel intratumoral viral immunotherapy, infects cells via CD155, which is widely expressed on solid tumors and antigen-presenting cells (APC). Infection is lethal in malignant cells, but a unique, activating, nonlethal infection of local APCs yields type-I/III interferon (IFN)-dominant inflammation with subsequent anti-tumor T-cell priming and activation resulting in anti-tumor efficacy. In preclinical models, PVSRIPO-dependent inflammation upregulated the PD-1/L1 pathway, and greater anti-tumor response was observed with PVSRIPO + anti-PD-1/L1 (aPD-1/L1). Promising clinical activity with PVSRIPO monotherapy was observed in patients with recurrent glioblastoma and advanced aPD-1- refractory melanoma.1 2 Collectively, these results warrant further clinical investigation of PVSRIPO +/- aPD-1/L1. Methods LUMINOS-103 (NCT04690699) is a phase (Ph) 1/2, open-label, multi-center, single-arm basket trial evaluating repeat administration of PVSRIPO +/- aPD-1/L1 in adults with solid tumors. Trial objectives are to assess the safety and tolerability of PVSRIPO monotherapy in each cohort in Ph 1 and the safety, tolerability, and antitumor efficacy of PVSRIPO + aPD-1/L1 in each cohort in Ph 2. The first two study cohorts include patients with muscle-invasive bladder cancer being treated in the neoadjuvant setting (A) and patients with metastatic bladder cancer being treated in the 1st/2nd line setting (B); these cohorts have been described previously.3 Cohort C includes patients with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) being treated in the neoadjuvant setting; Cohort D includes patients with recurrent/ metastatic HNSCC with a PD-L1 Combined Positive Score >=1 being treated in the 1st line setting. Eligibility: HNSCC patients must have histologically or cytologically-proven SCC of the oral cavity, oropharynx, hypopharynx, or larynx. All patients must have prior and boosted PV immunization and tumors amenable to injection and biopsy. Key exclusion criteria: Requirement for oxygen supplementation, systemic or intratumoral therapy <=6 months prior to the first dose of study drug, CNS metastases requiring immediate treatment, systemic immunosuppressive medications <=4 weeks prior to the first dose of study drug, and severe active comorbidities. Patients who are HIV+, HBV+ or HCV+ are eligible provided they meet certain criteria. Primary endpoints include safety (all cohorts), tolerability (all cohorts), surgical complication rate (A, C), pathologic treatment effect/response (A, C), and objective response rate (B, D). Secondary endpoints include overall survival (all cohorts), pathologic downstaging and relapse-free survival (A, C), duration of response and progression- free survival (B, D), and assessment of tumor/blood biomarkers (all cohorts)

Proximal interphalangeal (PIP) joint fracture dislocations are challenging injuries to treat. Multiple and varied treatments have been proposed. We present the use of cerclage wiring as a helpful technique in these challenging scenarios. The technique has the benefit of securing fracture fragments from the volar or dorsal base of middle phalanges or a comminuted fracture involving the entire articular surface. We report on the use of cerclage wires in eight patients (average: 43 years of age). Three patients had volar base fractures, three dorsal base fractures, and two impacted fractures involving the entire articular surface. All fractures healed, and average postoperative PIP active flexion motion arc was 21° to 95° (functional arc of 74°). We believe cerclage wire fixation is an effective and reproducible method to treat intra-articular fractures of middle phalanges, especially comminuted fractures involving the entire articular surface, and should be available to hand surgeons treating these difficult injuries.