Health-related quality of life in patients with metastatic basal cell carcinoma treated with cemiplimab: Analysis of a phase 2 trial.

BACKGROUND: A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health-related quality of life (QoL) for this patient population is reported. METHODS: Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales. RESULTS: Patients reported low symptom burden and moderate-to-high functioning at baseline. Maintenance for QLQ-C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex-16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%-88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales. CONCLUSIONS: The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden.

Increasing Pitch Count is Associated with Increasing Elbow Flexion Angle at Ball Release in Youth Baseball Pitchers.

BACKGROUND: Baseball is one of the most popular sports among youth athletes in the United States, and among these players, pitchers are at a particularly high risk of sustaining an injury. Overuse of the arm from repetitive pitching is a common mechanism for injury. Despite the attention that overuse injury has received, little is known regarding the mechanism that leads to elbow injury. This study aims to determine the effect of increasing pitch count on elbow flexion at ball release in a youth pitching cohort. The authors hypothesize that elbow flexion will increase as pitch count increases. METHODS: Study subjects included volunteers from youth baseball players from local teams and public advertisements. Retro-reflective markers attached to bony landmarks were placed on the players according to ISG recommendations. Pitchers threw an indoor simulated game. Three-dimensional marker trajectories were collected using a 12-camera optical motion capture system, and ball velocity was captured using a radar gun. Voluntary maximal isometric strength of the internal and external rotators was evaluated before and after pitching. Paired two-tailed t-tests were performed to determine if a significant change occurred between the fresh and fatigued sets. RESULTS: Twelve adolescent male pitchers were recruited. Eleven of 12 pitchers completed the prescribed 6 sets of 15 pitches, culminating in a 90-pitch simulated game. The ball speed in the second set was found to be the highest in all pitchers and was considered the "peak set" (p = .021) while ball speed was the slowest in the sixth set of pitches and was therefore considered the "fatigue set" (p = .001). There was a moderate but statistically significant inverse correlation between elbow flexion at ball release and maximum internal rotation velocity (p = .005). Elbow flexion at ball release was also significantly positively correlated with shoulder abduction at ball release (p = 0.004). Elbow flexion at ball release was not significantly correlated with ball velocity (p=.108). DISCUSSION: In a simulated game laboratory setting, increasing pitch count was associated with increasing elbow flexion angle at ball release in youth baseball pitchers. These findings demonstrate that pitching with fatigue may cause biomechanical changes that have been associated with increased rates of elbow injury in the adult throwing population. Further investigation on the association between elbow flexion angle and elbow injury in the youth baseball population is needed.

Quality of life in cemiplimab-treated patients with locally advanced basal cell carcinoma in a Phase II clinical trial.

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC).Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles.Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue.Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue.Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.

Locally advanced basal cell carcinoma (laBCC) is a type of skin cancer that has the potential to invade surrounding tissues including bone, cartilage, nerve and muscle. Cemiplimab-rwlc is approved in the US for patients with laBCC following a therapy called hedgehog inhibitor (HHI) treatment or for whom HHIs are not appropriate. In a Phase II clinical trial, intravenous (in the vein) cemiplimab 350 mg every 3 weeks for up to nine treatment cycles resulted in clinically meaningful antitumor activity in patients with laBCC who progressed on or were intolerant to HHIs.This analysis evaluated health-related quality of life, symptom burden, emotions and functional status in these patients using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires. Baseline scores (scores at the start of the clinical trial) showed moderate to high levels of functioning and low symptom burden that, except for fatigue, were maintained or improved over the course of cemiplimab treatment. These results show that despite the presence of fatigue, health-related quality of life and functional status were maintained with cemiplimab across the study duration.

Real-World Treatment Patterns and Outcomes of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma Treated in US Oncology Practices.

Background: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US. Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018-2021). A clinical trial-like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan-Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort. Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6-9.0) months and 16.4 (13.3-21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8-29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age <60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status <3-4 (HR range, 0.13-0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without. Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.

Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma.

PURPOSE: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma. METHODS: Patients with advanced melanoma were eligible for enrollment into four cohorts: three for patients without and one for patients with previous anti-PD-1 therapy in the advanced disease setting. Patients were treated with fianlimab 1,600 mg and cemiplimab 350 mg intravenously once every 3 weeks for up to 51 weeks, with an optional additional 51 weeks if clinically indicated. The primary end point was objective response rate (ORR) per RECIST 1.1 criteria. RESULTS: ORRs were 63% for patients with anti-PD-1-naïve melanoma (cohort-6; n = 40; median follow-up 20.8 months), 63% for patients with systemic treatment-naïve melanoma (cohort-15; n = 40; 11.5 months), and 56% for patients with previous neo/adjuvant treatment melanoma (cohort-16; n = 18, 9.7 months). At a median follow-up of 12.6 months for the combined cohorts (6 + 15 + 16), the ORR was 61.2% and the median progression-free survival (mPFS) 13.3 months (95% CI, 7.5 to not estimated [NE]). In patients (n = 13) with previous anti-PD-1 adjuvant therapy, ORR was 61.5% and mPFS 12 months (95% CI, 1.4 to NE). ORR in patients with previous anti-PD-1 therapy for advanced disease (n = 15) was 13.3% and mPFS 1.5 months (95% CI, 1.3 to 7.7). Treatment-emergent and treatment-related adverse events ≥grade 3 (G3) were observed in 44% and 22% of patients, respectively. Except for increased incidence of adrenal insufficiency (12%-G1-4, 4%-G3-4), no new safety signals were recorded. CONCLUSION: The current results show a promising benefit-risk profile of fianlimab/cemiplimab combination for patients with advanced melanoma, including those with previous anti-PD-1 therapy in the adjuvant, but not advanced, setting.

Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease.

BACKGROUND: Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis. METHODS: An Intratumoral Immunotherapy Clinical Trials Expert Panel composed of international key stakeholders from academia and industry was assembled. A multiple choice/free response survey was distributed to the panel, and the results of this survey were discussed during a half-day consensus meeting. Key discussion points are summarized in the following manuscript. RESULTS: The panel determined unique clinical trial designs tailored to different stages of cancer development-from premalignant to unresectable/metastatic-that can maximize the chance of capturing the effect of intratumoral immunotherapies. Design elements discussed included study type, patient stratification and exclusion criteria, indications of randomization, study arm determination, endpoints, biological sample collection, and response assessment with biomarkers and imaging. Populations to prioritize for the study of intratumoral immunotherapy, including stage, type of cancer and line of treatment, were also discussed along with common barriers to the development of these local treatments. CONCLUSIONS: The SITC Intratumoral Immunotherapy Clinical Trials Expert Panel has identified key considerations for the design and implementation of studies that have the greatest potential to capture the effect of intratumorally delivered immunotherapies. With more effective and standardized trial designs, the potential of intratumoral immunotherapy can be realized and lead to regulatory approvals that will extend the benefit of these local treatments to the patients who need them the most.

Evaluation of Differences in Patellar Height After Patellar Stabilization Procedures Not Intended to Address Patella Alta: A Multicenter Study.

Background: Recent studies have reported conflicting results as to whether isolated medial patellofemoral ligament reconstruction (MPFLr) leads to decreased patellar height. Purpose: To investigate if patellar stabilization surgery not intended to address patella alta influences patellar height. Study Design: Cohort study; Level of evidence, 3. Methods: A multicenter retrospective chart review was conducted, and patients who underwent MPFLr, medializing tibial tuberosity osteotomy (TTO), and/or trochleoplasty between 2016 and 2020 were included. The Caton-Deschamps index (CDI) was calculated from radiographs obtained preoperatively, 2 weeks postoperatively, and 3 months postoperatively. The preoperative CDI value was compared with the 2-week postoperative and 3-month postoperative values according to stabilization procedure (isolated MPFLr, isolated TTO, MPFLr + TTO, MPFLr + trochleoplasty, and MPFLr + trochleoplasty + TTO) using the paired t test. Analyses of the 1-bundle versus 2-bundle MPFLr technique and the presence of lateral retinacular release or lateral retinacular lengthening were conducted on the isolated MPFLr and combined MPFLr + TTO cohorts. Results: A total of 356 knees were included. Statistically significant pre- to postoperative decreases in CDI were seen in all stabilization procedures analyzed (P≤ .017 for all). Within the isolated MPFLr cohort, this significant decrease was seen at 2 weeks postoperatively with the 2-bundle technique (ΔCDI = -0.09; P < .001) but not with the 1-bundle technique (ΔCDI = -0.01; P = .621). Conclusion: The different surgical techniques analyzed in the current study affected patellar height, even when a distalizing TTO was not performed. The decrease was dependent on surgical technique, with a 2-bundle MPFLr leading to a statistically significant decrease and a 1-bundle MPFLr effecting no change.

High response rate with extended dosing of cemiplimab in advanced cutaneous squamous cell carcinoma.

BACKGROUND: Cemiplimab (Libtayo®), a human monoclonal immunoglobulin G4 antibody to the programmed cell death-1 receptor, is approved for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC), who are not candidates for curative surgery or curative radiation, using an every-3-weeks (Q3W) dosing interval. Pharmacokinetic modeling indicated that Ctrough of extended intravenous dosing of 600 mg every 4 weeks (Q4W) would be comparable to the approved intravenous dosage of 350 mg Q3W. We examined the efficacy, pharmacokinetics, and safety of cemiplimab dosed Q4W. METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review. RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n=14) achieving complete response and 40% (n=25) achieving partial response. The most common treatment-emergent adverse events were diarrhea, pruritus, and fatigue. CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit-risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen.

Biomechanical Characteristics of Ulnar Collateral Ligament Injuries Treated With and Without Augmentation: A Network Meta-analysis of Controlled Laboratory Studies.

BACKGROUND: Treatment of ulnar collateral ligament (UCL) tears with suture tape augmentation has gained interest given preliminary reports of favorable biomechanical characteristics. No study to date has quantitatively assessed the biomechanical effects of multiple augmentation techniques relative to the native UCL. PURPOSE: To perform a systematic review and meta-analysis of controlled laboratory studies to assess and comparatively rank biomechanical effects of UCL repair or reconstruction with or without augmentation. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: PubMed, OVID/Medline, and Cochrane databases were queried in January 2023. A frequentist network meta-analytic approach was used to perform mixed-treatment comparisons of UCL repair and reconstruction techniques with and without augmentation, with the native UCL as the reference condition. Pooled treatment estimates were quantified under the random-effects assumption. Competing treatments were ranked in the network meta-analysis by using point estimates and standard errors to calculate P scores (greater P score indicates superiority of treatment for given outcome). RESULTS: Ten studies involving 206 elbow specimens in which a distal UCL tear was simulated were included. UCL reconstruction with suture tape augmentation (AugRecon) restored load to failure to a statistically noninferior magnitude (mean difference [MD], -1.99 N·m; 95% CI, -10.2 to 6.2 N·m; P = .63) compared with the native UCL. UCL reconstruction (Recon) (MD, -12.7 N·m; P < .001) and UCL repair with suture tape augmentation (AugRepair) (MD, -14.8 N·m; P < .001) were both statistically inferior to the native UCL. The AugRecon condition conferred greater load to failure compared with Recon (P < .001) and AugRepair (P = .002) conditions. AugRecon conferred greater torsional stiffness relative to all other conditions and was not statistically different from the native UCL (MD, 0.32 N·m/deg; 95% CI, -0.30 to 0.95 N·m/deg; P = .31). Medial ulnohumeral gapping was not statistically different for the AugRepair (MD, 0.30 mm; 95% CI, -1.22 to 1.82 mm; P = .70), AugRecon (MD, 0.57 mm; 95% CI, -0.70 to 1.84 mm; P = .38), or Recon (MD, 1.02 mm; 95% CI, -0.02 to 2.05 mm; P = .055) conditions compared with the native UCL. P-score analysis indicated that AugRecon was the most effective treatment for increasing ultimate load to failure and torsional stiffness, whereas AugRepair was the most effective for minimizing medial gapping. CONCLUSION: AugRecon restored load to failure and torsional stiffness most similar to the parameters of the native UCL, whereas Recon and AugRepair did not restore the same advantageous properties at time zero. Medial ulnohumeral gapping during a valgus load was minimized by all 3 treatments. Based on network interactions, AugRecon was the superior treatment approach for restoring important biomechanical features of the UCL at time zero that are jeopardized during a complete distal tear.

Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study.

BACKGROUND: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. METHODS: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing. FINDINGS: Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Rice-Body Synovitis, Foreign Body Reaction, and Rotator Cuff Failure After Subacromial Balloon Spacer Augmentation of a Rotator Cuff Repair: A Case Report.

CASE: A 66-year-old woman presented with shoulder pain and weakness 4 months after augmentation of a rotator cuff repair with a Stryker InSpace subacromial balloon spacer. A magnetic resonance imaging (MRI) demonstrated a failed rotator cuff repair, large effusion with rice bodies, synovitis, axillary lymphadenopathy, loose anchors, and erosive changes to the greater tuberosity. Arthroscopy revealed balloon fragmentation surrounded by diffusely hyperemic synovium without repairable cuff tissue. Final cultures proved negative for infection. Histologic evaluation revealed ulcerated synovium with diffuse chronic and focal acute inflammation. CONCLUSION: Despite promising early results, augmentation of a rotator cuff repair with a subacromial balloon spacer introduces a risk of inflammatory reaction that may mimic a deep infection and compromise rotator cuff healing.

Evaluation, Treatment, and Outcomes of Batter's Shoulder.

PURPOSE OF REVIEW: This article reviews the incidence of batter's shoulder, the relevant biomechanics that predispose the lead shoulder to a posterior instability event, the evaluation and workup of posterior labral injury, the surgical technique for arthroscopic posterior labral repair, the postoperative rehabilitation process, and the clinical outcomes and return to sport after treatment of batter's shoulder. RECENT FINDINGS: New epidemiological studies have demonstrated the relatively low incidence of batter's shoulder at the professional baseball level with 85% of the injured players successfully returning to the sport with nonoperative management. However, recent studies have reinforced the limited historical literature that players requiring surgery are able to return to their prior sport at a high level. Batter's shoulder is a subtype of posterior glenohumeral instability caused by the significant forces experienced by the lead shoulder during the baseball swing. Although an uncommon injury, batter's shoulder is a source of significant time away from competition. In patients who do not improve with nonoperative management, arthroscopic posterior labral repair can reliably return players to sport. Future research studies should consider opportunities for injury prevention.

Cancer cell-derived type I interferons instruct tumor monocyte polarization.

Monocytes are highly plastic immune cells that modulate antitumor immunity. Therefore, identifying factors that regulate tumor monocyte functions is critical for developing effective immunotherapies. Here, we determine that endogenous cancer cell-derived type I interferons (IFNs) control monocyte functional polarization. Guided by single-cell transcriptomic profiling of human and mouse tumors, we devise a strategy to distinguish and separate immunostimulatory from immunosuppressive tumor monocytes by surface CD88 and Sca-1 expression. Leveraging this approach, we show that cGAS-STING-regulated cancer cell-derived IFNs polarize immunostimulatory monocytes associated with anti-PD-1 immunotherapy response in mice. We also demonstrate that immunosuppressive monocytes convert into immunostimulatory monocytes upon cancer cell-intrinsic cGAS-STING activation. Consistently, we find that human cancer cells can produce type I IFNs that polarize monocytes, and our immunostimulatory monocyte gene signature is enriched in patient tumors that respond to anti-PD-1 immunotherapy. Our work exposes a role for cancer cell-derived IFNs in licensing monocyte functions that influence immunotherapy outcomes.

New Opportunities in Assessing Return to Performance in the Elite Athlete: Unifying Sports Medicine, Data Analytics, and Sports Science.

Sports medicine literature has historically reported return to sport rates, but recent interest has shifted to return to previous performance. However, the measurement and understanding of performance in the elite athlete population has continued to evolve. Recent advancements in sport analytics, wearable technology, and player-tracking systems have improved our understanding of performance in the elite athlete. Sports medicine researchers should collaborate with sports science teams to continue investigating the validity and reliability of emerging technology, assist in interpretation of big data, and remain accountable to the goals of our athletic population. Future studies in sports medicine should consider using these detailed, granular assessments to address the demands of the elite athlete population.

Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer.

BACKGROUND: In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. METHODS: Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1-16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. RESULTS: Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77-13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08-12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. CONCLUSIONS: Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.

Change in humeral anchor position significantly affects isometry in ulnar collateral ligament repair: a 3-dimensional computer modeling study.

BACKGROUND: Medial ulnar collateral ligament (UCL) repair utilization is increasing in recent years, bolstered by shorter rehabilitation and satisfactory clinical outcomes. Although previous literature has illustrated the importance of tunnel position on restoring graft isometry in reconstruction, there remains a paucity of literature guiding anchor placement in UCL repair. The purpose of this study is to design a 3-dimensional (3D) elbow model to understand the effect of anchor location on UCL repair isometry. METHODS: A 3D computer model of an elbow joint was created using computed tomographic and magnetic resonance imaging MRI scans from a single patient. The humeral and ulnar attachments of the UCL were plotted using 3 methodologies: (1) geometric cloud mapping and (2) quantitative measurements from the anatomic studies by Camp et al and (3) Frangiamore et al. A 3.5-mm-diameter clockface was placed on each attachment site, which allowed for simulation of 12 distinct 1.75-mm deviations in anchor position. The 3 models were ranged through 0°-120° at 10° increments, and the 3D distances were measured between the ligament centroids. The humeral and ulnar anchors were sequentially repositioned around the clockfaces, and construct lengths were again measured to evaluate changes in isometry. A paired Student t test was performed to determine if there was a significant difference in isometry between the humeral and ulnar anchor deviations. RESULTS: Using method 1, the UCL repair length at 90° of elbow flexion was 26.8 mm. This construct underwent 13.6 mm of total excursion for a 46.4% change in length throughout its arc of motion. Method 2 produced a 19.3-mm construct that underwent 0.8 mm of excursion for a 3.9% length change throughout the arc. Method 3 produced a 24.5-mm construct that underwent 2.3 mm of excursion for a 9.4% length change. Identifying ligament footprints using the quantitative anatomic measurements from Camp et al and Frangiamore et al improved construct isometry through 120° of flexion (length changes of 3.9% and 9.4%, respectively) when compared to using the geometric cloud technique alone (46.4% length change). Humeral anchor deviations produced a significant increase in repair construct excursion compared with ulnar anchor deviations (P < .001). CONCLUSION: When performing UCL repair, small deviations in humeral anchor position may significantly influence ligament repair isometry. Using quantitative anatomic data may help identify anchor positions with improved repair isometry. Particularly when addressing detachments of the humeral footprint, surgeons should be critical of the humeral anchor position in order to restore native anatomy and optimal biomechanics.

Hedgehog pathway inhibitor real-world treatment patterns in patients with basal cell carcinoma: a claims-based analysis.

Aims: To examine real-world treatment patterns for Hedgehog pathway inhibitors (HHIs) for the treatment of advanced basal cell carcinoma. Patients & methods: HHI initiators between January 2013 and June 2019 were identified from IBM MarketScan® claims data. Time to treatment discontinuation and reinitiation were estimated using Kaplan-Meier methods using a 60-day grace period. Results: Among 526 patients with basal cell carcinoma who initiated an HHI, median time to first discontinuation was 144 days, and risk of discontinuation by 12 months was 88.0%. Probability of reinitiation within 12 months was 19.7%, and median time to second discontinuation was 118 days. Conclusion: HHI discontinuation was common and reinitiation uncommon in clinical practice. Future research should evaluate persistence with recently approved therapies.

This study examined patterns of discontinuation and reinitiation of Hedgehog pathway inhibitors (HHIs) such as vismodegib or sonidegib for patients with basal cell carcinoma, the most common form of skin cancer. Initiation of HHI treatment was identified from prescriptions filled by patients with commercial insurance or Medicare who had basal cell carcinoma. Discontinuation was defined as a gap of more than 60 days without treatment, after drug supply had run out. Among the 526 patients identified, one-half had discontinued HHI treatment within about 5 months and 88% had discontinued treatment within 1 year. Fewer than 20% of patients restarted treatment. Discontinuations are common but restarting treatment is uncommon among patients with basal cell carcinoma treated with HHIs.