Patterns of progression after immune checkpoint inhibitors for Hodgkin lymphoma: implications for radiation therapy.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs. We identified patients who received ICIs for HL between 2013 and 2022. Fludeoxyglucose-18 positron emission tomography (FDG-PET) before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of treatable progression included patients with ≤5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified; 69 had complete records, and of these, 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had ≤5 sites of disease (limited) on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At a median follow-up of 4.0 years, 41 of 69 patients had progressed on/after ICIs (cumulative incidence 66.4%), and of these, 22 of 41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with limited disease was 34%. The cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with limited disease before ICIs experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICIs.

Testosterone as a Biomarker for Quality of Life (QOL) Following Androgen Deprivation Therapy (ADT) and Stereotactic Body Radiotherapy (SBRT).

BACKGROUND: Androgen deprivation therapy (ADT) causes fatigue and sexual dysfunction. The time to testosterone recovery depends on patient and treatment-specific characteristics. The kinetics of testosterone recovery in men treated with neoadjuvant ADT and stereotactic body radiotherapy (SBRT) is not well established. This study seeks to characterize testosterone recovery and evaluate its relationship with the improvement in patient-reported hormonal and sexual function. METHODS: Institutional review board (IRB) approval was obtained for retrospective review of prospectively collected data. All patients with localized prostate cancer treated with short-course ADT (3-6 months of Leuprolide) and robotic SBRT (35-36.25 Gy in five fractions) at a single institution were included in this analysis. Testosterone levels were measured at the start of radiation, every 3 months for the first year, and every 6 months thereafter. Total testosterone recovery was defined as a serum level of >230 ng/dL. Sexual and hormonal function was recorded using the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of SBRT, and at each follow-up. The EPIC-26 subdomain scores were transformed to a 0-100 scale with higher scores reflecting less bother. RESULTS: Between January 2009 and May 2018, 122 men with a median age of 72 years (range: 55-89 years) received ADT followed by SBRT. Thirty-two percent (N=39) were black and 27% [N=39 were obese (BMI > 30)]. The median pre-SBRT testosterone level was 15 ng/dL (range: 3-89 ng/dL). Around 77% (N=94) of patients received 3 months of ADT. The median pre-ADT EPIC-26 Hormone and Sexual Domain Scores were 94 and 41, respectively. At 12 months, 71% (N=87) of patients recovered to a eugonadal state with a mean recovery time of 4 months post-SBRT. Hormonal and sexual subdomain scores declined significantly following ADT but recovered to within the minimally important difference (MID) for sexual and hormonal domain scores by 12 months post-SBRT. CONCLUSIONS: Testosterone recovery following short-course ADT with leuprolide and SBRT occurs rapidly in the majority of patients within one year after treatment. Quality of life domain improvements followed the testosterone recovery trend closely. Testosterone testing at follow-up appointments would allow for anticipatory counseling that may limit the bother associated with temporary quality of life decrements.

Developmental Dysplasia of the Hip: An Examination of Care Practices of Pediatricians.

OBJECTIVE: To evaluate the decision making processes of pediatricians regarding diagnosis and management of developmental dysplasia of the hip (DDH) by conducting a survey of pediatricians in the United States. STUDY DESIGN: An electronic survey was sent to multiple American Academy of Pediatrics state chapters and academic pediatrics groups, and responses were received from pediatricians in 10 states. The survey included demographics, guideline use, clinical scenarios, and referrals/imaging practices. The number of responses to each survey question and their relative frequencies were calculated. RESULTS: We received 139 responses and included 126 in our analyses. Only 50% of the responding pediatricians (63 of 126) practiced in an institution that endorses a care pathway for DDH. Only 5.6% of the pediatricians (7 of 125) have referred patients at 12-18 months between diagnosis and management to a specialist for suspected DDH, and 9.5% (12 of 125) have referred patients between 6 and 9 months. Almost one-quarter of the pediatricians (23%; 29 of 126) cited "hip click" as an abnormality that would prompt them to refer a patient to a specialist, and 72.2% (91 of 126) indicated that family history of DDH warrants an ultrasound regardless of the physical examination findings. Moreover, 10.3% of the surveyed pediatricians (13 of 126) reported being only "somewhat" or "moderately" familiar with the Barlow and Ortolani maneuvers. CONCLUSIONS: The results of this study indicate that there is an opportunity to better distribute and implement DDH guidelines. The large number of pediatrician respondents who would not refer patients to a specialist or order imaging studies appropriately represents an opportunity for education. The implementation of a care map with standard referral and imaging practices could improve the care of patients with DDH.

A case of metachronous bilateral secretory carcinoma.

Secretory carcinoma (SC) was first recognized as a distinct salivary malignancy in 2010. In the nine years since its recognition, there have been multiple reports of SC of the major and minor salivary glands, as well one case of tongue base involvement. Here we present the first reported case of bilateral SC. The first tumor, diagnosed before the recognition of SC, was classified as mucoepidermoid carcinoma. After the contralateral parotid tumor was diagnosed as SC in 2016, the two histologies were compared, and the mucoepidermoid carcinoma was reclassified as SC. In this report, we describe our patient's clinical course and review the SC literature, with a focus on pathologic diagnosis and clinical prognosis.

Developmental Dysplasia of the Hip: An Examination of Care Practices of Orthopaedic Surgeons in India.

BACKGROUND: We evaluated screening, referral and treatment practices for developmental dysplasia of the hip (DDH) in India by surveying Orthopaedic surgeons who treat patients with DDH. The survey assessed the timing of DDH presentation, resource availability, and current state of screening and diagnosis, which would help in the development of a DDH care pathway for India. METHODS: An online survey was distributed to Orthopaedic surgeons practicing in India via email and administered onsite to those attending the annual conference of the Pediatric Orthopaedic Society of India in 2019. RESULTS: 173 completed surveys were received from surgeons practicing in a predominantly urban setting. 68.8% of respondents had performed initial evaluations on children with DDH aged over 1 year in the past 12 months, and 49.1% had assessed children with DDH aged > 2 years on initial presentation. There was no consistent use of established guidelines, with only 30% of respondents stating that a care pathway was in place at their institution. However, 91.9% would support the implementation of a care pathway developed in India, to decrease the incidence of delayed diagnosis and facilitate earlier intervention. 85% of respondents had ready access to ultrasound scans and 95.4% had access to X-rays. CONCLUSIONS: In India, there is still a large number of late-presenting cases of DDH, which could be improved with effective screening. The development of a care pathway for DDH in India is well-supported by Orthopaedic surgeons and may help decrease the incidence of late presenting cases; potentially improving outcomes, decreasing morbidity, and upskilling local practitioners.

Developmental Dysplasia of the Hip: An Examination of Care Practices of Pediatric Orthopaedic Surgeons in North America.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common condition, affecting 1% to 2% of full-term infants. The American Academy of Orthopaedic Surgeons (AAOS) and American Academy of Pediatrics have published guidelines detailing best practices for DDH screening and treatment. The purpose of this survey was to determine DDH treatment practices of pediatric orthopaedic surgeons in North America. METHODS: We queried orthopaedic surgeon members of the Pediatric Orthopaedic Society of North America (POSNA) about referral patterns, treatment practices, and use of DDH guidelines. The survey included demographics, clinical scenarios, referrals patterns, and ultrasound practices. RESULTS: Of the 1392 members of POSNA, we received 432 total responses and included 353 in statistical analyses. Results show that 68% (233/342) of surgeons practice in an institution that does not endorse a standard care pathway for DDH. Of surgeons who personally use a DDH care pathway, the AAOS guidelines were most cited (143/353, 41%). The majority (94%, 316/337) of surgeons do not believe that universal ultrasound screening should be adopted in the United States. Responses regarding ultrasound screening for "high risk" infants as outlined by AAOS varied based on risk factor. Many (57%, 200/353) surgeons have performed initial evaluations for patients over 12 months of age. While 80% (260/327) of orthopaedic surgeons believe that primary care providers are referring patients appropriately, only 57% (183/323) believe that primary care providers are ordering imaging studies appropriately. CONCLUSIONS: Results from this survey of POSNA membership indicate an opportunity to better distribute and implement DDH guidelines. In addition, the implementation of a care map with a focus on standard referral and imaging practices could improve the care of patients with DDH by: (1) reducing the total cost of care, (2) increasing the use of appropriate imaging, (3) increasing timely referral for DDH care, and (4) reducing the presentation rate of walking age DDH patients. LEVEL OF EVIDENCE: The level of evidence rating for this survey-based study is level IV.

Patellar-Trochlear Morphology in Pediatric Patients From 2 to 11 Years of Age: A Descriptive Analysis Based on Computed Tomography Scanning.

BACKGROUND: Despite the critical role the trochlea plays in patellofemoral (PF) pathology, the development of the trochlea is poorly understood. The purpose of this study was 2-fold: (1) Describe quantitative osseous and soft tissue anatomy of the patella and trochlea in skeletally immature cadaveric specimens utilizing known measurements used in PF instability, and (2) evaluate additional measurement techniques in the sagittal plane as they relate to PF morphologic development. METHODS: Thirty-one skeletally immature fresh frozen cadaveric knees between the ages of 2 and 11 years old were evaluated using 0.625 mm computed tomography scans. In the axial plane, measurements included condylar height asymmetry, trochlear facet asymmetry, trochlear depth, osseous sulcus angle, cartilaginous sulcus angle, patella sulcus angle, and tibial tubercle-trochlear groove distance. In the sagittal plane, measurements included previously undescribed measurements of trochlear length and condylar height asymmetry which are based on the anterior femoral cortex. RESULTS: Analysis of trochlear morphology using condylar height asymmetry (both axial and sagittal), trochlear facet asymmetry, and trochlear depth and length demonstrated an increase in the size of the medial and lateral trochlea as age increased. There was more variability in the change of size of the medial trochlea (height, length, and facet length) than the lateral trochlea. The osseous sulcus angle, cartilaginous sulcus angle, and patella sulcus angle decreased (became deeper) with age until after 8 years and then plateaued. CONCLUSIONS: This cadaveric analysis demonstrated that there is an increase in the medial and lateral trochlear height as age increased by all measurements analyzed. The findings also demonstrate that the shape of the patella and trochlea change concurrently, which suggests that there may be interplay between the 2 during development. These new sagittal measurement techniques evaluating the medial, central, and lateral trochlear height and length with respect to age may help guide clinicians when investigating patellar instability in skeletally immature patients. LEVELS OF EVIDENCE: Level IV.

Squamous Cell Papilloma in a Student Aviator.

BACKGROUND: Although oropharyngeal squamous cell papilloma (OSCP) is not uncommon in the general population, reports of OSCP in aviators are rare. This case report serves as a call for flight surgeons to consider all oropharyngeal pathology as a potential source of airway compromise during flight, and highlights regional risk factors for developing malignancies of the oropharynx.CASE REPORT: A 24-yr-old male foreign national student aviator from a central Asian country was at Fort Rucker for flight training. He presented to the clinic with a chief complaint of sore throat and cough for 2 d. He was afebrile but reported a history of a "throat" mass which was previously evaluated by a U.S. military otolaryngologist. Said mass was approximately 0.5 cm × 0.5 cm, irregular appearing, inflamed, and protruding from the inferior aspect of the right tonsil. Previous biopsy report revealed a squamous cell papilloma and, after consideration of the pilot's training program, active surveillance of the lesion was mutually agreed upon until the student's training had concluded and definitive excision was performed.DISCUSSION: A robust history and physical exam including an occupational, social, and environmental exposure history is crucial to diagnosis. Foreign national patients often have unique backgrounds that merit consideration when developing a differential diagnosis, assessment, and plan. In the field of Flight Medicine, a patient's occupational demands are essential to his or her care. In particular, any potential obstruction of the airway during flight must be considered, even if a pathology does not represent an immediate threat to the pilot's health.Swinson K, Burlile J, Pavelites J. Squamous cell papilloma in a student aviator. Aerosp Med Hum Perform. 2019; 90(11):978-981.

Quadriceps Tendon Graft Anatomy in the Skeletally Immature Patient.

BACKGROUND: The quadriceps tendon (QT) is increasingly considered for primary and revision anterior cruciate ligament reconstruction in skeletally immature patients, as it may be harvested as a purely soft tissue graft with considerable tissue volume. Because of distinct rectus tendon (RT) separation from the QT complex, the potential for RT retraction exists and could lead to QT weakness after QT graft harvest. PURPOSE: To describe the anatomy of the pediatric QT and clarify decussation of the RT and QT to avoid the risk of delayed RT retraction and QT weakness after QT graft harvest. STUDY DESIGN: Descriptive epidemiology study. METHODS: Nine cadaveric knee specimens (aged 4-11 years) underwent gross dissection. Coronal-plane width and depth of the QT were measured at intervals proximal to the superior pole of the patella at distances of 0.0, 0.5, 1.0, and 1.5 times the length of the patella. The distance was measured from the superior patellar pole to the point of RT separation from the remainder of the deeper/posterior QT. RESULTS: The median patellar length was 28 mm (interquartile range, 26-37 mm). The coronal-plane width of the QT was larger superficially/anteriorly when closest to the patella but wider when measured deeper/posteriorly as the tendon extended proximally. The median distance between the superior pole of the patella and RT separation from the QT was 0.95 times the patellar length. The distance to widening of the deeper/posterior aspect of the QT was 1.14 times the patellar length proximal to the patella. CONCLUSION: The RT begins a distinct separation from the QT above the superior pole of the patella at a median of 0.95 times the patellar length in skeletally immature specimens. The deeper/posterior aspect of the QT begins to increase in coronal-plane width proximally after a distance of 1.14 times the patellar length above the knee, while the superficial/anterior aspect of the tendon continues to narrow. Awareness of the separation of the RT from the QT, and the coronal-plane width variation aspects of the QT proximally, is important for surgeons utilizing the QT as a graft to avoid inadvertent release of the RT from the rest of the QT complex.