Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes.

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

Real-world outcomes according to treatment strategies in ALK-rearranged non-small-cell lung cancer (NSCLC) patients: an Italian retrospective study.

PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received. PATIENTS: We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions. RESULTS: After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9-11.2] and 11.1 months [CI 95% 9.2-13.8], respectively, while TTF were 10.2 [CI 95% 8.5-12.6] and 11.9 months [CI 95% 9.7-17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8-54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0-73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6-NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3-34.0)] (P < 0.0001). CONCLUSION: The sequential administration of crizotinib and a new generation ALKis provided a remarkable clinical benefit in this real-life population, being an interesting option to consider in selected patients.

Radiologic evaluation of juvenile tillaux fractures of the distal tibia.

This study evaluated the accuracy of plain radiographs and computerized tomography (CT) in assessing juvenile Tillaux fractures of the distal tibia. A simulated Tillaux fracture was made in four cadaver specimens and displaced 0, 1, 2, 3, and 5 mm. Plain radiographs and CT were performed on each specimen at each amount of displacement, and the results were compared with the actual amount of displacement present. Plain radiographs and CT were accurate within 1 mm in depicting the actual fracture displacement about 50% of the time. CT was more sensitive than plain radiographs in detecting fractures with >2 mm of displacement. Fracture displacement of >2 mm is generally considered an indication for fracture reduction. Because of its sensitivity in detecting fractures displaced >2 mm, CT is the preferred imaging modality in the assessment of juvenile Tillaux fractures.

Development dysplasia of the hip from birth to six months.

The term "developmental dysplasia or dislocation of the hip" (DDH) refers to the complete spectrum of abnormalities involving the growing hip, with varied expression from dysplasia to subluxation to dislocation of the hip joint. Unlike the term "congenital dysplasia or dislocation of the hip," DDH is not restricted to congenital problems but also includes developmental problems of the hip. It is important to diagnose these conditions early to improve the results of treat- ment, decrease the risk of complications, and favorably alter the natural history. Careful history taking and physical examination in conjunction with advances in imaging techniques, such as ultrasonography, have increased the ability to diagnose and manage DDH. Use of the Pavlik harness has become the mainstay of initial treatment for the infant who has not yet begun to stand. If stable reduction cannot be obtained after 2 weeks of treatment with the Pavlik harness, alternative treatment, such as examination of the hip under general anesthesia with possible closed reduction, is indicated. If concentric reduction of the hip cannot be obtained, surgical reduction of the dislocated hip is the next step. Toward the end of the first year of life, the toddlerTs ability to stand and bear weight on the lower extremities, as well as the progressive adaptations and soft- tissue contractures associated with the dislocated hip, preclude use of the Pavlik harness.

Cervical spine disorders in children.

Care of children with disorders of the cervical spine requires an understanding of the anatomic and biologic features particular to the developing pediatric spine. Congenital and developmental alterations further complicate evaluation and treatment of children. Basic knowledge of pediatric cervical spine disorders in Down syndrome, Klippel-Feil syndrome, osteochondrodysplasias, mucopolysaccharidoses, and post-traumatic instability is essential for all orthopedic surgeons. Thorough patient evaluation and appropriate early management may prevent potentially serious neurologic injury and other complications related to cervical spine pathology.

Treatment of posttraumatic cubitus varus in the pediatric population with humeral osteotomy and external fixation.

Cubitus varus may occur after supracondylar humerus fractures. Poor fixation, however, complicates operative treatment of cubitus varus. We discuss the use of external fixation in the treatment of cubitus varus. Five patients had humeral osteotomies with external fixation. The preoperative humeroulnar angle (HUA) averaged -24.2 degrees. The immediate postoperative HUA averaged 12 degrees, and the final angle averaged 13 degrees. Duration of external fixation averaged 8.9 weeks. Complications were one transient radial neurapraxia, one superficial pin infection, and one keloid. No loss of correction or motion occurred with external fixation; we recommend external fixation as safe and effective.

Tarsal coalition: depiction and characterization with CT and MR imaging.

PURPOSE: To compare computed tomography (CT) and magnetic resonance (MR) imaging in the detection, localization, and characterization of tarsal coalitions. MATERIALS AND METHODS: Preoperative CT and MR images were obtained for 10 feet in nine patients (eight male and one female patients), aged 11-18 years who were unresponsive to conservative therapy. Results from two blinded readers were compared with results from surgery. RESULTS: Five calcaneonavicular and four medial subtalar coalitions were found at surgery. One patient had synovitis. CT depicted six coalitions and four were characterized correctly, but the fibrous coalitions were not characterized correctly. MR depicted all coalitions and seven were characterized correctly, including the fibrous coalitions. At MR imaging, proliferative synovitis was incorrectly characterized as a fibrous coalition. CONCLUSION: These results suggest that MR imaging depicts all coalitions but may not be able to help differentiate synovitis from fibrous coalitions and that CT has limitations in the depiction of fibrous coalitions.

Risk factors in Klippel-Feil syndrome.

STUDY DESIGN: This study kinematically evaluated radiographs of the cervical spine of patients with the Klippel-Feil syndrome in flexion and in extension to determine alterations from normal motion and potential risk. OBJECTIVES: The results in the study group were compared with those of a control group and with published standards for expected motion of the cervical spine. SUMMARY OF BACKGROUND DATA: The body of orthopedic and neurologic literature suggests a significant problem with neurologic deficit in patients with Klippel-Feil syndrome. No previous study has evaluated the kinematics of the cervical spine with a control group of normal individuals and published standards. METHOD: Lateral flexion-extension radiographs of the cervical spine of 111 patients with Klippel-Feil syndrome were kinematically evaluated to determine the motion of each open interspace and to compare motion with that of a control group and published standards. RESULTS: A statistically significant difference of increased motion per open interspaces in the upper cervical segment was noted in individuals with Klippel-Feil syndrome when compared with the control population. Conversely, total motion of the lower cervical segment was significantly decreased in the Klippel-Feil population when compared with normal controls. Lower segment motion per open interspace was not significantly different when the two groups were compared. CONCLUSION: The results of this study suggest that individuals with Klippel-Feil syndrome with hypermobility of the upper cervical segment are at risk for neurologic sequelae, whereas those with alteration in motion of the lower cervical segment are predisposed to degenerative disease.

Spinal considerations in the young athlete.

The young athlete involved in modern sports activity may be subject to considerable problems involving the spine. An appreciation of the differences in spinal anatomy, development, and kinematics facilitates the evaluation of each individual. While a variety of factors are operant that could contribute to difficulty in evaluation and treatment, an organized approach with an emphasis on naturally-occurring variations of the immature spine will allow for appropriate recommendations. While concern exists regarding the individual with congenital, developmental, or hereditary conditions, it is important to respect the individuality of these young athletes and to assess each problem in a comprehensive manner before recommending full or restricted activity. Current research should yield important information that will serve as more absolute guidelines in formulating recommendations for involved adolescent athletes and will establish the natural history of conditions that today remain obscure.

Sequelae and reconstruction after septic arthritis of the hip in infants.

We evaluated the residual deformity and late treatment of thirty-four hips of thirty-one children who had had septic arthritis when they were less than one year old. The hips were classified into four groups on the basis of radiographic changes. Type-I deformity (five hips) involved transient ischemia of the epiphysis, with or without mild coxa magna, and these hips did not need reconstruction. Type-II deformity (eleven hips) included deformity of the epiphysis, physis, and metaphysis, and these hips needed an operation to prevent subluxation; the goals of the operation included improvement in acetabular coverage, improvement in abductor efficiency by epiphyseodesis or transfer of the greater trochanter, and equalization of limb-length discrepancy by epiphyseodesis of the contralateral limb. Type-III deformity (five hips) involved malalignment of the femoral neck, with extreme anteversion or retroversion or with a pseudarthrosis of the femoral neck that necessitated a realignment osteotomy of the proximal part of the femur or bone-grafting of the pseudarthrosis. Type-IV deformity (thirteen hips) included destruction of the femoral head and neck, with persistence of only a remnant of the medial base of the femoral neck. In the hips that had a Type-IV deformity, the complex clinical problems, which included severe limb-length discrepancy and incompetent articulation of the hip, necessitated operations such as Pemberton osteotomy, trochanteric arthroplasty, arthrodesis, epiphyseodesis of the contralateral limb, and lengthening of the ipsilateral tibia. The functional result was satisfactory in all five hips that had a Type-I deformity, in seven of eleven that had a Type-II deformity, in three of four that had a Type-III deformity, and in only four of thirteen that had a Type-IV deformity.

Nonoperative treatment for painful adolescent spondylolysis or spondylolisthesis.

Eighty-two adolescent patients with symptomatic spondylolysis or spondylolisthesis were treated by nonoperative modalities. Patients' ages ranged from 6.5 to 21 years, and follow-up ranged from 1 to 14.3 years. Thirty-one patients became asymptomatic, 17 had significant but incomplete relief of pain, nine had no relief, and 25 required surgical treatment for pain. Of 12 patients with grade 3 or 4 slip, only one had significant relief of pain, whereas 48 of 70 patients with lesser degrees of slip had significant relief of pain. Nonoperative treatment of degrees of spondylolisthesis of less than or equal to grade 2 can reliably relieve pain in two-thirds of patients.

Atlantoaxial instability in mucopolysaccharidosis type VII.

We report a 15-year-old boy with mucopolysaccharidosis (MPS) Type VII (Sly disease) who was found to have atlantoaxial instability with quadriparesis. Subluxation of C1 on C2 has also been documented in patients with Type I and Type IV MPS. Routine screening of the cervical spine is recommended in patients with "MPS Type VII" so that delayed diagnosis of instability, which may lead to neurologic compromise, is avoided.

Use of bone scintigraphy in the management of slipped capital femoral epiphysis.

Fourteen patients with slipped capital femoral epiphysis (SCFE) who had high-resolution and magnification bone scintigraphy during treatment were studied. By demonstrating the vascular status of the femoral head and physiologic condition of the growth plate, scintigraphy was found to assist the clinician in the management of patients with this disorder.

Occipito-atlantal instability in children. A report of five cases and review of the literature.

We are reporting the cases of five patients who had occipito-atlantal instability, a rare condition that may be due to either trauma or congenital abnormalities. In three of the patients the instability was secondary to trauma. The clinical and neurological manifestations were varied and included cardiorespiratory arrest, motor weakness, quadriplegia, torticollis, pain in the neck, vertigo, and projectile vomiting. All of the patients underwent posterior arthrodesis of the occiput to the first or second cervical vertebra. In the patients who had trauma-related instability, surgery was performed when immobilization in a cast failed to stabilize the spine; in the patients who had a congenital abnormality, arthrodesis was indicated because of persistent symptoms and the potential for catastrophe with minor trauma. Based on our experience, we recommend surgical stabilization by posterior arthrodesis when this form of instability of the cervical spine is diagnosed.

Bilateral fracture of the pedicle of the second cervical vertebra in the young child.

We report the cases of five children, six to eighteen months old, who had bilateral fracture of the pedicles of the second cervical vertebra. The children were treated with gentle cervical traction in mild extension or were maintained in near-anatomical reduction in a Minerva jacket or halo cast. The fractures united in four patients. One patient underwent fusion to stabilize the spine.