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.

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.

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.

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.

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.

Meniscectomy in children: a long-term follow-up study.

In order to more accurately document the effects of meniscus removal, 20 children and adolescents with isolated meniscal tears were examined an average of 5.5 years after surgery. All patients with concomitant ligamentous injuries and a history of prior surgery on either knee, and those with bilateral knee pathology or knee pathology outside the meniscus, were excluded. At followup, 60% of the 20 study patients had unsatisfactory results. The clinical results did not correlate with the site of meniscectomy, the type of meniscal tear, the severity of radiographic changes, or whether the patient had total or partial meniscectomy. Evaluation of lower extremity muscle function revealed a statistically significant (P less than 0.05) decrease in hip abductor strength in patients with unsatisfactory results. This study indicates that meniscectomy in the child or adolescent is not a benign procedure, and that failure to rehabilitate hip abductor strength to normal levels significantly comprises the clinical end results.

Family study of spondylolysis and spondylolisthesis.

Seventy index patients and 222 first-degree relatives with spondylolysis or spondylolisthesis have been studied by means of interview and clinical and radiological examinations. The index patients had an average age of 18 years, and included 43 females and 27 males. Following Wiltse's classification, 18 patients had dysplastic lesions and 52 had isthmic defects. The first-degree relatives included 99 parents and 125 siblings and children of the index patients. Both isthmic and dysplastic defects occurred in most families, regardless of the classification of the index patient. Isthmic defects were consistently more frequent than dysplastic defects. Spina bifida occulta occurred at the lumbosacral area in 61% of the index patients; in the first-degree relatives, spina bifida occulta was most common among the siblings and children of index patients, and occurred more often in relatives of index patients with dysplastic lesions than in those with isthmic lesions.

Cervical spondylolisthesis associated with the multiple nevoid basal cell carcinoma syndrome.

Cervical spondylolisthesis is a rate vertebral anomaly that has not been associated with other major congenital abnormalities. In a 16-year-old girl, lower cervical spondylolisthesis was associated with a multiple nevoid basal cell carcinoma syndrome. The salient features of cervical spondylolisthesis include occipital headache, nuchal rigidity, torticollis, painful range of limited motion, hypesthesia, and depressed deep tendon reflexes. The treatment in the patient was anterior vertebral body fusion. Awareness of this associated problem and prompt treatment are essential for prevention of neurologic loss.