Current Immunotherapies for Sarcoma: Clinical Trials and Rationale.

Sarcoma tumors are rare and heterogeneous, yet they possess many characteristics that may facilitate immunotherapeutic responses. Both active strategies including vaccines and passive strategies involving cellular adoptive immunotherapy have been applied clinically. Results of these clinical trials indicate a distinct benefit for select patients. The recent breakthrough of immunologic checkpoint inhibition is being rapidly introduced to a variety of tumor types including sarcoma. It is anticipated that these emerging immunotherapies will exhibit clinical efficacy for a variety of sarcomas. The increasing ability to tailor immunologic therapies to sarcoma patients will undoubtedly generate further enthusiasm and clinical research for this treatment modality.

Atypical presentation of fever as hypersensitivity reaction to oxaliplatin.

Oxaliplatin, a third-generation, platinum-based agent is widely used, most commonly in the FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) regimen, which is the first-line therapy in metastatic colorectal adenocarcinoma and adjuvant chemotherapy in stage III colorectal cancer. Platinum-based products are well known for causing hypersensitivity reactions. Fever associated with oxaliplatin-hypersensitivity reactions typically follows a specific pattern. It usually starts during the oxaliplatin infusion or immediately after (within hours instead of days) and happens after several administrations (mean 2-25) with unpredictable clinical presentations. We report a case of oxaliplatin-induced hypersensitivity reaction manifesting as fever but with unusual presentation than the aforementioned features.

Exceptional Clinical Response to BRAF-Targeted Therapy in a Patient with Metastatic Sarcoma.

Soft tissue sarcomas (STS) are a rare and heterogeneous group of tumors arising from mesenchymal tissue comprising 1% of all adult cancers. The prognosis of metastatic STS is dismal. As there are few active drugs, there is a critical need to find new therapeutic alternatives in order to improve outcomes. Most sarcoma subtypes are fairly resistant to standard chemotherapy regimens and/or have a short duration of response. The era of molecular targeted therapy may present new treatment options for metastatic STS and an opportunity to drive biomarker discovery and personalized medicine. This case report describes a patient with a synchronous metastatic high-grade sarcoma who was treated with BRAF-targeted therapy with resolution of his metastatic lesions. To our knowledge, this exceptional response has not been described in sarcoma literature. The patient presented with a large anterior abdominopelvic wall mass. Biopsy showed a high-grade spindle cell sarcoma. Staging scans confirmed two pulmonary metastases. He was initiated on combination chemotherapy with mixed results. He received 50 Gy of radiation to the primary tumor followed by two additional cycles of combination chemotherapy, with an interval increase in the size of the pulmonary metastases.  Molecular testing revealed a BRAF V600E mutation in the primary tumor. The patient was initiated on dabrafenib/trametinib with a dramatic response and resolution of his pulmonary metastases. The patient underwent surgical resection of his primary mass, and pathology confirmed no evidence of residual disease.  Detailed genetic characterization of STS coupled with novel therapeutic strategies, including molecular targeted therapy, may have the potential to transform the care of patients diagnosed with sarcoma.

Hair repigmentation associated with the use of lenalidomide: graying may not be an irreversible process!

We report the first case of progressive hair repigmentation associated with the use of lenalidomide in an elderly patient with multiple myeloma. The influence of lenalidomide on follicular melanogenesis may involve removing the inhibitory influences of some cytokines such as IL-1, IL-6 and TNF-α. In addition, certain endocrine effects of lenalidomide on the hypophyseal-adrenal axis could explain its action on hair pigmentation. We further hypothesize that lenalidomide may be capable of stimulating migration and/or differentiation of melanocytes to promote repigmentation of gray hair follicles. Pending the clarification of how hair repigmentation occurs with lenalidomide, our observation materializes the concept that hair graying may not be an irreversible process, which opens avenues for targeted therapeutics in the fields of cosmetics and anti-aging medicine.

Wrong-sided and wrong-level neurosurgery: a national survey.

OBJECT: Perhaps the single greatest error that a surgeon hopes to avoid is operating at the wrong site. In this report, the authors describe the incidence and possible determinants of incorrect-site surgery (ICSS) among neurosurgeons. METHODS: The authors asked neurosurgeons to complete an anonymous survey. These surgeons were asked to report the number of craniotomies and lumbar and cervical discectomies performed during the previous year, as well as whether ICSS had occurred. They were also asked detailed questions regarding the potential determinants of ICSS. RESULTS: There was a 75% response rate and a 68% survey completion rate. Participating neurosurgeons performed 4695 lumbar and 2649 cervical discectomies, as well as 10,203 craniotomies. Based on this self-reporting, the incidence of wrong-level lumbar surgery was estimated to be 12.8 [corrected] occurrences per 10,000 operations. The ICSSs per 10,000 cervical discectomies and craniotomies were 7.6 [corrected] and 2.0, [corrected] respectively. Neurosurgeons recognized fatigue, unusual time pressure, and emergent operations as factors contributing to ICSS. For spine surgery, in particular, unusual patient anatomy and a failure to verify the operative site by radiography were also commonly reported contributors. CONCLUSIONS: Neurosurgical ICSSs do occur, but are rare events. Although there are significant limitations to the survey-based methodology, the data suggest that the prevention of such errors will require neurosurgeons to recognize risk factors and increase the use of intraoperative imaging.

Effects of a cervical disc prosthesis on segmental and cervical spine alignment.

OBJECT: Cervical arthroplasty offers the promise of maintaining motion of the functional spinal unit (FSU) after anterior cervical discectomy. The impact of cervical arthroplasty on sagittal alignment of the FSU needs to be addressed, together with its effect on overall sagittal balance of the cervical spine. METHODS: The authors prospectively reviewed radiographic and clinical outcomes in 14 patients who received the Bryan Cervical Disc prosthesis (Medtronic Sofamor Danek, Memphis, TN), for whom early (< 6 months) and late (6-24 months) follow-up data were available. Static and dynamic radiographs were measured by hand and computer to determine the angles formed by the endplates of the natural disc preoperatively, those formed by the shells of the implanted prosthesis, the angle of the FSU, and the C2-7 Cobb angle. The range of motion (ROM) was also determined radiographically, whereas clinical outcomes were assessed using the Neck Disability Index (NDI), and Short Form-36 (SF-36) questionnaires. The ROM was preserved following surgery, with a mean preoperative sagittal rotation angle of 8.96 degrees , which was not significantly different from the late postoperative value of 8.25 degrees . When compared with the preoperative disc space angle, the shell endplate angle in the neutral position became kyphotic in the early and late postoperative periods (mean change -3.8 degrees in the late follow-up period; p = 0.0035). The FSU angles also became significantly more kyphotic postoperatively, with a mean change of -6 degrees (p = 0.0006). The Cobb angles varied widely preoperatively and did not change significantly after surgery. There was no statistical correlation between the NDI and SF-36 outcomes and cervical kyphosis. CONCLUSIONS: Cervical arthroplasty preserves motion of the FSU. Both the endplate angle of the treated disc space and the angle of the FSU became kyphotic after insertion of the Bryan prosthesis. The overall sagittal balance of the cervical spine, however, was preserved.

Early clinical and biomechanical results following cervical arthroplasty.

OBJECT: Spinal arthroplasty may become the next gold standard for the treatment of degenerative cervical spine disease. This new modality must be studied rigorously to ensure in vivo efficacy and safety. The authors review the preliminary clinical experience and radiographic outcomes following insertion of the Bryan Cervical Disc Prosthesis (Medtronic Sofamor Danek, Memphis, TN). METHODS: This prospective cohort study included 26 patients undergoing single- or two-level implantation of the Bryan artificial cervical disc for treatment of cervical degenerative disc disease resulting in radiculopathy and/or myelopathy. Radiographic and clinical assessments were made preoperatively 1.5, 3 months, and at 6, 12, and up to 24 months postoperatively. The Neck Disability Index (NDI) and Short Form-36 (SF-36) questionnaires were used to assess pain and functional outcomes. Segmental sagittal rotation from C2-3 to C6-7 was measured using quantitative motion analysis software. A total of 30 Bryan discs were placed in 26 patients. A single-level procedure was performed in 22 patients and a two-level procedure in the other four. Follow-up duration ranged from 1.5 to 27 months, with a mean duration of 12.3 months. A statistically significant improvement in the mean NDI scores was seen between pre- and late postoperative follow-up evaluations. A trend toward improvement in the SF-36 physical component was also found. Motion was preserved in the treated spinal segments (mean range of motion 7.8 degrees ) for up to 24 months postsurgery. The relative contribution of each segment to overall spinal sagittal rotation differed depending on whether the disc was placed at C5-6 or C6-7. Overall cervical motion (C2-7) was moderately increased on late follow-up evaluations. CONCLUSIONS: The Bryan artificial cervical disc provided in vivo functional spinal motion at the treated level. Overall cervical spinal motion was not significantly altered. Sagittal rotation did not change significantly at any level after surgery.