Patel, Shreyaskumar

11008 Background: SARC028 is the first multicenter Phase II study of P monotherapy in patients (pts) with STS and BS. Designed to detect clinical efficacy signals in multiple histologies, the study collected blood & tissue samples on all pts. We report extended clinical follow-up and in-depth biomarker correlates of response. Methods: The primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints were safety, 12 wk progression-free survival (PFS), and overall survival (OS). The STS arm had 10 pts in each of 4 cohorts: undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), synovial sarcoma (SS) and leiomyosarcoma (LMS). The BS arm included 40 pts with osteosarcoma (OS), Ewing sarcoma (ES) or dedifferentiated chondrosarcoma (CS). Pre- and on-P biopsies were required as well as blood at multiple time points. Tumor was assessed for PD-L1 expression (clone 22C3) and immune infiltrates by multi-color IHC (Vectra). Ongoing analyses include circulating cytokine and checkpoint levels and exome (DNA), transcriptome (RNA), and T-cell receptor (TCR) sequencing. Results: 86 pts were enrolled, 80 were evaluable for response. For STS, median follow-up was 14.5 months. The ORR in the overall STS cohort was 18% and the 12-wk PFS 55% [95% CI, 42-71]). Clinical activity was variable by histologic subtype with 40% ORR in UPS (1 CR and 3PR out of 10 evaluable pts), 2 PR/10 were seen in DDLPS, 1PR/10 in SS and 0/10 in LMS. For BS, median follow-up was 12.3 months (ORR 5%; 12-wk PFS 28% [95% CI, 14-41]), with 1PR/22 OS, 1PR/5 CS and 0/13 ES. 70 pre-P tissues were analyzed (11 excluded for insufficiency), with PD-L1+ in 3/70 (4%); all 3 were UPS. Of the 2 evaluable pts, 1 had CR and 1 PR. 2 OS were PD-L1+ on multi-color IHC, 1 had PR. All PD-L1+ samples had CD8+ T-cell infiltration. There were no post-P PD-L1+ samples. Conclusions: P has clinical activity in UPS and LPS, and expansion cohorts in those subtypes are planned. Pre-treatment PD-L1 expression was infrequent, but correlated with T-cell infiltration and response in UPS & OS. Ongoing biomarker analyses that may guide combination strategies are ongoing and will be presented at the meeting. Clinical trial information: NCT02301039.

Study Design: Systematic review. Objective: Surgical decompression and reconstruction of symptomatic spinal metastases has improved the quality of life in cancer patients. However, most data has been collected on cohorts of patients with mixed tumor histopathology. We systematically reviewed the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine. Methods: A systemic review of the literature was conducted to answer the following questions: Question 1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine. Question 2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and hormonal naivety favor operative intervention. Question 3. Establish whether clinical outcomes vary with the evolution of operative techniques. Results: A total of 16 studies met the preset inclusion criteria. All included studies were retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone-naivety on overall survival. Additionally, studies consistently demonstrated an improvement in motor function and the ability to maintain/regain ambulation following surgery resulting in moderate strength of recommendation. All other parameters were of insufficient or low strength. Conclusions: There is a dearth of literature regarding the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. Based on existing evidence, it appears that the surgical treatment of prostate metastases to the spine has consistently favorable results. While no consistent preoperative indicators favor nonoperative treatment, hormone-naivety and high Karnofsky performance scores have positive effects on survival and clinical outcomes.

OBJECTIVEPrimary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved.METHODSA systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis.RESULTSA total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06).CONCLUSIONSWhile the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of osteosarcoma. A limitation of this systematic review is that lesions amenable to subsequent resection or tumors inherently more sensitive to adjuvants would exaggerate a therapeutic effect of these interventions when studied in a retrospective fashion.

Study Design Review of the literature. Objective Surgery and cement augmentation procedures are effective palliative treatment of symptomatic spinal metastases. Our objective is to systematically review the literature to describe the survival, prognostic factors, and clinical outcomes of surgery and cement augmentation procedures for breast cancer metastases to the spine. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results The median postoperative survival for metastatic breast cancer was 21.7 months (8.2 to 36 months), the mean rate of any pain improvement was 92.9% (76 to 100%), the mean rate of neurologic improvement was 63.8% (53 to 100%), the mean rate of neurologic decline was 4.1% (0 to 8%), and the local tumor control rate was 92.6% (89 to 100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included hormonal (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2) receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, surgery consistently yielded neurologic improvements in patients presenting with a deficit with a minimal risk of worsening; however, negative prognostic factors associated with shorter survival following surgery include estrogen receptor/progesterone receptor negativity, HER2 negativity, and a short DFI.

Introduction Treatment of symptomatic spinal metastases through surgical decompression and reconstruction is known to improve quality of life in patients with cancer. However, most studies have been performed on patients with mixed tumor histopathology. We systematically review the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine to determine the indications and outcomes of the surgical treatment. Material and Methods A systemic review of the literature was conducted to answer the following questions: Q1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine; Q2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and favorable hormonal naivety for operative intervention; Q3. Establish whether clinical outcomes vary with the evolution of operative techniques. Expert consensus was obtained using a modified Delphi process. Results A total of 16 studies met the preset inclusion criteria. These studies were all retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone naivety on overall survival. In addition, studies consistently demonstrated an improvement in motor function and the ability to maintain/regain ambulation following surgery resulting in moderate strength of recommendation. All other parameters were of insufficient or low strength. Conclusion There is scant literature on the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. On the basis of the existing evidence, it appears that the surgical treatment of prostate metastases to the spine has consistently favorable results. While no consistent preoperative indicators favor nonoperative treatment, hormone naivety and high Karnofsky Performance Scores have positive effects on survival and clinical outcomes.

Introduction Surgical treatment and cement augmentation procedures are effective palliative techniques for the treatment of symptomatic spinal metastases. However, clinical results specific to a breast cancer cohort are generally lacking. We aim to systematically review the literature for clinical outcomes following operative interventions and prognostic factors for the treatment of breast metastases to the spine. Specifically, we describe the survival and clinical outcomes of surgery and cement augmentation procedures for breast metastases to the spine and to determine prognostic variables that may help recognize which patients will perform better or worse following surgery. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results A total of 19 surgical studies, 4 cement augmentation studies, and 6 nonsurgical prognostic variable studies met the preset inclusion criteria. All but three studies (two surgical and one cement augmentation) were retrospective in nature, and all studies were of level of evidence IV. Median postoperative survival for metastatic breast cancer was 21.7 months (8.2–36 months), mean rate of pain improvement was 92.9% (76–100%), mean rate of neurological improvement was 63.8% (53–100%), mean rate neurological decline was 4.1% (0–8%), and mean rate LTC was 92.6% (89–100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included: hormonal (estrogen and progesterone) and HER2 receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, studies consistently found that surgery resulted in neurological improvement for a majority of patients, with a minimal risk of worsening, and kyphoplasty studies reported a high rate of pain control. Increased postoperative survival 2002 onwards was likely due to FDA approval of new chemotherapies. However, specific factors associated with shorter survival following surgery involve hormone and HER2 receptor status and disease-free interval.

Purpose The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome. Patients and Methods There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis. Results RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model–adjusted P < .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival. Conclusion Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS.