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Objective To determine the prognostic significance of histologic type/subtype in a large series of patients with primary resected retroperitoneal sarcoma. Summary Background Data The histologic diversity and rarity of retroperitoneal sarcoma has hampered the ability to predict patient outcome. Methods From a single-institution, prospective database, 675 patients treated surgically for primary, non-metastatic retroperitoneal sarcoma during 1982–2010 were identified and histologic type/subtype was reviewed. Clinicopathologic variables were analyzed for association with disease-specific death (DSD), local recurrence (LR), and distant recurrence (DR). Results Median follow-up for survivors was 7.5 years. The predominant histologies were well-differentiated liposarcoma, dedifferentiated liposarcoma, and leiomyosarcoma. Five-year cumulative incidence of DSD was 31%, and factors independently associated with DSD were R2 resection, resection of ≥3 contiguous organs, and histologic type. Five-year cumulative incidence for LR was 39% and for DR was 24%. R1 resection, age, tumor size, and histologic type were independently associated with LR; size, resection of ≥3 organs, and histologic type were independently associated with DR. Liposarcoma and leiomyosarcoma were associated with late recurrence and DSD (as long as 15 years from diagnosis). For solitary fibrous tumor, local recurrence was uncommon (<10%), but early distant recurrence was common (36% at 5 years). Nomograms were developed to predict DSD, LR, and DR. Conclusions Histologic type/subtype is the most important independent predictor of DSD, LR, and DR in primary retroperitoneal sarcoma. Histology predicts the pattern and incidence of LR and DR and will aid in more accurate patient counseling and selection of patients for adjuvant therapy trials.

Treatment with the CDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.

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Objective To construct a postoperative nomogram to estimate the risk of local recurrence for patients with desmoid tumors. Background The standard management of desmoid tumors is resection, but many recur locally. Other options include observation or novel chemotherapeutics, but little guidance exists on selecting treatment. Methods Patients undergoing resection during 1982-2011 for primary or locally recurrent desmoids were identified from a single-institution prospective database. Cox regression analysis was used to assess risk factors and to create a recurrence nomogram, which was validated using an international, multi-institutional dataset. Results Desmoids were treated surgically in 495 patients (median follow-up 60 months). Of 439 patients undergoing complete gross resection, 100 (23%) had recurrence. Five-year local recurrence–free survival (LRFS) was 69%. Eight patients died of disease, all after R2 resection. Adjuvant radiation was not associated with improved LRFS. In multivariate analysis, factors associated with recurrence were extremity location, young age, and large tumor size, but not margin. Abdominal wall tumors had the best outcome (5-year LRFS 91%). Age, site, and size were used to construct a nomogram with concordance index 0.703 in internal validation and 0.659 in external validation. Integration of additional variables (R1 margin, gender, depth, and primary vs. recurrent presentation) did not importantly improve concordance (internal concordance index 0.707). Conclusions A postoperative nomogram including only size, site, and age predicts local recurrence and can aid in counseling patients. Systemic therapies may be appropriate for young patients with large, extremity desmoids, but surgery alone is curative for most abdominal wall lesions.

Purpose of Review-Liposarcoma, a rare disease, is classified into five histologic subtypes. These include well-differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS), both characterized by chromosome 12q13-15 amplification. This review will focus on the clinical management of WDLS and DDLS and examine recent molecular studies that have the potential to affect clinical management.Recent findings-Outcome of patients with WDLS and DDLS depends on completeness of surgical resection as well as tumor location and histologic subtype. Risk of recurrence is high for patients with dedifferentiated histology or retroperitoneal location. We now understand that surgical outcomes are poor for patients with rapidly growing or incompletely resectable tumors, so these patients should be managed non-operatively. Radiation and chemotherapy have low response rates in WDLS and DDLS, but novel agents targeted at chromosome 12 gene products MDM2 and CDK4 have shown promise in pre-clinical studies and are being tested in clinical trials. Cell line, tissue microarray, and genomic analyses have identified additional targets including ZIC1, TOP2A, AURKA, and IGF-1R, which could form the basis of future therapies.Summary-Although complete surgical resection is currently the most effective treatment for WDLS and DDLS, the majority of patients with retroperitoneal liposarcoma will eventually have recurrence and die of disease. It is hoped that a multi-modality approach, which incorporates targeted therapies and complete surgical resection, will significantly improve patient outcomes.

Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P < 0.001) in the NLR low/TMB high group compared to the NLR high/TMB low group. NLR is a suitable candidate for a cost-effective and widely accessible biomarker, and can be combined with TMB for additional predictive capacity.

Importance Over 90% of well-differentiated/de-differentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective CDK4/CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and xenografts. Our prior phase 2 study demonstrated that treatment with palbociclib (200mg daily × 14d every 21d) resulted in clinical benefit in WD/DDLS but moderate hematologic toxicity. It is important to understand whether palbociclib at a new dose and schedule, 125mg daily × 21d every 28d, results in clinical benefit and manageable toxicity. Objective To determine the progression-free survival (PFS) at 12 weeks of patients with WD/DDLS treated with palbociclib. Design Phase 2, non-randomized, open label clinical trial. Patients enrolled from December 2011 to January 2014 and followed to March 2015. Setting Memorial Sloan Kettering Cancer Center Participants 60 patients with advanced WD/DDLS, age ≥ 18 years, and measurable disease by RECIST 1.1 Interventions: Patients received oral palbociclib at 125mg daily for 21 days in 28-day cycles. Main outcomes and measures Primary endpoint was PFS. Secondary endpoints included response rate and toxicity. Results 30 patients were enrolled in the initial cohort and 30 more in an expansion cohort. Median age was 61.5 (range 35–87); 52% were male; median ECOG score was 0 (range 0–1). PFS at 12 weeks was 57.2% (2-sided 95% CI: 42.4% – 68.8%). The median PFS was 17.9 weeks (2-sided 95% CI: 11.9 – 24.0 weeks). There was 1 complete response. Toxicity was primarily hematologic and included neutropenia (grade 3: 33%, grade 4: 3%) but no neutropenic fever. Conclusions and relevance In patients with advanced WD/DDLS, treatment with palbociclib was associated with a favorable PFS and occasional tumor response. This dose and schedule appears active and may have less toxicity than 200mg × 14d.