OBJECTIVE:To determine the prognostic significance of histologic type/subtype in a large series of patients with primary resected retroperitoneal sarcoma.
BACKGROUND: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, nonmetastatic retroperitoneal sarcoma during 1982 to 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 or more 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 or more 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, LR 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.
Background.
Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, ...however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared.
Materials and Methods.
We conducted a single‐center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases.
Results.
Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow‐up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006–2010 and 2011–2013 had better overall survival than patients diagnosed in 2000–2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes.
Conclusion.
Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma.
Implications for Practice:
Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy.
The overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary metastatic melanoma has not been directly compared. A retrospective analysis of 3,454 patients with melanoma and distant metastases was conducted. Patients with mucosal melanoma had inferior overall survival. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting.
Background
Resection of hepatocellular carcinoma (HCC) offers a chance of cure, but recurrence is common and survival is often limited. The clinical and pathological characteristics of long-term ...survivors have not been well studied.
Methods
We retrospectively reviewed 212 patients who underwent partial hepatectomy for HCC with curative intent from 1992 to 2006. Fifty patients who survived beyond 10 years were compared with 109 patients who died of recurrence within 10 years.
Results
Multivariate analysis showed that tumors <5 cm (odds ratio OR 2.3,
p
= 0.04), solitary tumors (OR 3.2,
p
= 0.01), and absence of vascular invasion (OR 2.3,
p
= 0.04) were independently associated with actual 10-year survival. However, more than 20% of long-term survivors also possessed established poor prognostic factors, including α-fetoprotein >1000 ng/mL, unfavorable serum inflammatory indices, tumor size >10 cm, microvascular invasion, poor tumor differentiation, cirrhosis, and metabolic syndrome. None of the 10-year survivors had an R1 resection. While 77% of the short-term survivors developed recurrence within 2 years, 42% of the 10-year survivors developed recurrence during their decade of follow-up, although most of the recurrences among 10-year survivors were intrahepatic and amenable to further treatment. Among patients who survived beyond 10 years, 42% remained alive without recurrence.
Conclusions
In this largest Western series of actual 10-year survivors after HCC resection, almost one in four patients survived over a decade, even though nearly half of this subset had developed recurrence. While many well-known variables were associated with a poor outcome, only a positive microscopic margin precluded long-term survival.
Purpose
While previously thought to be clinically indolent, recent data suggest significant late metastatic capacity of solitary fibrous tumors (SFTs). We define prognostic factors for recurrence and ...disease-specific death (DSD) in resected primary SFTs.
Methods
Resected primary SFTs from 1982 to 2015 were identified from a prospective, single institutional database. Risk factors for local (LR) and distant recurrence (DR), and DSD were assessed using competing risk analysis.
Results
A total of 219 patients with median follow-up of 6.1 (0.1–22) years were included. Five- and 10-year cumulative DSD was 9 and 11%, respectively. Size greater than the median 8 cm, gender, location, and complete gross resection were significantly associated with DSD (
p
< 0.05). Five- and 10-year cumulative risk (CR) of LR was 4 and 7%, whereas 5- and 10-year CR of DR was 13 and 16%, respectively. LR was associated with location (
p
= 0.02) and tumor size (
p
= 0.02), and DR was associated with size (
p
< 0.01). Histopathologic classification did not predict long-term behavior with both malignant and benign tumors demonstrating capacity for DR and associated death. Tumors in the thoracic cavity and abdomen/retroperitoneum presented the greatest risk of DR (16 and 27% 10-year CR). On multivariate analysis, size ≥ 8 cm (hazard ratio 2.89,
p
= 0.05) and tumor location in chest or abdominal/retroperitoneal cavity (hazard ratio 2.68,
p
= 0.01) significantly impacted DSD.
Conclusions
Recurrence is highly associated with DSD and events occur as late as 16 years after initial presentation, including in patients with initially considered benign tumors. Patients with large (≥ 8 cm) tumors in the chest or abdominal/retroperitoneal cavity are at greatest risk.
Background
The prognosis of signet ring cell (SRC) gastric adenocarcinoma is regarded as poor, although studies addressing outcomes in relation to non-SRC tumors are conflicting. Our objective was to ...compare the survival of SRC tumors with stage-matched intestinal-type tumors in a cohort of Western patients.
Methods
Review of a prospectively maintained database identified 569 patients undergoing curative resection (R0) from 1990 to 2009. Patients were divided into three histologic groups on the basis of the Lauren classification: SRC (
n
= 210), intestinal well- or moderately differentiated (WMD,
n
= 242) disease, and intestinal poorly differentiated (PD,
n
= 117) disease. Patient demographics, clinicopathologic features, and postoperative outcomes were determined. Stage-stratified disease-specific mortality was calculated and multivariate analysis performed.
Results
When compared with WMD and PD tumors, SRC tumors were associated with younger age (63 years SRC vs. 71 years WMD and 72 years PD,
p
< 0.0001) and with female sex (58 % SRC vs. 40 % WMD and 40 % PD,
p
= 0.0003). Median follow-up was 115 months. Patients with stage Ia SRC lesions had a better 5-year disease-specific mortality compared with stage-matched intestinal-type tumors (0 % SRC vs. 8 % WMD and 24 % PD,
p
= 0.001). In contrast, SRC patients with stage III disease fared significantly worse (78 % SRC vs. 54 % WMD and 72 % PD,
p
= 0.001). On multivariate analysis, the risk of death from gastric cancer comparing all three groups was lowest for SRC in stage I and highest for SRC in stage III disease (stage III hazard ratio: SRC 1 vs. 0.47 WMD and 0.85 PD).
Conclusions
When compared with intestinal-type tumors, SRC tumors at early stages are not necessarily associated with poor outcomes.
Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4), has been shown to improve survival in patients with advanced metastatic melanoma. It also enhances immunity to ...NY-ESO-1, a cancer/testis antigen expressed in a subset of patients with melanoma. To characterize the association between immune response and clinical outcome, we first analyzed NY-ESO-1 serum antibody by ELISA in 144 ipilimumab-treated patients with melanoma and found 22 of 140 (16%) seropositive at baseline and 31 of 144 (22%) seropositive following treatment. These NY-ESO-1–seropositive patients had a greater likelihood of experiencing clinical benefit 24 wk after ipilimumab treatment than NY-ESO-1–seronegative patients (P = 0.02, relative risk = 1.8, two-tailed Fisher test). To understand why some patients with NY-ESO-1 antibody failed to experience clinical benefit, we analyzed NY-ESO-1–specific CD4+ and CD8+ T-cell responses by intracellular multicytokine staining in 20 NY-ESO-1–seropositive patients and found a surprising dissociation between NY-ESO-1 antibody and CD8 responses in some patients. NY-ESO-1–seropositive patients with associated CD8+ T cells experienced more frequent clinical benefit (10 of 13; 77%) than those with undetectable CD8+ T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), as well as a significant survival advantage (P = 0.01; hazard ratio = 0.2, time-dependent Cox model). Together, our data suggest that integrated NY-ESO-1 immune responses may have predictive value for ipilimumab treatment and argue for prospective studies in patients with established NY-ESO-1 immunity. The current findings provide a strong rationale for the clinical use of modulators of immunosuppression with concurrent approaches to favor tumor antigen-specific immune responses, such as vaccines or adoptive transfer, in patients with cancer.
Background
Age 45 years is used as a cutoff in the staging of well-differentiated thyroid cancer (WDTC) as it represents the median age of most datasets. The aim of this study was to determine a ...statistically optimized age threshold using a large dataset of patients treated at a comprehensive cancer center.
Methods
Overall, 1807 patients with a median follow-up of 109 months were included in the study. Recursive partitioning was used to determine which American Joint Committee on Cancer (AJCC) variables were most predictive of disease-specific death, and whether a different cutoff for age would be found. From the resulting tree, a new age cutoff was picked and patients were restaged using this new cutoff.
Results
The 10-year disease-specific survival (DSS) by Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and 81 % for stages I–IV, respectively. Using recursive partitioning, the presence of distant metastasis was the most powerful predictor of DSS. For M0 patients, age was the next most powerful predictor, with a cutoff of 56 years. For M1 patients, a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55 years was selected as a more robust age cutoff than 45 years. The 10-year DSS by new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for stages I–IV, respectively.
Conclusion
A change in age cutoff in the AJCC/UICC staging for WDTC to 55 years would improve the accuracy of the system and appropriately prevent low-risk patients being overstaged and overtreated.
Anti‐GD2 murine antibody 3F8 plus subcutaneously (sc) administered granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was used against primary refractory neuroblastoma in metastatic ...osteomedullary sites. Large study size and long follow‐up allowed assessment of prognostic factors in a multivariate analysis not reported with other anti‐GD2 antibodies. In a phase II trial, 79 patients without prior progressive disease were treated for persistent osteomedullary neuroblastoma documented by histology and/or metaiodobenzyl‐guanidine (MIBG) scan. In the absence of human antimouse antibody, 3F8 + scGM‐CSF cycles were repeated up to 24 months. Minimal residual disease (MRD) in bone marrow was measured by quantitative reverse transcription‐polymerase chain reaction pre‐enrollment and post‐cycle #2, before initiation of 13‐cis‐retinoic acid. Study endpoints were: (i) progression‐free survival (PFS) compared with the predecessor trial of 3F8 plus intravenously administered (iv) GM‐CSF (26 patients) and (ii) impact of MRD on PFS. Using all 105 patients from the two consecutive 3F8 + GM‐CSF trials, prognostic factors were analyzed by multivariate Cox regression model. Complete response rates to 3F8 + scGM‐CSF were 87% by histology and 38% by MIBG. Five‐year PFS was 24 ± 6%, which was significantly superior to 11 ± 7% with 3F8 + ivGM‐CSF (p = 0.002). In the multivariate analysis, significantly better PFS was associated with R/R or H/R FCGR2A polymorphism, sc route of GM‐CSF and early MRD response. MYCN amplification was not prognostic. Complement consumption was similar with either route of GM‐CSF. Toxicities were manageable, allowing outpatient treatment. 3F8 + scGM‐CSF is highly active against chemoresistant osteomedullary neuroblastoma. MRD response may be an indicator of tumor sensitivity to anti‐GD2 immunotherapy. Correlative studies highlight the antineoplastic potency of myeloid effectors.
What's New?
In high‐risk neuroblastoma, persistence of osteomedullary metastases forebodes poor outcome. Here, in a phase II trial, anti‐GD2 murine antibody 3F8 plus subcutaneously‐administered granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was used against primary refractory neuroblastoma in metastatic osteomedullary sites. The experience documents activity against histologically and/or radiologically‐visible chemoresistant neuroblastoma. Large study size and lengthy follow‐up allow use of prognostic variables (minimal residual disease, MYCN, Fcγ receptors, KIR genotypes of natural killer cells) in a multivariate analysis not described with other anti‐GD2 antibodies. Correlative studies highlight the anti‐neoplastic potency of myeloid effectors rather than lymphocytes, usually the focus in the immunotherapy of solid tumors.
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