Multifaceted effects of obesity on cancer immunotherapies: Bridging preclinical models and clinical data.

Obesity, defined by excessive body fat, is a highly complex condition affecting numerous physiological processes, such as metabolism, proliferation, and cellular homeostasis. These multifaceted effects impact cells and tissues throughout the host, including immune cells as well as cancer biology. Because of the multifaceted nature of obesity, common parameters used to define it (such as body mass index in humans) can be problematic, and more nuanced methods are needed to characterize the pleiotropic metabolic effects of obesity. Obesity is well-accepted as an overall negative prognostic factor for cancer incidence, progression, and outcome. This is in part due to the meta-inflammatory and immunosuppressive effects of obesity. Immunotherapy is increasingly used in cancer therapy, and there are many different types of immunotherapy approaches. The effects of obesity on immunotherapy have only recently been studied with the demonstration of an "obesity paradox", in which some immune therapies have been demonstrated to result in greater efficacy in obese subjects despite the direct adverse effects of obesity and excess body fat acting on the cancer itself. The multifactorial characteristics that influence the effects of obesity (age, sex, lean muscle mass, underlying metabolic conditions and drugs) further confound interpretation of clinical data and necessitate the use of more relevant preclinical models mirroring these variables in the human scenario. Such models will allow for more nuanced mechanistic assessment of how obesity can impact, both positively and negatively, cancer biology, host metabolism, immune regulation, and how these intersecting processes impact the delivery and outcome of cancer immunotherapy.

Scrutinizing the use of contrasted chest CTs in extremity sarcoma staging and surveillance.

BACKGROUND: Since 2015, the American College of Radiology (ACR) has recommended staging for lung metastasis via chest computed tomography (CT) without contrast for extremity sarcoma staging and surveillance. The purpose of this study was to determine our institutional compliance with this recommendation. METHODS: This was a retrospective chart review of patients diagnosed with sarcoma in the extremities who received CT imaging of the chest for pulmonary staging and surveillance at our institution from 2005 to 2023. A total of 1916 CT studies were included for analysis. We scrutinized ordering patterns before and after 2015 based on the ACR-published metastasis staging and screening guidelines. An institutional and patient cost analysis was performed between CT modalities. RESULTS: The prevalence of CT scans ordered and performed with contrast was greater than those without contrast both prior and post-ACR 2015 guidelines. Furthermore, 79.2% of patient's final surveillance CTs after 2015 were performed with contrast. A cost analysis was performed and demonstrated an additional $297 704 in patient and institutional costs. CONCLUSIONS: At our institution, upon review of CT chest imaging for pulmonary staging and surveillance in patients with extremity sarcoma the use of contrast has been routinely utilized despite a lack of evidence for its necessity and contrary to ACR guidelines.

Characterization of natural killer and cytotoxic T-cell immune infiltrates in pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor response to systemic therapies, including immunotherapy. Given the immunotherapeutic potential of natural killer (NK) cells, we evaluated intratumoral NK cell infiltrates along with cytotoxic T cells in PDAC to determine their association with patient outcomes. METHODS: We analyzed tumors from 93 PDAC patients treated from 2012 to 2020. Predictor variables included tumor-infiltrating lymphocytes (TILs), T-cell markers (CD3, CD8, CD45RO), NK marker (NKp46), and NK inhibitory marker (major histocompatibility complex class I [MHC-I]) by immunohistochemistry. Primary outcome variables were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Mean TILs, CD3, and NKp46 scores were 1.3 ± 0.63, 20.6 ± 17.5, and 3.1 ± 3.9, respectively. Higher expression of CD3 and CD8 was associated with higher OS, whereas NK cell infiltration was not associated with either RFS or OS. There was a tight positive correlation between MHC-I expression and all T-cell markers, but not with NKp46. CONCLUSIONS: Overall NK cell infiltrates were low in PDAC and did not predict clinical outcomes, whereas T-cell infiltrates did. Further characterization of the immune infiltrate in PDAC, including inhibitory signals and suppressive cell types, may yield better biomarkers of prognosis and immune targeting in this refractory disease.

Low-Dose Sorafenib Promotes Cancer Stem Cell Expansion and Accelerated Tumor Progression in Soft Tissue Sarcomas.

The cancer stem cell (CSC) hypothesis postulates that heterogeneous human cancers harbor a population of stem-like cells which are resistant to cytotoxic therapies, thus providing a reservoir of relapse following conventional therapies like chemotherapy and radiation (RT). CSCs have been observed in multiple human cancers, and their presence has been correlated with worse clinical outcomes. Here, we sought to evaluate the impact of drug dosing of the multi-tyrosine kinase inhibitor, sorafenib, on CSC and non-CSCs in soft tissue sarcoma (STS) models, hypothesizing differential effects of sorafenib based on dose and target cell population. In vitro, human cancer cell lines and primary STS from surgical specimens were exposed to escalating doses of sorafenib to determine cell viability and expression of CSC marker aldehyde dehydrogenase (ALDH). In vivo, ALDHbright CSCs were isolated, exposed to sorafenib, and xenograft growth and survival analyses were performed. We observed that sarcoma CSCs appear to paradoxically respond to the tyrosine kinase inhibitor sorafenib at low doses with increased proliferation and stem-like function of CSCs, whereas anti-viability effects dominated at higher doses. Importantly, STS patients receiving neoadjuvant sorafenib and RT on a clinical trial (NCT00864032) showed increased CSCs post therapy, and higher ALDH scores post therapy were associated with worse metastasis-free survival. These data suggest that low-dose sorafenib may promote the CSC phenotype in STS with clinically significant effects, including increased tumor growth and higher rates of metastasis formation in sarcoma patients.

Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models. Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD. Importantly, double cytokine blockade preserved GVT effects reinforcing that GVT and GVHD can be delineated and may result in greater efficacy in allo-HSCT.

Sarcopenia and frailty as predictors of surgical morbidity and oncologic outcomes in retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors for which surgical resection is the principal treatment. There is no established model to predict perioperative risks for RPS. We evaluated the association between preoperative sarcopenia, frailty, and hypoalbuminemia with surgical and oncological outcomes. METHODS: We performed a prospective cohort analysis of 65 RPS patients who underwent surgical resection. Sarcopenia was defined as Total Psoas Area Index ≤ 1st quintile by sex. Frailty was estimated using the modified frailty index (mFI). Logistic regression models were used to assess predictors of 30-day postoperative morbidity. The Kaplan-Meier method with log-rank test was utilized to assess factors associated with overall (OS) and recurrence-free survival (RFS). RESULT: Sarcopenia was associated with worse OS with a median of 54 compared with 158 months (p = 0.04), but no differences in RFS (p > 0.05). Hypoalbuminemia was associated with worse OS with a median of 72 compared with 158 months (p < 0.01). MFI scores were not associated with OS or RFS (p > 0.05). Sarcopenia, mFI, and hypoalbuminemia were not associated with postoperative morbidity (p > 0.05). CONCLUSION: This study suggests that sarcopenia may be utilized as a measure of overall fitness, rather than a cancer-specific risk, and the mFI is a poor predictive measure of outcomes in RPS.

Chemotherapy After Diagnosis of Malignant Bowel Obstruction is Associated with Superior Survival for Medicare Patients with Advanced Malignancy.

BACKGROUND: Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival. METHODS: This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival. RESULTS: Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86-1.07; p = 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00-1.26; p = 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p < 0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65-3.34; p < 0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04-5.14; p < 0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p < 0.05). CONCLUSIONS: Chemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.

The Role of Radiation Therapy in Addition to Lumpectomy and Hormone Therapy in Men 70 Years of Age and Older with Early Breast Cancer: A NCDB Analysis.

PURPOSE: Current treatment guidelines for male breast cancer are guided by female-only trials despite data suggesting distinct clinicopathologic differences between sexes. We sought to evaluate whether radiation therapy (RT) after lumpectomy was associated with equivalent survival among men > 70 years of age with stage I, estrogen receptor (ER) positive tumors, as seen in women from the Cancer and Leukemia Group B (CALGB) 9343 trial. METHODS: We performed a retrospective analysis of 752 stage I, ER-positive male breast cancer patients ≥ 70 years who were treated with hormone therapy and surgery, with or without RT, from the National Cancer Database between 2004 and 2014. Patients were categorized based on surgery and RT (lumpectomy alone, lumpectomy with RT, and mastectomy alone). Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups. RESULTS: Most patients underwent total mastectomy, with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.7% received adjuvant RT. In multivariate analysis, there was no statistical difference in overall survival when comparing lumpectomy alone and lumpectomy with RT (aHR 0.72 [95% CI 0.38-1.37], p = 0.31) or when comparing lumpectomy (alone or with RT) and mastectomy (aHR 1.28 [95% CI 0.88-1.87], p = 0.20). CONCLUSIONS: In this national sample of elderly men with ER-positive early-stage disease treated with endocrine therapy, there were no significant differences in overall survival when comparing lumpectomy alone and lumpectomy with RT, or lumpectomy (alone or with RT) and mastectomy. These results suggest that less aggressive treatment may be appropriate for a subset of male breast cancer patients.

Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).

BACKGROUND: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking. METHODS: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011. Uni- and multivariable logistic models were fitted to study the association between major (Clavien-Dindo grade ≥ 3) complications and patient/surgery characteristics as well as outcome. The resected organ score, a method of standardizing the number of organs resected, as previously described by the TARPSWG, was used. RESULTS: The 681 patients in this study had a median age of 59 years, and 51.8% were female. The most common histologic subtype was de-differentiated liposarcoma (43%), the median resected organ score was 1, and 83.3% of the patients achieved an R0 or R1 resection. Major complications occurred for 16% of the patients, and the 90-day mortality rate was 0.4%. In the multivariable analysis, a transfusion requirement was found to be a significant predictor of major complications (p < 0.001) and worse overall survival (OS) (p = 0.010). However, having a major complication was not associated with a worse OS or a higher incidence of local recurrence or distant metastasis. CONCLUSIONS: A surgical approach to recurrent RPS is relatively safe and comparable with primary RPS in terms of complications and postoperative mortality when performed at specialized sarcoma centers. Because alternative effective therapies still are lacking, when indicated, resection of a recurrent RPS is a reasonable option. Every effort should be made to minimize the need for blood transfusions.

Analysis of Differentiation Changes and Outcomes at Time of First Recurrence of Retroperitoneal Liposarcoma by Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

BACKGROUND: Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differentiated (WD) and dedifferentiated (DD) RLPS are distinct entities with differing outcomes. A few reports suggest that WDLPS can recur as DDLPS and that DDLPS can recur as WDLPS. This study evaluates whether this change in differentiation from the primary tumor to the first local recurrence impacts long-term outcomes. METHODS: Retrospective review from 22 sarcoma centers identified consecutive patients who underwent resection for a first locally recurrent RLPS from January 2002 to December 2011. Outcomes measured included overall survival, local recurrence, and distant metastasis. RESULTS: A total of 421 RPLS patients were identified. Of the 230 patients with primary DDLPS, 34 (15%) presented WDLPS upon recurrence (DD → WD); and of the 191 patients with primary WDLPS, 54 (28%) presented DDLPS upon recurrence (WD → DD). The 6-year overall survival probabilities (95% CI) for DD → DD, DD → WD, WD → WD, and WD → DD were 40% (32-48%), 73% (58-92%), 76% (68-85%), and 56% (43-73%) (p < 0.001), respectively. The 6-year second local recurrence incidence was 66% (59-73%), 63% (48-82%), 66% (57-76%), and 77% (66-90%), respectively. The 6-year distant metastasis incidence was 13% (9-19%), 3% (0.4-22%), 5% (2-11%), and 4% (1-16%), respectively. On multivariable analysis, DD → WD was associated with improved overall survival when compared with DD → DD (p < 0.001). Moreover, WD → DD was associated with a higher risk of LR (p = 0.025) CONCLUSION: A change in RLPS differentiation from primary tumor to first local recurrence appears to impact survival. These findings may be useful in counseling patients on their prognosis and subsequent management.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Surgical and oncologic outcomes following arterial resection and reconstruction for advanced solid tumors.

BACKGROUND AND OBJECTIVES: Although arterial involvement for advanced tumors is rare, vascular resection may be indicated to achieve complete tumor resection. Given the potential morbidity of this approach, we sought to evaluate perioperative outcomes, vascular graft patency, and survival among patients undergoing tumor excision with en bloc arterial resection and reconstruction. METHODS: From 2010 to 2020, we identified nine patients with tumors encasing or extensively abutting major arterial structures for whom en bloc arterial resection and reconstruction was performed. RESULTS: Mean age was 53 ± 20 years, and 89% were females. Diagnoses were primary sarcomas (5), recurrent gynecologic carcinomas (3), and benign retroperitoneal fibrosis (1). Tumors involved the infrarenal aorta (2), iliac arteries (6), and superficial femoral artery (1). Three patients (33%) had severe perioperative morbidity (Grade III + ) with no mortality. At a median follow-up of 23 months, eight patients (89%) had primary graft patency, and five patients (56%) had no evidence of disease. CONCLUSIONS: Arterial resection and reconstruction as part of the multimodality treatment of regionally advanced tumors is associated with acceptable short- and long-term outcomes, including excellent graft patency. In appropriately selected patients, involvement of major arterial structures should not be viewed as a contraindication to attempted curative surgery.

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

BACKGROUND: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). METHODS: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. RESULTS: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. CONCLUSIONS: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.

Radiotherapy is Associated With Improved Survival in Patients With Synovial Sarcoma Undergoing Surgery: A National Cancer Database Analysis.

BACKGROUND: Previous studies have demonstrated an association of perioperative radiotherapy (RT) with improved survival in patients with synovial sarcoma (SS) undergoing surgery, but the mechanism for this is unknown. In this study, we sought to further analyze this association using a hospital-based data set where data on chemotherapy administration and surgical margin status are available. METHODS: Using the National Cancer Database, we identified 1216 patients with SS (aged ≥18 y) from 2004-2012 undergoing surgery. Cox proportional hazards analysis was used to study the effect of clinicopathologic variables on overall survival (OS). RESULTS: Mean age at diagnosis was 41.5 y (range 18-90), and 71.3% of tumors were high grade; 22.9% underwent surgery alone, 59.6% received RT with surgery, 44.2% received chemotherapy with surgery, and 26.3% received trimodality therapy. Age, sex, grade, Charlson-Deyo score, and RT (hazard ratio, 0.676; 95% confidence interval, 0.519-0.880; P = 0.004) were associated with improved OS, whereas chemotherapy (hazard ratio, 1.20; 95% confidence interval, 0.899-1.60; P = 0.217) and surgical margin status were not. Trimodality therapy with surgery, RT, and chemotherapy was associated with improved OS when compared with therapy with surgery and chemotherapy alone. CONCLUSIONS: In patients with SS undergoing surgery, we observed a significant improved association of OS with the addition of RT when adjusting for comorbidity score, margin status, and receipt of chemotherapy. These data further support routine implementation of RT in the treatment of patients with SS, including those receiving aggressive multimodality and trimodality care.

Opportunistic muscle measurements on staging chest CT for extremity and truncal soft tissue sarcoma are associated with survival.

BACKGROUND AND OBJECTIVES: Computed tomography (CT) measurements of sarcopenia have been proposed as biomarkers associated with outcomes in various cancers and have typically been evaluated at the L3 vertebral level. However, staging imaging for patients with extremity and truncal soft tissue sarcoma (STS) often only includes chest CT imaging which precludes evaluation at L3. Therefore, we sought to evaluate muscle metrics at T12 on standard staging chest CT scans and evaluate for correlation with overall and event-free survival in patients with STS. METHODS: CT chest imaging for 89 patients with intermediate and high-grade STS (53 male, 36 female; 58.5 ± 19.0 years old, follow-up 37.4 ± 27.1 months) was reviewed on PACS at T12 for skeletal muscle density (SMD) and skeletal muscle index (SMI). RESULTS: Overall survival increased with increased SMD on univariate (hazard ratio [HR] = 0.61 [0.43, 0.86]) and age-adjusted analysis (HR = 0.65 [0.42, 0.89]. Event-free survival also increased with increased SMD in univariate analyses (HR = 0.68 [0.49, 0.95]) but did not maintain significance after adjusting for age (HR = 0.68 [0.43, 1.07]). SMI was not a predictor of overall or event-free survival. CONCLUSIONS: Higher SMD measured on routinely obtained staging chest CTs in STS patients is associated with improved survival.

Is Breast-Conserving Therapy Appropriate for Male Breast Cancer Patients? A National Cancer Database Analysis.

BACKGROUND: Current treatment guidelines for male breast cancer are predominantly guided by female-only clinical trials. With scarce research, it is unclear whether breast-conserving therapy (BCT) is equivalent to mastectomy in men. We sought to compare overall survival (OS) among male breast cancer patients who underwent BCT versus mastectomy. METHODS: We performed a retrospective analysis of 8445 stage I-II (T1-2 N0-1 M0) male breast cancer patients from the National Cancer Database (2004-2014). Patients were grouped according to surgical and radiation therapy (RT). BCT was defined as partial mastectomy followed by RT. Multivariable and inverse probability of treatment-weighted (IPTW) Cox proportional hazards models were used to compare OS between treatment groups, controlling for demographic and clinicopathologic characteristics. RESULTS: Most patients underwent total mastectomy (61.2%), whereas 18.2% underwent BCT, 12.4% underwent total mastectomy with RT, and 8.2% underwent partial mastectomy alone. In multivariable and IPTW models, partial mastectomy alone, total mastectomy alone, and total mastectomy with RT were associated with worse OS compared with BCT (p < 0.001 all). Ten-year OS was 73.8% for BCT and 56.3, 58.0 and 56.3% for other treatment approaches. Older age, higher T/N stage, histological grade, and triple-negative receptor status were associated with poorer OS (p < 0.05). Subgroup analysis by stage demonstrated similar results. CONCLUSIONS: In this national sample of male breast cancer patients, BCT was associated with greater survival. The underlying mechanisms of this association warrant further study, because more routine adoption of BCT in male breast cancer appears to translate into clinically meaningful improvements in survival.

Clinical Outcomes and Costs Following Unplanned Excisions of Soft Tissue Sarcomas in the Elderly.

BACKGROUND: Surgical guidelines for soft tissue sarcoma (STS) emphasize pretreatment evaluation and reports of the perils of unplanned excision exist. Given the paucity of population-based data on this topic, our objective was to analyze clinical outcomes and costs of planned versus unplanned STS excisions in the Medicare population. METHODS: We analyzed 3913 surgical patients with STS ≥66 y old from 1992 to 2011 using the Surveillance, Epidemiology, and End Results-Medicare datafiles. Planned excisions were classified based on preoperative MRI and/or biopsy, whereas unplanned excisions were classified by excision as the first procedure. Inverse probability of treatment weighting with propensity scores was used to adjust for clinicopathologic differences. Re-excisions, complications, and Medicare payments were compared with multivariate models. Overall survival and disease-specific survival were analyzed using Cox proportional hazards and competing risk models. RESULTS: Before the first excision, 24.3% had an MRI and biopsy, 27.3% had an MRI, 11.4% had a biopsy, and 36.9% were unplanned. Re-excision rates were highest for unplanned excisions: 46.3% compared to 18.1%, 36.4%, and 29.7% for other groups (P < 0.0001). There was no difference in disease-specific survival or overall survival between groups (P > 0.05). Planned excisions were associated with increased Medicare costs (P < 0.05), with the first resection contributing to the majority of costs. Subgroup analyses by histologic grade and tumor size revealed similar results. CONCLUSIONS: Survival was comparable with greater health care costs in elderly patients undergoing planned STS excision. Although unplanned excisions remain a quality of care issue with high re-excision rates, these data have important implications for the surgical management of STS in the elderly.

Extremity soft tissue sarcoma in the elderly: Are we overtreating or undertreating this potentially vulnerable patient population?

BACKGROUND: As the U.S. population ages, differences in oncologic outcomes among the elderly have been recognized. Our objective was to analyze the clinical, pathologic, and treatment outcomes for elderly soft tissue sarcoma (STS) patients, hypothesizing significant differences in the management and response to therapy. METHODS: Using the National Cancer Database, we identified 33 859 patients with nonmetastatic extremity STS. We defined elderly as ≥74 years in age and compared patient and treatment variables between adult and elderly patients. Cox-proportional hazards analysis was used to determine predictors of overall survival (OS). RESULTS: We identified 8504 elderly patients. Significant differences in histologic subtype, grade, and facility type between elderly and nonelderly patients (P < 0.05) exist. Elderly patients were less likely to undergo R0 resection (P = 0.001) and had a higher 90-day mortality (P = 0.001). Surgical elderly patients experienced superior OS compared with nonsurgical patients (P = 0.001). Among elderly patients, younger age, and female sex, lower Charlson-Deyo score, lower grade, smaller tumors, surgical resection, negative surgical margins, and radiation therapy were associated with better OS. CONCLUSIONS: Key differences exist in elderly extremity STS patients, including a narrower benefit/risk ratio with surgical management. These data highlight that elderly patients represent a distinct cohort for whom more careful selection appears indicated.

Morbidity, mortality and temporal trends in the surgical management of retroperitoneal sarcoma: An ACS-NSQIP follow up analysis.

BACKGROUND: Calls for multivisceral resection (MVR) of retroperitoneal sarcoma (RPS) are increasing, although the risks and benefits remain controversial. We sought to analyze current 30-day morbidity and mortality rates, and trends in utilization of MVR in a national database. METHODS: Overall morbidity, severe morbidity, mortality rates, and temporal trends were analyzed utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). RESULTS: From 2012 to 2015, a total of 564 patients underwent RPS resection with 233 patients (41%) undergoing MVR. The MVR group had a higher rate of preoperative weight loss and larger tumors overall. When comparing MVR to non-MVR, there was no significant difference in overall morbidity (22% vs 17%, P = .13), severe morbidity (11% vs 8%, P = .18), or mortality (<1% vs 2%, P = .25). On multivariate analysis, MVR was not associated with increased overall morbidity or severe morbidity. Mortality rates were too low for meaningful statistical analysis. Annual rates of MVR ranged from 37% to 46% with no significant change over time (P = .47). RESULTS: Short-term morbidity and mortality rates after MVR for RPS remain acceptable, but rates of MVR show little change over time in NSQIP hospitals. Concerns about increased morbidity and mortality should not be viewed as a contraindication to wider implementation of MVR for RPS.

Drivers of Cost for Pancreatic Surgery: It's Not About Hospital Volume.

BACKGROUND: Outcomes for pancreatic resection have been studied extensively due to the high morbidity and mortality rates, with high-volume centers achieving superior outcomes. Ongoing investigations include healthcare costs, given the national focus on reducing expenditures. Therefore, we sought to evaluate the relationships between pancreatic surgery costs with perioperative outcomes and volume status. METHODS: We performed a retrospective analysis of 27,653 patients who underwent elective pancreatic resections from October 2013 to June 2017 using the Vizient database. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation. Generalized linear modeling adjusting for demographic, clinical, and operation characteristics was performed to assess the relationships between cost and length of stay, complications, in-hospital mortality, readmissions, and hospital volume. High-volume centers were defined as hospitals performing ≥ 19 operations annually. RESULTS: The unadjusted mean cost for pancreatic resection and corresponding hospitalization was $20,352. There were no differences in mean costs for pancreatectomies performed at high- and low-volume centers [- $1175, 95% confidence interval (CI) - $3254 to $904, p = 0.27]. In subgroup analysis comparing adjusted mean costs at high- and low-volume centers, there was no difference among patients without an adverse outcome (- $99, 95% CI - $1612 to 1414, p = 0.90), one or more adverse outcomes (- $1586, 95% CI - $4771 to 1599, p = 0.33), or one or more complications (- $2835, 95% CI - $7588 to 1919, p = 0.24). CONCLUSIONS: While high-volume hospitals have fewer adverse outcomes, there is no relationship between surgical volume and costs, which suggests that, in itself, surgical volume is not an indicator of improved healthcare efficiency reflected by lower costs. Patient referral to high-volume centers may not reduce overall healthcare expenditures for pancreatic operations.