Current Management of Desmoid Tumors: A Review.

Importance: Desmoid tumor (DT) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Previously, surgery was the standard primary treatment modality; however, within the past decade, a paradigm shift toward less-invasive management has been introduced and an effort to harmonize the strategy among clinicians has been made. To update the 2020 global evidence-based consensus guideline on the management of patients with DT, the Desmoid Tumor Working Group convened a 1-day consensus meeting in Milan, Italy, on June 30, 2023, under the auspices of the European Reference Network on Rare Adult Solid Cancers and Sarcoma Patient Advocacy Global Network, the Desmoid Foundation Italy, and the Desmoid Tumor Research Foundation. The meeting brought together over 90 adult and pediatric sarcoma experts from different disciplines as well as patients and patient advocates from around the world. Observations: The 2023 update of the global evidence-based consensus guideline focused on the positioning of local therapies alongside surgery and radiotherapy in the treatment algorithm as well as the positioning of the newest class of medical agents, such as γ-secretase inhibitors. Literature searches of MEDLINE and Embase databases were performed for English-language randomized clinical trials (RCTs) of systemic therapies to obtain data to support the consensus recommendations. Of the 18 full-text articles retrieved, only 4 articles met the inclusion criteria. The 2023 consensus guideline is informed by a number of new aspects, including data for local ablative therapies such as cryotherapy; other indications for surgery; and the γ-secretase inhibitor nirogacestat, the first representative of the newest class of medical agents and first approved drug for DT. Management of DT is complex and should be carried out exclusively in designated DT referral centers equipped with a multidisciplinary tumor board. Selection of the appropriate strategy should consider DT-related symptoms, associated risks, tumor location, disease morbidities, available treatment options, and preferences of individual patients. Conclusions and Relevance: The therapeutic armamentarium of DT therapy is continually expanding. It is imperative to carefully select the management strategy for each patient with DT to optimize tumor control and enhance quality of life.

Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. METHODS: From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. RESULTS: Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. CONCLUSION: For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

Simple Preoperative Imaging Measurements Predict Postoperative Pancreatic Fistula After Pancreatoduodenectomy.

OBJECTIVE: Postoperative pancreatic fistula is a potentially devastating complication after pancreatoduodenectomy (PD). The purpose of this study was to identify features on preoperative computed tomography (CT) imaging that correlate with an increased risk of postoperative pancreatic fistula (POPF). METHODS: Patients who underwent PD at our high-volume pancreatic surgery center from 2019 to 2021 were included if CT imaging was available within 8 weeks of surgical intervention. Pancreatic neck thickness (PNT), abdominal wall thickness (AWT), and intra-abdominal distance from pancreas to peritoneum (PTP) were measured by two board-certified radiologists who were blinded to the clinical outcomes. Radiographic measurements, as well as preoperative patient characteristics and intraoperative data, were assessed with univariate and multivariable analysis (MVA) to determine risk for clinically relevant POPF (CR-POPF, grades B and C). RESULTS: A total of 204 patients met inclusion criteria. Median PTP was 5.8 cm, AWT 1.9 cm, and PNT 1.3 cm. CR-POPF occurred in 33 of 204 (16.2%) patients. MVA revealed PTP > 5.8 cm (odds ratio [OR] 2.86, p = 0.023), PNT > 1.3 cm (OR 2.43, p = 0.047), soft pancreas consistency (OR 3.47, p = 0.012), and pancreatic duct size ≤ 3.0 mm (OR 4.55, p = 0.01) as independent risk factors for CR-POPF after PD. AWT and obesity were not associated with increased risk of CR-POPF. Patients with PTP > 5.8 cm or PNT > 1.3 cm were significantly more likely to suffer a major complication after PD (39.6% vs. 22.3% and 40% vs. 22.1%, p < 0.008). CONCLUSIONS: Patients with a thick pancreatic neck and increased intra-abdominal girth have a heightened risk of CR-POPF after pancreatoduodenectomy, and they experience more serious postoperative complications. We defined a simple CT scan-based measurement tool to identify patients at increased risk of CR-POPF.

Early experience with robotic central pancreatectomy with patient-reported outcomes and comparison with open central pancreatectomy.

BACKGROUND: Robotic central pancreatectomy (CP) has emerged in recent years as a noninferior approach to open CP and may offer improved patient-reported outcomes and reduction in incisional hernias. METHODS: All patients who underwent open and robotic CP between (2013 and 2022) were selected, and perioperative outcomes were analyzed. Patients who underwent robotic CP were interviewed over the phone to assess patient-reported postoperative outcomes. RESULTS: A total of 18 CP operations (56%-open vs. 44%-robotic) were identified. The overall median age was 67 years (interquartile range: 60-72), and 50% (n = 9) of patients were female. Median length of surgery was statistically longer for robotic CP (411 vs. 138 min, p = 0.002); all other intraoperative variables were similar. Postoperatively, a similar number of patients in the open and robotic cohorts developed clinically significant postoperative pancreatic fistulas (37.5% vs. 30%, p = 1) and major complications (37.5% vs. 20%, p = 0.60), respectively. No patients in the robotic cohort developed an incisional hernia, compared to 40% (n = 4) in open (p = 0.08). All patients returned to a baseline level of activity and reported a high quality of life. CONCLUSION: With the exception of longer operative times, robotic CP is a noninferior, definitive resection technique for select lesions of the middle pancreas. Additionally, the robotic approach may result in a reduction in incisional hernia development.

Complex Vascular Resections for Retroperitoneal Soft Tissue Sarcoma.

Retroperitoneal sarcomas (RPSs) are locally aggressive tumors that can compromise major vessels of the retroperitoneum including the inferior vena cava, aorta, or main tributary vessels. Vascular involvement can be secondary to the tumor's infiltrating growth pattern or primary vascular origin. Surgery is still the mainstay for curing this disease, and resection of RPSs may include major vascular resections to secure adequate oncologic results. Our improved knowledge in the tumor biology of RPSs, in conjunction with the growing surgical expertise in both sarcoma and vascular surgical techniques, has allowed for major vascular reconstructions within multi-visceral resections for RPSs with good perioperative results. This complex surgical approach may include the combined work of various surgical subspecialties.

Response Evaluation of Neoadjuvant Therapies in Sarcoma.

OPINION STATEMENT: Sarcoma is a complex and heterogeneous disease with a rapidly evolving treatment landscape. With a growing emphasis on neoadjuvant therapy as a way to improve surgical and oncologic outcomes, our approach to monitor treatment efficacy must also continue to evolve. This is paramount to both clinical trial design, where endpoints must accurately reflect disease outcomes, and individual patient, whose treatment response informs therapeutic decisions. In the era of personalized medicine, the response to neoadjuvant treatment in sarcoma remains most effectively gauged by pathologic review following surgical resection. Although measures of pathologic complete response most effectively predict outcome, the requisite surgical excision precludes their use in real-time monitoring of neoadjuvant treatment response. Current image-based metrics such as RECIST and PERCIST have been utilized in many trials; however, they are limited by their unilateral measurement approach. More effective tools are needed to better measure the response to therapy prior to neoadjuvant regimen completion, so that the medication or regimen may be best tailored to patient response in an ongoing fashion. Delta-radiomics and circulating tumor DNA (ctDNA) represent promising novel tools for real-time monitoring of treatment efficacy. These metrics have been shown to predict pathologic complete response and disease progression at a superior level to traditional CT-based guidelines. Delta-radiomics is currently being utilized in a clinical trial among soft tissue sarcoma patients in which radiation dosage is adjusted based on radiomic data. The ability of ctDNA to detect molecular residual disease is also under study in multiple clinical trials, although none in the field of sarcoma. Future directions in the field include the use of ctDNA and molecular residual disease testing among sarcoma patients, as well as increased utilization of delta-radiomics, to more effectively monitor neoadjuvant treatment response prior to surgical resection.

Management of recurrent retroperitoneal sarcomas.

Recurrent retroperitoneal sarcomas are rare, with patterns of recurrence determined by the histologic subtype. A range of patient characteristics and treatment profiles combined with a myriad of presentations and clinical courses of recurrences make this diverse entity challenging to manage. Although surgical resection improves survival in select patients, the oncological outcomes are inferior to that of primary retroperitoneal sarcomas. Management options for unresectable disease include local ablative therapy, radiation and systemic therapy, with palliative surgery indicated occasionally. Attempts at disease control must be balanced with potential morbidity and impact on the patient's quality of life. This review aims to offer insights into the current understanding of recurrent retroperitoneal sarcomas and provide some guidance on management.

Recovery of Patient-reported Quality of Life After Esophagectomy.

BACKGROUND: Esophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life (QOL). Patient-reported outcomes (PROs) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PROs in the first year after esophagectomy. METHODS: Longitudinal QOL scores measuring physical function, pain, and dyspnea were obtained from esophagectomy patients during all clinic visits. PRO scores were obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System from April 2018 to February 2021. Mean PRO scores over 100 days after surgery were compared with baseline PRO scores using mixed-effects modeling with compound symmetry correlational structure. RESULTS: One hundred three patients with PRO results were identified. Reasons for esophagectomy were malignancy (87.4%), achalasia (5.8%), stricture (5.8%), and dysplasia (1.0%). When comparing mean PRO scores at visits ≤ 50 days after surgery with preoperative PRO scores, physical function scores declined by 27.3% (P < .001), whereas dyspnea severity and pain interference scores had increased by 24.5% (P < .001) and 17.1% (P < .001), respectively. Although recovery occurred over the course of the 100 days after surgery, mean physical function scores and dyspnea scores were still 12.7% (P = .02) and 26.4% (P = .001) worse, respectively, than mean preoperative levels. CONCLUSIONS: Despite declines in QOL scores immediately after esophagectomy, recovery back toward baseline was observed during the first 100 days. These findings are of considerable importance when counseling patients regarding esophagectomy, tracking recovery, and implementing quality improvement initiatives. Further long-term follow-up is needed to determine recovery beyond 100 days.

Outcomes of plastic surgical reconstruction in extremity and truncal soft tissue sarcoma: Results from the US Sarcoma Collaborative.

BACKGROUND: This study aimed to define how utilization of plastic surgical reconstruction (PSR) affects perioperative outcomes, locoregional recurrence-free survival (LRRFS), and overall survival (OS) after radical resection of extremity and truncal soft tissue sarcoma (ETSTS). The secondary aim was to determine factors associated with PSR. METHODS: Patients who underwent resection of ETSTS between 2000 and 2016 were identified from a multi-institutional database. PSR was defined as complex primary closure requiring a plastic surgeon, skin graft, or tissue-flap reconstruction. Outcomes included PSR utilization, postoperative complications, LRRFS, and OS. RESULTS: Of 2750 distinct operations, 1060 (38.55%) involved PSR. Tissue-flaps (854, 80.57%) were most commonly utilized. PSR was associated with a higher proportion of R0 resections (83.38% vs. 74.42%, p < 0.001). Tissue-flap PSR was associated with local wound complications (odds ratio: 1.81, confidence interval: 1.21-2.72, p = 0.004). Neither PSR nor postoperative complications were independently associated with LRRFS or OS. High-grade tumors (1.60, 1.13-2.26, p = 0.008) and neoadjuvant radiation (1.66, 1.20-2.30, p = 0.002) were associated with the need for PSR. CONCLUSION: Patients with ETSTS undergoing resection with PSR experienced acceptable rates of complications and a higher rate of negative margins, which were associated with improved LRRFS and OS. High tumor grade and neoadjuvant radiation were associated with requirement of PSR.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Resection of retroperitoneal tumors with inferior vena cava involvement without caval reconstruction.

BACKGROUND AND OBJECTIVES: Retroperitoneal tumors with involvement of the inferior vena cava (IVC) often require resection of the IVC to achieve complete tumor removal. This study evaluates the safety and efficacy of IVC ligation without caval reconstruction. METHODS: A retrospective chart review of patients who underwent IVC ligation (IVC-Ligation) and IVC resection with reconstruction (IVC-Reconstruction) at our institution between May 2004 and April 2021 was performed. Outcomes from the two surgical techniques were compared via univariate analysis using the Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Forty-nine IVC-Ligation and six IVC-Reconstruction surgeries were identified. There were no differences in baseline demographics, tumor characteristics, complication rates, postoperative morbidity, or overall 5-year survival between groups. IVC-Reconstruction patients were more likely to require intensive care unit admission (83% vs. 33%; p = 0.0257) and the IVC-Ligation cohort had a tendency to present with nondebilitating postoperative lymphedema (35% vs. 0%; p = 0.1615), which resolved for most patients. CONCLUSIONS: IVC-Ligation is a viable surgical option for select patients presenting with retroperitoneal tumors with IVC involvement and provides acceptable short- and medium-term outcomes.

Retroperitoneal Sarcomas: Histology Is Everything.

Retroperitoneal sarcomas (RPS) are a rare subset of soft tissue sarcoma that are composed of only a few histologic subtypes, each with a distinct tumor biology, clinical presentation, preferred treatment strategy, recurrence risk, and surveillance plan. In the modern era of precision medicine, our understanding of the implications of subtype tumor biology and anatomic location has led to a more nuanced, histology-specific approach to therapy, including surgery, neoadjuvant radiation therapy, and/or chemotherapy. This article provides a summary of recent updates to the management of RPS.

Extraskeletal myxoid chondrosarcoma: Clinicopathological features and outcomes from the United States sarcoma collaborative database.

BACKGROUNDS AND OBJECTIVES: This investigation described clinicopathological features and outcomes of extraskeletal myxoid chondrosarcoma (EMC) patients. METHODS: EMC patients were identified from the United States Sarcoma Collaborative database between 2000 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and prognostic factors were analyzed. RESULTS: Sixty individuals with a mean age of 55 years were included, and 65.0% (n = 39) were male. 73.3% (n = 44) had a primary tumor. A total of 41.6% (n = 25) developed tumor relapse following resection. The locoregional recurrence rate was 30.0% (n = 18/60), and mean follow-up was 42.7 months. The 5-year OS was 71.0%, while the 5-year RFS was 41.4%. On multivariate analysis for all EMC, chemotherapy (hazard ratio [HR], 6.054; 95% confidence interval [CI], 1.33-27.7; p = 0.020) and radiation (HR, 5.07, 95% CI, 1.3-20.1; p = 0.021) were independently predictive of a worse RFS. Among patients with primary EMC only, the 5-year OS was 85.3%, with a 30.0% (n = 12) locoregional recurrence rate, though no significant prognostic factors were identified. CONCLUSIONS: Long-term survival with EMC is probable, however there exists a high incidence of locoregional recurrence. While chemotherapy and radiation were associated with a worse RFS, these findings were likely confounded by recurrent disease as significance was lost in the primary EMC-only subset.

Management of Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genomically complex tumors commonly diagnosed in the extremities or trunk of elderly patients. They likely represent a spectrum of disease differentiated by myxoid stroma and curvilinear vessels observed in MFS but not in UPS. Limb-sparing surgery is the standard of care although the infiltrative nature of MFS mandates wider resection margins than are necessary for UPS. UPS are conversely associated with high risks of distal recurrence, often prompting recommendations for adjuvant chemotherapy. In both histologies, anthracycline-based therapies or gemcitabine and docetaxel are used to manage advanced disease; immunotherapy may be of benefit in a subset of patients.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.