On the Origin of Abdominal Venous Leiomyosarcomas: The Role of the Sex-Hormone Drainage Pathways.

Background: We hypothesized that abdominal venous leiomyosarcoma (AV-LMS) disproportionately originates in veins of the sex-hormone drainage pathway (SHDP). Our purpose was to classify the anatomical origin of AV-LMS in a large cohort using imaging and explore prognostic implications. Methods: A retrospective review of imaging of all patients presenting with abdominal non-uterine LMS at a single tertiary oncology center was performed. Inclusion criteria were a biopsy-proven LMS of non-uterine abdominal/pelvic origin with pretreatment enhanced computed tomography (CT)/magnetic resonance imaging (MRI). Patients with uterine LMS or prior radiation were excluded. LMS site of origin was assigned by one expert radiologist and indeterminate sites were reviewed with a second external expert radiologist. Locations of inferior vena cava (IVC) tumors were subclassified based on a modification of prior literature. SHDP was defined as originating from ovarian/testicular vein, distal left renal vein, adrenal vein or mid-IVC (IIA). Results: One hundred fifty-five (155) patients were included (92/152 (61%) female) with distant metastases found at presentation in 23/155 (14.8%). Most common organs of origins were veins (84/152, 55.3%), gastrointestinal (24, 15.8%), genital (11, 7.2%) and paratesticular/spermatic cord (11, 7.2%). For venous LMS, the adrenal (both sexes), mid-IVC (IVC IIA, females) and ovarian veins had the highest relative predilection for abdominal non-uterine LMS. Eighty-four (84/152, 55.3%) of tumors were SHDP. On multivariable analysis, both size and SHDP were significant predictors of distant metastases at presentation (P = 0.01), while sex, age, organ system/site and grade were not. Conclusions: For both sexes, tumors arising from SHDP constitute the majority of AV-LMS and may impart a significantly lower risk of metastatic disease at presentation. Among veins, the adrenal veins had the highest predilection for LMS.

Pleomorphic Liposarcoma of the Extremity and Trunk: Multimodality Therapy for Some but Not All?

BACKGROUND: Pleomorphic liposarcoma (PLPS) is an ultra-rare malignancy distinct from well-differentiated/dedifferentiated and myxoid liposarcoma. In this study, we sought to (1) assess outcomes after surgery for primary, non-metastatic PLPS and (2) explore potential indications for multimodality therapy. METHODS: Clinicopathologic data were retrospectively collected for patients treated from 2002 to 2019 at our sarcoma referral center. Descriptive data were summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR), and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest on outcome. RESULTS: Forty-four pathology-verified PLPS cases were included in this study. Median tumor size was 8.5 cm; 75% were FNCLCC Grade 3. All patients underwent complete resection, including 15 patients (34%) who required re-excision to secure microscopic negative margins. Radiation therapy was given to 75% of patients, chemotherapy in 36%. At 5 years, OS was 75.3%; CCI of DSD, LR, and DM were 17.5%, 2.3%, and 32.5%. Larger tumor size was strongly associated with worse OS (p = 0.028) and DSD (p ≤ 0.001). A subgroup of patients (n = 10, 23%) with smaller, predominantly Grade 2 tumors underwent surgery alone without any LR or DM event at a median follow-up of 7.9 years. CONCLUSIONS: In PLPS, aggressive surgery and when appropriate, radiation therapy, results in excellent local control. Chemotherapy can be considered for larger tumors. Patients with smaller, Grade 2 tumors may be potentially cured with surgery alone.

Preoperative nutritional support to tackle morbidity in multivisceral resection for retroperitoneal sarcoma. Early outcomes from a novel nutritional prehabilitation program in a prospective cohort.

OBJECTIVE: Evaluate the feasibility and outcomes of the implementation of a routinely prehabilitation nutritional program (PNP) in retroperitoneal sarcoma (RPS) patients. SUMMARY BACKGROUND DATA: Rate of preoperative malnutrition is scarcely evaluated in RPS patients and the efficacy of a PNP in detecting and reverting malnutrition has not been studied. METHODS: Prospective study in a high-volume reference center for RPS; adult patients with primary or persistent RPS deemed surgically resectable were enrolled in a PNP. RESULTS: 119 patients underwent surgery for RPS at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, 73 (61.3 %) were enrolled in the PNP while the remaining served as control cohort. 43.8 % (32/73), 28.8 % (21/73), and 27.4 % (20/73) were classified as non-malnourished, moderately malnourished, and severely malnourished at diagnosis, respectively. Preoperative nutritional support was provided to 35 out of 73 patients (47.9 %). Among untreated patients 20 of 38 (52.6 %) experienced a preoperative worsening of their nutritional status, whereas among those in the prehabilitation program 16 of 35 (45.7 %) showed improvement. Surgical complications did not significantly differ between malnourished and non-malnourished patients, potentially due to increased use of diverting stomas in malnourished patients to prevent infectious complications. Reversal of initial malnutrition correlated with better postoperative outcomes, as evidenced by lower rates of severe complications (OR: 0.18, 95%CI 0.04-0.75, p = 0.02) and a lower Comprehensive Complication Index (OR: -0.28, 95%CI -0.51 to -0.06, p = 0.02) in multivariate analysis. CONCLUSIONS: The implementation of a prehabilitation nutritional program brought relevant benefits in terms of postoperative morbidity.

Extent of macroscopic vascular invasion predicts distant metastasis in primary leiomyosarcoma of the inferior vena cava.

BACKGROUND: In retroperitoneal leiomyosarcoma (RP LMS), the predominant issue is distant metastasis (DM). We sought to determine variables associated with this outcome and disease-specific death (DSD). METHODS: Data were retrospectively collected on patients with primary RP LMS treated at a high-volume center from 2002 to 2023. For inferior vena cava (IVC)-origin tumors, the extent of macroscopic vascular invasion was re-assessed on each resection specimen and correlated with preoperative cross-sectional imaging. Crude cumulative incidences were estimated for DM and DSD and univariable and multivariable models were performed. RESULTS: Among 157 study patients, median tumor size was 11.0 cm and 96.2% of cases were intermediate or high grade. All patients underwent complete resection, 56.7% received chemotherapy (43.9% neoadjuvant) and 14.6% received radiation therapy. Only tumor size and grade and not site of tumor origin (e.g., IVC vs. other) were associated with DM and DSD (p < 0.05). Among 64 patients with IVC-origin tumors, a novel 3-tier classification was devised based on the level of intimal disruption, which was associated with both DM (p = 0.007) and DSD (0.002). CONCLUSION: In primary RP LMS, only tumor size and grade are predictive of DM and DSD. In IVC-origin tumors, the extent of macroscopic vascular invasion is also strongly predictive of these outcomes.

Proteomic profiling improves prognostic risk stratification of the Sarculator nomogram in soft tissue sarcomas of the extremities and trunk wall.

BACKGROUND: High-risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by the Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline-based therapy compared to low/intermediate-risk patients. The biology underpinning these differential treatment outcomes remain unknown. METHODS: We analysed proteomic profiles and clinical outcomes of 123 eSTS patients. A Cox model for overall survival including the Sarculator was fitted to individual data to define four risk groups. A DNA replication protein signature-Sarcoma Proteomic Module 6 (SPM6) was evaluated for association with clinicopathological factors and risk groups. SPM6 was added as a covariate together with Sarculator in a multivariable Cox model to assess improvement in prognostic risk stratification. RESULTS: DNA replication and cell cycle proteins were upregulated in high-risk versus very low-risk patients. Evaluation of the functional effects of CRISPR-Cas9 gene knockdown of proteins enriched in high-risk patients using the cancer cell line encyclopaedia database identified candidate drug targets. SPM6 was significantly associated with tumour malignancy grade (p = 1.6e-06), histology (p = 1.4e-05) and risk groups (p = 2.6e-06). Cox model analysis showed that SPM6 substantially contributed to a better calibration of the Sarculator nomogram (Index of Prediction Accuracy = 0.109 for Sarculator alone versus 0.165 for Sarculator + SPM6). CONCLUSIONS: Risk stratification of patient with STS is defined by distinct biological pathways across a range of cancer hallmarks. Incorporation of SPM6 protein signature improves prognostic risk stratification of the Sarculator nomogram. This study highlights the utility of integrating protein signatures for the development of next-generation nomograms.

Surgical Outcome in Retroperitoneal Sarcoma Surgery: Accuracy of P-POSSUM, ACS-NSQIP, and Inflammatory Biomarkers Prognostic Index (IBPI) Risk-Calculators for Prediction of Severe and Overall Morbidity.

INTRODUCTION: Retroperitoneal sarcoma often requires comprehensive resection, leading to severe postoperative morbidity. The lack of disease-procedure specific tools for morbidity risk and the questionable accuracy of existing tools (ACS-NSQIP and P-POSSUM) in RPS surgery drove this study to assess these calculators' accuracy. METHODS: Retrospective analysis of primary RPS cases undergoing surgery at two sarcoma-referral centers was conducted. Predicted morbidity/mortality rates at 90 days postsurgery, classified by Clavien-Dindo (CD) and Comprehensive Complication Index (CCI), were compared with observed data. Accuracy was assessed by Brier Score and area under the curve (AUC). Inflammatory Biomarkers Prognostic Index (IBPI) also was tested. RESULTS: A total of 567 patients (median age 62 years; 53.6% male) with a median of four resected organs were included. 59% experienced surgical complications by 90 days postoperation, graded CD ≥ 3 in 30.5%, median CCI 20.9, with a mortality rate of 1.6% (8/567). Reoperation was required in 68 of 567 patients (12%). Thirty-day mortality was 1.1%. Severe complications occurred after 30th postoperative day in 3.5% cases. ACS-NSQIP predicted below-average complication for 65.1%, average for 16.9%, and above-average for 18% of patients. P-POSSUM predicted a 66% rate of morbidity and 4% mortality. None of the prediction tools were accurate, with Brier scores ranging 0.155-0.231 and no AUC ≥ 0.7. IBPI accuracy for predicting severe infective complication was low (AUC 0.58, Brier 0.161). CONCLUSIONS: The significant morbidity burden after MVR necessitates reliable evaluation, especially in frail patients. Given the limitations of ACS-NSQIP and P-POSSUM, a dedicated prediction tool for perioperative events in RPS candidates for MVR needs urgent development.

Opportunities and Challenges in Soft Tissue Sarcoma Risk Stratification in the Era of Personalised Medicine.

OPINION STATEMENT: Soft tissue sarcomas (STS) are a rare and heterogeneous group of cancers. Treatment options have changed little in the past thirty years, and the role of neoadjuvant chemotherapy is controversial. Accurate risk stratification is crucial in STS in order to facilitate clinical discussions around peri-operative treatment. Current risk stratification tools used in clinic, such as Sarculator, use clinicopathological characteristics and may be specific to anatomical site or to histology. More recently, risk stratification tools have been developed using molecular or immunological data. Combining Sarculator with other risk stratification tools may identify novel patient groups with differential clinical outcomes. There are several considerations when translating risk stratification tools into widespread clinical use, including establishing clinical utility, health economic value, being applicable to existing clinical pathways, having strong real-world performance, and being supported by investment into infrastructure. Future work may include incorporation of novel modalities and data integration techniques.

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

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.

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

OBJECTIVES: Spermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. METHODS: One hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. RESULTS: Over a median follow-up of 54 months (IQR 25-105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05). Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). CONCLUSION: Prompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

New Sarculator Prognostic Nomograms for Patients With Primary Retroperitoneal Sarcoma: Case Volume Does Matter.

OBJECTIVE: To update the current Sarculator retroperitoneal sarcoma (RPS) prognostic nomograms considering the improvement in patient prognosis and the case volume effect. BACKGROUND: Survival of patients with primary RPS has been increasing over time, and the volume-outcome relationship has been well recognized. Nevertheless, the specific impact on prognostic nomograms is unknown. METHODS: All consecutive adult patients with primary localized RPS treated at 8 European and North American sarcoma reference centers between 2010 and 2017 were included. Patients were divided into 2 groups: high-volume centers (HVC, ≥13 cases/year) and low-volume centers (LVC, <13 cases/year). Primary end points were overall survival (OS) and disease-free survival (DFS). Multivariable analyses for OS and DFS were performed. The nomograms were updated by recalibration. Nomograms performance was assessed in terms of discrimination (Harrell C index) and calibration (calibration plot). RESULTS: The HVC and LVC groups comprised 857 and 244 patients, respectively. The median annual primary RPS case volume (interquartile range) was 24.0 in HVC (15.0-41.3) and 9.0 in LVC (1.8-10.3). Five-year OS was 71.4% (95% CI: 68.3%-74.7%) in the HVC cohort and 63.3% (56.8%-70.5%) in the LVC cohort ( P =0.012). Case volume was associated with both OS (LVC vs. HVC hazard ratio 1.40, 95% CI: 1.08-1.82, P =0.011) and DFS (hazard ratio 1.93, 95% CI: 1.57-2.37, P <0.001) at multivariable analyses. When applied to the study cohorts, the Sarculator nomograms showed good discrimination (Harrell C index between 0.68 and 0.73). The recalibrated nomograms showed good calibration in the HVC group, whereas the original nomograms showed good calibration in the LVC group. CONCLUSIONS: New nomograms for patients with primary RPS treated with surgery at high-volume versus low-volume sarcoma reference centers are available in the Sarculator app.

Deciding individual treatment for primary retroperitoneal sarcoma.

INTRODUCTION: Retroperitoneal sarcomas (RPS) are rare mesenchymal tumors that account for only 0.1-0.2% of all malignancies. Management of this disease is challenging, and resection remains the cornerstone of treatment. Ongoing international collaboration has expanded our knowledge of this disease, allowing for a more personalized approach to RPS patients resulting in improved survival over time. Due to the heterogeneity of RPS, with differing recurrence patterns and sensitivities to neoadjuvant therapies based on histology and grade, management of RPS should be tailored to the individual patient. AREAS COVERED: Our review focuses on a histology-driven approach in the management of primary RPS. We searched relevant articles from 1993 to 2023 that investigated prognostic factors and treatment of patients with RPS and summarized recent advances and future directions in the field. EXPERT OPINION: Deeper understanding of the role of neoadjuvant radiotherapy and ongoing trials investigating the role of neoadjuvant chemotherapy will potentially contribute to the development of individualized treatment pathways.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

BACKGROUND: To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). METHODS: All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. RESULTS: Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p = .09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. CONCLUSION: In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

Six Surgical Stages in the Resection of Primary Right Retroperitoneal Liposarcoma: A Standardized Comprehensive Approach.

BACKGROUND: Surgery is the treatment mainstay in retroperitoneal sarcoma (RPS), a frontline comprehensive approach based on tumor removal en bloc with adherent viscera is mandatory especially for liposarcoma, where the normal retroperitoneal fat is undistinguishable from the well-differentiated tumor component.1-5 In this video, a reproducible and standardized six-stage approach to a primary right retroperitoneal liposarcoma is presented. PATIENT AND METHODS: A 23-cm right retroperitoneal, well-differentiated liposarcoma was diagnosed in a 68-year-old female patient in December 2021. The tumor involved the right kidney and adrenal gland; displacing anteriorly the right colon, the duodenum, and the pancreatic head; and invading part of the ipsilateral psoas muscle. After the publication of the STRASS trial and STREXIT results,6,7 neoadjuvant radiotherapy was delivered to a total dose of 50.4 Gy in 28 fractions with stable disease. Virtual 3D reconstruction of regional anatomy by Visible Patient was performed preoperatively. RESULTS: The patient underwent right retroperitoneal mass resection en bloc with ipsilateral kidney and adrenal gland, colon, psoas muscle, and portion of ipsilateral diaphragm. Of note, the resection of the psoas muscle was performed to obtain a safe posterior margin and accomplish a better clearance of fat of the posterior abdominal wall. This can be limited to the psoas fascia whenever the tumor is not adherent to it. A six-stage approach was performed, as described in the supplementary video file. CONCLUSIONS: RPS resection is complex and requires a broad range of surgical expertise. A staged approach that can be followed in virtually all cases is highly recommended to achieve an optimal tumor resection.

Long-term survivors with desmoplastic small round cell tumor (DSRCT): Results from a retrospective single-institution case series analysis.

OBJECTIVE: To report on a retrospective study of primary DSRCT aiming at characterizing long-term survivors (LTS). METHODS: All consecutive patients treated at our institution for a primary DSRCT between 2000 and 2021 were retrospectively identified. Patients received multiagent chemotherapy ± surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) ± whole abdomino-pelvic radiotherapy (WAP-RT) ± high-dose chemotherapy ± maintenance chemotherapy (MC). Event-free survival (EFS) and overall survival (OS) were estimated by Kaplan-Meier method. Patients alive, without evidence of disease at ≥36 months from diagnosis, were defined as LTS. RESULTS: Thirty-eight patients were identified. All received multiagent chemotherapy; 27/38 (71%) surgery (7/27 [26%] plus HIPEC), 9/38 (24%) WAP-RT, 12/38 (32%) MC. At a median-follow-up of 37 months (IQR 18-63), overall median-EFS and median-OS were 15 and 37 months, respectively. All events occurred within 35 months. In patients who underwent surgery, median-EFS and median-OS were 19 and 37 months (23 and 43 months after R0/R1, and 10 and 19 months after R2 resection), respectively. LTS were 5/38 (13%), alive at 37, 39, 53, 64, 209 months. None had liver or extra-abdominal metastasis at diagnosis, they all received R0/R1 resection, 3/5 had WAP-RT, 2/5 MC, 1/5 received high-dose chemotherapy, none HIPEC. CONCLUSIONS: In our series cure was likely achieved in 13% of DSRCT. LTS had no liver/extra-abdominal disease, were treated with complete surgery, and possibly WAP-RT/MC.

Organ Infiltration and Patient Risk After Multivisceral Surgery for Primary Retroperitoneal Liposarcomas.

BACKGROUND: The extent of histological organ involvement (HOI) to organs and structures of a retroperitoneal liposarcoma may have prognostic implications. This study investigated incidence, characteristics, and risk association of HOI in these patients. PATIENTS AND METHODS: Data of patients who underwent multivisceral resection for primary liposarcoma (2009-2014) were retrospectively analyzed. HOI was the variable of interest and was classified into four degrees: absent (HOI-0), perivisceral (HOI-1), initial (HOI-2), and advanced (HOI-3). Primary endpoint was overall survival (OS). Secondary endpoint was disease-free survival (DFS). The prognostic value of HOI was adjusted for preoperative treatment and the Sarculator nomogram score. RESULTS: A total of 109 patients were included. HOI-0, HOI-1, HOI-2, and HOI-3 were detected in 9 (8.3%), 11 (10.1%), 43 (39.4%), and 46 (42.2%) patients. Median follow-up was 8.4 years [interquartile range (IQR) 7.2-9.6 years]. There were 68 recurrences and 50 patient deaths observed, resulting in a 10-year OS and DFS of 51.1% [95% confidence interval (CI) 41.9-62.1%] and 34.1% (95% CI 25.2-46.1%), respectively. Clinically relevant HOIs (HOI-2 and HOI-3) were found in 35/45 (77.8%) and 54/64 (84.4%) cases of well- and de-differentiated liposarcomas, respectively. On multivariable survival analysis, patients with HOI-3 had significantly shorter OS (HOI-3 vs HOI-0/HOI-1 HR 2.92; p = 0.012) and DFS (HOI-3 vs HOI-0/HOI-1 HR 2.23; p = 0.045), independently of the nomogram score (OS: HR 2.93; p < 0.001; DFS: HR 1.78; p = 0.003). CONCLUSIONS: Initial and advanced HOIs are frequently detected in both well-differentiated and de-differentiated liposarcomas, supporting that multivisceral resection may be needed. HOI stratifies the risk of patients with primary retroperitoneal liposarcoma.

Preoperative Neutrophil-to-Lymphocyte Ratio and a New Inflammatory Biomarkers Prognostic Index for Primary Retroperitoneal Sarcomas: Retrospective Monocentric Study.

PURPOSE: Inflammatory biomarkers and neutrophil-to-lymphocyte ratio (NLR) are associated with prognosis in several tumors. Data on sarcomas are limited, and insufficient on retroperitoneal sarcoma (RPS). EXPERIMENTAL DESIGN: Patients with primary RPS operated between 2002 and 2016 were included. Hemoglobin, monocytes, NLR, platelet-to-lymphocyte ratio (PLR) were retrieved and analyzed both individually and combined into a prognostic index (IBPI). Correlation with clinicopathologic variables was studied, as well as postoperative morbidity according to NLR and IBPI risk categories. The association between overall survival (OS) and biomarkers and, in addition, the 7-year Sarculator-predicted OS probability (pOS) was analyzed using univariable and multivariable Cox models. RESULTS: 423/463 patients had complete data. The median follow-up was 84 months. The median NLR was 3.3 (IQR, 2.4-4.7), with significant variation across histologies. NLR was the only biomarker that independently predicted OS (HR, 1.2; 95% CI, 1.03-1.40; P = 0.02). The IBPI showed good discrimination for subgroups at different OS (log-rank test P < 0.0001). The Cox model for pOS alone showed a 7-year index of prediction accuracy of 26.9, which increased to 29.5 when IBPI was added to pOS as a complementary prognostic tool. IBPI was also associated with the risk of serious infectious postoperative complications (P = 0.0094; noninfectious complications, P = 0.6463). CONCLUSIONS: NLR was an independent prognostic factor for OS in RPS. When combined into a prognostic index with hemoglobin, monocytes, and PLR, it serves as a readily available prognostic tool addressing tumor-related inflammation and helps in classifying RPS risk in addition to the Sarculator nomogram.