Safety and efficacy of percutaneous image-guided ablation for soft tissue sarcoma metastases to the liver.

PURPOSE: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver. MATERIALS AND METHODS: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival. RESULTS: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1-8), whereas the median size of metastases were 1.8 cm (0.3-8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver-specific progression-free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy-free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology-agnostic outcomes (2 years, 89% vs 82%, p = .35). CONCLUSION: Percutaneous image-guided liver ablation of soft tissue sarcoma metastases is safe and efficacious.

Phase 1b study of combined selinexor and eribulin for the treatment of advanced solid tumors and triple-negative breast cancer.

BACKGROUND: Selinexor (KPT-330) is a potent inhibitor of exportin 1 (XPO1), in turn inhibiting tumor growth. Selinexor enhances the antitumor efficacy of eribulin in triple-negative breast cancer (TNBC) in vitro and in vivo. Given the unmet medical need in TNBC and sarcoma, the authors explored the safety and efficacy of this combination. METHODS: The authors conducted a phase 1b trial of combined selinexor and eribulin using a 3 + 3 dose-escalation design in patients who had advanced solid tumors and in those who had TNBC in a dose-expansion cohort. RESULTS: Patients with TNBC (N = 19), sarcoma (N = 9), and other cancers (N = 3) were enrolled in the dose-escalation cohort (N = 10) and in the dose-expansion cohort (N = 21). The median number lines of prior therapy received was four (range, from one to seven prior lines). The most common treatment-related adverse events for selinexor were nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%). One dose-limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia. The recommended phase 2 dose was 80 mg of selinexor orally once per week and 1 mg/m2 eribulin on days 1 and 8 intravenously every 3 weeks. The objective response rate (ORR) was 10% in three patients. In the dose-escalation cohort, the ORR was 10%, whereas six patients with had stable disease. In the TNBC dose-expansion cohort (n = 18), ORR was 11%, and there were two confirmed partial responses with durations of 10.8 and 19.1 months (ongoing). CONCLUSIONS: Selinexor and eribulin had an acceptable toxicity profile and modest overall efficacy with durable responses in select patients. PLAIN LANGUAGE SUMMARY: Effective therapies for advanced, triple-negative breast cancer and sarcoma represent an unmet need. Exportin 1 is associated with the transport of cancer-related proteins. Preclinical studies have demonstrated tumor growth inhibition and enhanced tumor sensitivity in patients who receive selinexor combined with eribulin. In this phase 1b study, the authors evaluated the safety profile and clinical activity of the combination of selinexor, a potent oral inhibitor of exportin 1, and eribulin in patients with advanced cancers enriched for triple-negative breast cancer or sarcoma. The combination was well tolerated; most adverse events were mild or moderate, reversible, and managed with dose modifications or growth factor support. The combination of selinexor and eribulin produced an antitumor response, particularly in some patients with triple-negative breast cancer. This work lays the foundation for prospective investigations of the role of selinexor and eribulin in the treatment of triple-negative breast cancer.

Myxoid Liposarcomas: Systemic Treatment Options.

OPINION STATEMENT: Myxoid/round-cell liposarcoma (MRCL) account for 30% of liposarcomas and are the most chemo-sensitive subtype of liposarcoma. The 5-year local relapse and distant metastasis rates are 10% and 20%, respectively. In the advanced setting, the first-line median progression-free survival and overall survival is 9 and 30 months, respectively. The overall response rate (ORR) by RECIST with anthracycline-based chemotherapy is around 40% and with trabectedin is 20%, although response is higher when captured by CHOI criteria. Anthracycline-based combination chemotherapy regimens remain the standard of care first-line treatment option. However, trabectedin is also effective and may be considered in the first-line setting when anthracyclines cannot be prescribed. Beyond chemotherapy, new therapeutic classes are being developed, including autologous adoptive modified T cell receptor cellular therapies which have shown promising results thus far. These new therapies utilize the immunogenic potential of cancer testis antigens, NY-ESO-1 and MAGE-A4, which are expressed in the vast majority of MRCL. Early phase trials have shown encouraging results with up to 40% ORR and a median progression-free survival up to 8.7 months. Other innovative strategies are being developed, tailored to the molecular biology of MRCL. This review summarizes current evidence for the use of standard chemotherapy and the new biomarker-selected treatments under development.

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute.

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial.

BACKGROUND: Few standard treatment options are available for patients with metastatic sarcomas. We did this trial to evaluate the efficacy, safety, and changes in the tumour microenvironment for durvalumab, an anti-PD-L1 drug, and tremelimumab, an anti-CTLA-4 drug, across multiple sarcoma subtypes. METHODS: In this single-centre phase 2 trial, done at The University of Texas MD Anderson Cancer Center (Houston, TX USA), patients aged 18 years or older with advanced or metastatic sarcoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least one previous line of systemic therapy were enrolled in disease subtype-specific groups (liposarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, alveolar soft-part sarcoma, chordoma, and other sarcomas). Patients received 1500 mg intravenous durvalumab and 75 mg intravenous tremelimumab for four cycles, followed by durvalumab alone every 4 weeks for up to 12 months. The primary endpoint was progression-free survival at 12 weeks in the intention-to-treat population (all patients who received at least one dose of treatment). Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02815995, and is completed. FINDINGS: Between Aug 17, 2016, and April 9, 2018, 62 patients were enrolled, of whom 57 (92%) received treatment and were included in the intention-to-treat population. With a median follow-up of 37·2 months (IQR 1·8-10·1), progression-free survival at 12 weeks was 49% (95% CI 36-61). 21 grade 3-4 treatment-related adverse events were reported, the most common of which were increased lipase (four [7%] of 57 patients), colitis (three [5%] patients), and pneumonitis (three [5%] patients). Nine (16%) patients had a treatment related serious adverse event. One patient had grade 5 pneumonitis and colitis. INTERPRETATION: The combination of durvalumab and tremelimumab is an active treatment regimen for advanced or metastatic sarcoma and merits evaluation in specific subsets in future trials. FUNDING: AstraZeneca.

Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center.

Palbociclib has been evaluated in early phase trials for well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) patients, with reported median progression-free survival (PFS) of 18 weeks. Here, we report on real-world use and surgical outcomes associated with palbociclib treatment. We retrospectively reviewed 61 consecutive patients with retroperitoneal WDLPS (n = 14) or DDLPS (n = 47) treated with palbociclib monotherapy between 1 March 2016 and 28 February 2021 at The University of Texas MD Anderson Cancer Center. At palbociclib initiation, median age was 64 (interquartile range [IQR] 56-72). In WDLPS and DDLPS cohorts, the median number of prior systemic treatments was 0 (IQR 0-0) and 2 (IQR 0-4), respectively. Median number of prior surgeries was 2 (WDLPS IQR 1-2.75) and 2 (DDLPS IQR 1-3). Median PFS was 9.2 (WDLPS IQR 3.9-21.9) and 2.6 months (DDLPS IQR 2.0-6.1), with median time on treatment of 7.4 months (WDLPS IQR 3.5-14.2) and 2.7 months (DDLPS IQR 2.0-5.7). Twelve patients ultimately underwent surgical resection. Resections were macroscopically complete (R0/R1) in half (n = 6/12), among whom only one patient experienced relapse after resection (median follow-up 7.5 months). All patients who underwent macroscopically incomplete resections progressed after surgery with median time to progression of 3.3 months (IQR 2.3-4.4). Surgery after palbociclib treatment was not associated with improved overall survival. Efficacy of palbociclib monotherapy for patients with advanced WDLPS and DDLPS is disappointing. While palbociclib may have been used to delay surgery, there was no clear benefit from treatment and few patients achieved prolonged tumor control.

OER-073: A multicenter phase 2 study evaluating the role of pazopanib in angiosarcoma.

BACKGROUND: Angiosarcomas are rare mesenchymal sarcomas that can present as primary cutaneous or noncutaneous disease. They express a variety of vascular endothelial growth factor receptors. The authors hypothesized that the treatment of angiosarcoma with pazopanib, a multikinase inhibitor with activity against vascular endothelial growth factor receptors, would result in disease response and prolonged disease stabilization. METHODS: This was an open-label, phase 2 trial of pazopanib in patients who had incurable angiosarcoma. The co-primary end points were response according to the Response Evaluation Criteria in Solid Tumors and progression-free survival (PFS) at 3 months. The starting dose of pazopanib was 800 mg daily. RESULTS: Twenty-nine patients were accrued between 2011 and 2018, and 22 patients were evaluable for response. Toxicities were similar to those identified in prior reports. There was one partial response (3%), and the clinical benefit rate (including complete responses, partial responses, and stable disease) was 48%, which was observed more frequently in patients who had cutaneous disease. The median PFS was 14.4 weeks, and the 3-month PFS rate determined by Kaplan-Meier estimate was 54.6% (95% CI, 36.0%-82.9%), meeting the primary study objective. The Kaplan-Meier overall survival estimate was 16.1 months. CONCLUSIONS: Pazopanib therapy in patients who had incurable angiosarcoma was associated with meaningful disease control, especially in those who had cutaneous disease with limited objective responses. LAY SUMMARY: Angiosarcoma is a rare cancer that can be found on the skin or in internal organs. This study tested pazopanib, an oral targeted medication, to determine its benefit in patients with angiosarcoma who could not undergo the removal of their tumors by surgery. Pazopanib treatment was safe, and no new side effects were reported. The study showed that pazopanib controlled tumor growth in one half of patients at 3 months and was more common in angiosarcomas of the skin; it led to tumor shrinkage in a minority of patients (1 of 29).

Clinical activity of checkpoint inhibitors in angiosarcoma: A retrospective cohort study.

BACKGROUND: Systemic treatments for angiosarcoma remains an area of unmet clinical need. The authors conducted this retrospective study to assess the clinical activity of checkpoint inhibitors in patients with angiosarcoma. The primary objective was to assess the objective response rate, and the secondary objective was to assess the progression-free and overall survival durations and disease control rate. METHODS: Patient data were obtained using The University of Texas MD Anderson Cancer Center Tumor Registry database. The final study population was refined to only include patients who had undergone pembrolizumab monotherapy. The objective response rate was evaluated using RECIST/irRECIST version 1.1. Progression-free survival and overall survival were defined as the time from the initiation of immunotherapy to disease progression or recurrence, death, or last follow-up and to death or last follow-up, respectively. RESULTS: The final cohort comprised 25 patients. Most patients had metastatic disease (72%) and had undergone at least two lines of systemic therapy (80%) before starting pembrolizumab. The objective response rate was 18%, whereas the disease control rate was 59%. The median progression-free survival duration was 6.2 months and was not significantly different between the cutaneous (4.7 months) and visceral angiosarcoma (6.2 months) groups (p = .42). The median overall survival duration was 72.6 months. Toxicities were recorded for eight patients, with fatigue, anemia, constipation, and rash being the most common. CONCLUSIONS: Pembrolizumab shows durable clinical activity in angiosarcoma. These findings suggest that checkpoint inhibition as monotherapy or combination therapy is likely to have a high probability of success.© 2022 American Cancer Society. LAY SUMMARY: This is the largest retrospective study to assess the clinical activity of checkpoint inhibitor monotherapy in angiosarcomas. The study includes an adequate number of patients with visceral angiosarcoma that enabled to obtain meaningful clinical insights that were previously unavailable. Our findings indicate an improvement in progression-free survival with pembrolizumab that is comparable to other active agents in angiosarcoma. Pembrolizumab monotherapy in angiosarcomas also has a favorable tolerability profile. Our findings emphasize the need for prospective studies to evaluate the activity of pembrolizumab monotherapy and combination therapy.

A randomized, open-label, phase 2, multicenter trial of gemcitabine with pazopanib or gemcitabine with docetaxel in patients with advanced soft-tissue sarcoma.

BACKGROUND: Therapeutic options for patients with advanced soft-tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. METHODS: The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline-based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m2 on days 1 and 8 and docetaxel at a dose of 100 mg/m2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression-free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent-to-treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). RESULTS: A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log-rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). CONCLUSIONS: The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.

Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study.

BACKGROUND: Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumors (GISTs) as at least fourth-line therapy. In INVICTUS, ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.d. was allowed after progressive disease (PD) on 150 mg QD by blinded independent central review using modified RECIST 1.1. We report the efficacy and safety of ripretinib IPDE to 150 mg b.i.d. after PD among patients randomized to ripretinib 150 mg QD in the INVICTUS study. MATERIALS AND METHODS: Tumor imaging was performed every 28-day cycle for the first four cycles in the ripretinib 150 mg QD period and then every other cycle, including the 150 mg b.i.d. PERIOD: Among the ripretinib IPDE patients, progression-free survival (PFS)1 was the time from randomization until PD; PFS2 was the time from the first dose of ripretinib 150 mg b.i.d. to PD or death. RESULTS: Among 43 ripretinib IPDE patients, median PFS1 was 4.6 months (95% confidence interval [CI], 2.7-6.4) and median PFS2 was 3.7 months (95% CI, 3.1-5.3). Median overall survival was 18.4 months (95% CI, 14.5-not estimable). Ripretinib 150 mg b.i.d. (median duration of treatment 3.7 months) was well tolerated with new or worsening grade 3-4 treatment-emergent adverse events (TEAEs) of anemia in six (14%) and abdominal pain in three (7%) patients. Ripretinib 150 mg b.i.d. was discontinued because of TEAEs in seven (16%) patients. CONCLUSION: Ripretinib 150 mg b.i.d. after PD on 150 mg QD may provide additional clinically meaningful benefit with an acceptable safety profile in patients with at least fourth-line GISTs. IMPLICATIONS FOR PRACTICE: Of the 85 patients with advanced gastrointestinal stromal tumor having received at least three prior anticancer therapies randomized to ripretinib 150 mg once daily (QD) in the phase III INVICTUS study, 43 underwent ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.d. after progressive disease (PD). Median progression-free survival was 4.6 months before and 3.7 months after ripretinib IPDE. The safety profile of ripretinib 150 mg b.i.d. was acceptable. These findings indicate ripretinib IPDE to 150 mg b.i.d. may provide additional clinical benefit in patients with PD on ripretinib 150 mg QD, for whom limited treatment options exist.

Outcomes of systemic therapy in metastatic phyllodes tumor of the breast.

PURPOSE: Metastatic phyllodes tumors of the breast (MPT) are rare breast neoplasms, limiting development of standardized treatment approaches. We sought to characterize the largest group of MPT thus far reported, evaluating systemic therapy outcomes. METHODS: Adult patients diagnosed with MPT between 1993 and 2015 and followed at MD Anderson Cancer Center were selected for retrospective chart review. Systemic therapy was sorted into: adriamycin/ifosfamide (AI), other anthracycline regimens, other ifosfamide regimens, gemcitabine-based regimens, and other. Given one patient may have received more than one regimen, we assumed that the effects of each regimen were independent from previous therapy. Median overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Log-rank test was performed to evaluate the difference in OS between patient characteristics groups, and the differences in PFS between the five chemotherapy regimens. RESULTS: We identified 50 MPT patients, with 31 patients receiving 61 systemic regimens. Median OS was 10.7 months (95% CI: 8.67, 16.5). AI had a PFS of 9.10 months (95% CI: 5.03, 14.2), other ifosfamide regimens had a PFS of 5.10 months (95% CI: 0.67, 12.1), other anthracycline regimens had a PFS of 3.65 months (95% CI: 1.17, 7.90), gemcitabine-based regimens had a PFS of 2.80 months (95% CI: 1.83, 4.60), and other regimens had a PFS of 1.67 months (95% CI: 1.13, 7.77). CONCLUSION: MPT patients are a unique population with limited characterization to date. Our study demonstrates activity of multiple sarcoma-directed chemotherapy regimens, with ifosfamide-containing regimens having the longest PFS.

National Utilization of Imatinib in the Management of Resected Gastrointestinal Stromal Tumors.

BACKGROUND: Imatinib decreases recurrence risk and improves overall survival (OS) in localized gastrointestinal stromal tumors (GISTs); however, the extent to which patients receive appropriate treatment in the US has not been well characterized. METHODS: Patients with non-metastatic, resectable GIST were included in this study (National Cancer Database, 2010-2015). Those with a low-risk of recurrence were classified as receiving overtreatment or guideline-concordant treatment, while those with a high-risk of recurrence were classified as receiving undertreatment or guideline-concordant treatment. Multivariable logistic regression was used to determine factors associated with non-concordant treatment. The association between non-concordant treatment and OS was evaluated using multivariable Cox regression and propensity score matching. RESULTS: Among 3088 patients with high-risk GIST, 41% were undertreated, and among 3908 patients with low-risk GIST, 18.8% were overtreated. For patients with high-risk GIST, age > 60 years, African American race, and treatment at a community or comprehensive cancer program were associated with undertreatment. Among low-risk patients, small bowel primary, tumor size > 2 cm, and tumors with > 1 mitotic figure per 50 high-power fields were more likely to be overtreated. After propensity score matching, guideline-concordant therapy was associated with an 8.8% improvement in 5-year OS (81.9% vs. 73.1%, p = 0.002) for those with high-risk GIST and decreased risk of death (hazard ratio 0.63, 95% confidence interval 0.47-0.84). There was no statistically significant difference in survival for patients with low-risk GIST with the addition of imatinib overtreatment (overtreatment 93.9% vs. 89.6%, p = 0.053). CONCLUSIONS: Nearly 30% of GIST patients do not receive guideline-concordant treatment and future work is needed to understand the factors driving non-concordant treatment.

Evaluating the Impact of Surveillance Follow-Up Intervals in Patients Following Resection of Primary Well-Differentiated Liposarcoma of the Retroperitoneum.

BACKGROUND: Resection of recurrent retroperitoneal well-differentiated liposarcoma (RP-WDLPS) is unlikely to result in cure. Thus, most clinicians delay surgery after recurrence until symptom intolerance or increasing rate of disease progression. The aim of this study was to determine whether longer surveillance intervals in this population would impact outcomes or delay treatment in those who recur. METHODS: A retrospective review of patients with primary RP-WDLPS who underwent resection between April 1996 and April 2017 and surveillance at MDACC (n = 91) was performed. RESULTS: Median age at diagnosis of primary RP-WDLPS was 61 years; median tumor size was 30 cm. Complete resection was achieved in 85 (93.4%) patients. Among patients who underwent complete resection, recurrence occurred in 53 (60.2%) with median time to recurrence of 27.0 months. Thirty-six (69.6%) of these patients underwent resection of recurrent disease at a median 40.2 months from primary tumor resection. Surveillance imaging at 4-month (vs 3-month) intervals would not have impacted recurrence management in 84 (95.5%) patients; imaging at 6-month (vs 3-month) intervals would not have impacted management of recurrence in 80 (90.9%). CONCLUSIONS: Recurrence was common, often occurring beyond the early postoperative period following primary RP-WDLPS resection. More frequent surveillance imaging (q3-4 vs q6 months) in the first 2 years following primary RP-WDLPS resection may not significantly impact timing of surgery or systemic therapy for recurrence. If longer surveillance intervals were shown to be safe with equivalent outcomes in prospective studies, the resulting change in practice could lead to decreased anxiety and cost for patients and healthcare systems.

Ripretinib for advanced gastrointestinal stromal tumor: Plain language summary of the INVICTUS study.

The purpose of this summary is to help you understand the results of the INVICTUS study originally published in the journal Lancet Oncology. INVICTUS is a clinical study which looked at ripretinib as a potential treatment for advanced gastrointestinal stromal tumor, also known as GIST. GIST is a type of cancer that starts in the digestive tract, also known as the gastrointestinal tract. In the study, all participants had advanced GIST and needed a fourth-line (or greater) treatment following the failures of three previous treatments. The study looked at how well ripretinib worked compared with a nonactive medicine (known as a placebo) and at the side effects. Participants were given ripretinib at a dose of 150 mg once a day or a placebo. The results of the INVICTUS study showed ripretinib increased the length of time participants survived before their cancer got worse. Treatment with ripretinib was associated with side effects that varied in severity. The results of this study led to ripretinib, also known by the brand name Qinlock®, being approved in the USA by regulators as the only medication for adults with advanced GIST who have previously been treated with 3 or more types of treatment called tyrosine kinase inhibitors. ClinicalTrials.gov NCT number: NCT03353753.

Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma.

Objective: Compare health-related quality of life (HRQoL) of selinexor versus placebo in patients with dedifferentiated liposarcoma. Materials & methods: HRQoL was assessed at baseline and day 1 of each cycle using the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire. Results were reported from baseline to day 169 (where exposure to treatment was maximized while maintaining adequate sample size). Results: Pain scores worsened for placebo versus selinexor across all postbaseline visits, although differences in HRQoL at some visits were not significant. Other domains did not exhibit significant differences between arms; however, scores in both arms deteriorated over time. Conclusion: Patients treated with selinexor reported lower rates and slower worsening of pain compared with patients who received placebo.

Lay abstract The goal of this study was to compare the health-related quality of life (HRQoL) of patients with advanced unresectable dedifferentiated liposarcoma treated with selinexor compared with those treated with placebo. HRQoL was measured prior to treatment initiation and at the first day of each cycle of their treatment using the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire. Pain scores worsened for placebo compared with selinexor across all visits after treatment, but differences at some visits were not significant. Other domains did not exhibit significant differences between arms; however, scores in both arms worsened over time reflecting the progressive disease burden in this patient population. As pain is one of the most devastating symptoms associated with advanced and progressing cancers, the significant reduction in pain in the selinexor arm, according to patient perception, represent a relevant added value of this drug in dedifferentiated liposarcoma.

The degree of sclerosis is associated with prognosis in well-differentiated liposarcoma of the retroperitoneum.

BACKGROUND AND OBJECTIVES: Well-differentiated liposarcomas (WDL) are often partly composed of sclerotic tissue, however, the amount varies widely between tumors, and its prognostic significance is unknown. We hypothesized that tumors with more sclerosis would behave more aggressively. METHODS: Primary retroperitoneal WDL from 29 patients resected at our institution with follow-up were histologically evaluated by soft tissue pathologists blinded to outcome. Tumors with ≥ 10% sclerosis were designated "sclerotic" while tumors with < 10% sclerosis were designated as "minimally sclerotic". Cellular and dedifferentiated tumors were excluded. Clinical parameters and radiologic assessments on computed tomography (CT) were recorded. RESULTS: Histological evaluation identified 13 minimally sclerotic WDL and 16 sclerotic WDL. Median follow-up was 9 years (range, 3-20). Median recurrence-free survival (RFS) and median overall survival (OS) were 6.16 and 13.9 years, respectively. Compared with patients with sclerotic WDL, those with minimally sclerotic WDL had superior RFS (HR = 0.17 [95% CI, 0.06-0.53], P = .002) and OS (log-rank test, P = .002). Sclerotic WDL exhibited higher Houndsfield Units than minimally sclerotic WDL (26 vs 1, P = .040). CONCLUSIONS: Minimally sclerotic WDL were associated with more favorable outcome compared with sclerotic tumors. Assessment of sclerosis in WDL is likely a useful prognostic marker.

Olaratumab in the management of advanced soft tissue sarcoma.

Olaratumab, the first-in-class anti-PDGFRα monoclonal antibody, has been contingently approved in combination with doxorubicin to treat adult patients with advanced soft tissue sarcoma for improving progression-free and overall survival. Olaratumab-doxorubicin combination has tolerable safety profile, which mimics that of doxorubicin monotherapy, with the exception of infusion-related reactions. Survival data of an ongoing confirmatory phase 3 trial are forthcoming to ascertain the optimal role of this product in the management algorithm of advanced soft tissue sarcoma. Active research is ongoing to identify biomarkers predictive of clinical benefit to olaratumab, to expand its utility to the pediatric population, and to explore its safety and efficacy in combination with other active regimens.

Activity of Pazopanib and Trabectedin in Advanced Alveolar Soft Part Sarcoma.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan disease, without active drugs approved in the front line. Pazopanib and trabectedin are licensed for sarcoma treatment from second-line, but very little and contradictory data are available on their activity in ASPS. Lacking ongoing and/or planned clinical trials, we conducted a multi-institutional study involving the reference sites for sarcoma in Europe, U.S., and Japan, within the World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin. MATERIALS AND METHODS: From May 2007, 14 of the 27 centers that were asked to retrospectively review their databases had identified 44 advanced ASPS patients treated with pazopanib and/or trabectedin. Response was evaluated by Response Evaluation Criteria in Solid Tumors 1.1. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. RESULTS: Among 30 patients who received pazopanib, 18 were pretreated (13 with other antiangiogenics). Response was evaluable in 29/30 patients. Best responses were 1 complete response, 7 partial response (PR), 17 stable disease (SD), and 4 progressions. At a 19-month median follow-up, median PFS was 13.6 months (range: 1.6-32.2+), with 59% of patients progression-free at 1 year. Median OS was not reached.Among 23 patients treated with trabectedin, all were pretreated and evaluable for response. Best responses were 1 PR, 13 SD, and 9 progressions. At a 27-month median follow-up, median PFS was 3.7 months (range: 0.7-109), with 13% of patients progression-free at 1 year. Median OS was 9.1 months. CONCLUSION: The value of pazopanib in advanced ASPS is confirmed, with durable responses, whereas the value of trabectedin appears limited. These results are relevant to defining the best approach to advanced ASPS. IMPLICATIONS FOR PRACTICE: This retrospective study, conducted among the world reference centers for treatment of sarcoma, confirms the value of pazopanib in patients with advanced alveolar soft part sarcoma (ASPS), with dimensional and durable responses, whereas trabectedin shows a limited activity. Alveolar soft part sarcoma is resistant to conventional cytotoxic chemotherapy. Pazopanib and trabectedin are licensed for treatment of sarcoma from second line; in the lack of prospective clinical trials, these results are relevant to defining ASPS best management and strongly support initiatives aimed at obtaining the approval of pazopanib in the front line of the disease.

Salvage Surgery for Recurrent Retroperitoneal Well-Differentiated Liposarcoma: Early Reoperation may not Provide Benefit.

PURPOSE: Current evidence regarding salvage resection for recurrent retroperitoneal (RP) sarcomas generally lacks detailed histology-specific analyses, but the aggressiveness of these tumors varies widely by histology. We investigated associations between timing and extent of salvage surgery and survival outcomes in patients with recurrent RP well-differentiated liposarcoma (WDLPS). METHODS: The University of Texas MD Anderson Cancer Center Surgical Oncology sarcoma database was reviewed to identify patients with RP WDLPS who underwent surgical resection for first recurrent disease (salvage surgery) in 1995-2015. Medical records were retrospectively reviewed to identify factors associated with overall survival and disease-free survival. RESULTS: We identified 52 patients who underwent salvage surgery for RP WDLPS for first local recurrence; 28 (54%) underwent salvage surgery within 6 months after recurrence. Concomitant organ resections were performed in 32 (62%) patients, 4 (13%) of whom had pathologic invasion of resected organs. After R0/R1 resections (n = 45), 38 (84%) experienced a second local recurrence. Multivariable analyses revealed that organ invasion at the primary surgery [hazard ratio (HR) 13.08; p = 0.005] and disease-free interval < 1 year (HR 3.64; p = 0.044) were associated with shorter overall survival. Recurrence-to-salvage interval < 6 months was associated with shorter disease-free survival (HR 2.18; p = 0.025). Concomitant organ resection was associated with a longer hospital stay: ≥ 14 days (odds ratio 21.58; p = 0.007). CONCLUSIONS: Early salvage surgery may not always be the best approach for recurrent RP WDLPS patients. Because organ invasion is rare among recurrent RP WDLPS patients and concomitant organ resection is associated with a longer hospital stay, preservation of uninvolved organs should be considered.

Long-Term Survival According to Histology and Radiologic Response to Preoperative Chemotherapy in 126 Patients Undergoing Resection of Non-GIST Sarcoma Liver Metastases.

BACKGROUND: Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM. PATIENTS AND METHOD: Patients who underwent liver resection for NGSLM during 1998-2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model. RESULTS: 126 patients [62 (49%) with leiomyosarcoma] were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (p = 0.04), but radiologic response according to RECIST 1.1 criteria was not. CONCLUSIONS: Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.