Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry

Alveolar soft-part sarcoma; Immune checkpoint; ImmunotherapySarcoma alveolar de partes blandas; Puntos de control inmunológico; InmunoterapiaSarcoma alveolar de parts toves; Punts de control immunològic; ImmunoteràpiaBackground Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. Materials and methods Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. Results Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. Conclusions This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.DSM is a recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155). The authors thank SELNET project. SELNET has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 825806

MRI T2 mapping assessment of T2 relaxation time in desmoid tumors as a quantitative imaging biomarker of tumor response: preliminary results

ObjectivesBecause size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity.MethodsThis IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters.ResultsMedian patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12).ConclusionsAnalysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability

Adjuvant Therapies in Metastatic Bone Disease

Bone is a common site of metastatic disease in both solid tumor and hematologic malignancies. Skeletal involvement of cancer and the complications from these metastases can produce significant morbidity including, but not limited to, pathologic fractures and pain, hypercalcemia, and spinal cord or nerve root compression with neurologic compromise. Modern therapeutic advances have been developed towards the preservation of independence and improvement in quality of life, specifically with loss of mobility and social functioning in patients with metastatic bone disease. As such, the management of bone metastases is often complex, requiring an interdisciplinary and multimodal approach among surgeons, radiation oncologists, and medical oncologists. The aim of this discussion is to highlight the current recommendations regarding adjuvant treatments – local and systemic – in metastatic bone disease, including both radiotherapy and pharmaceutical interventions

Life after breast, prostate, and colon cancer: Primary care's role

When patients survive cancer, they eventually come back to their primary care physicians. This group has special needs, including surveillance for recurrent and new cancer, health promotion, and interventions to mitigate the lingering effects of the cancer and the adverse effects of its treatment

Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients

Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. The genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating tumor DNA (ctDNA) offers a rapid and noninvasive method of next-generation sequencing (NGS) that could be used for diagnosis, therapy, and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes using NGS. Results: Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. Forty-five (76%) were female with a median age of 63 (range, 38–87) years. All samples were designated metastatic. The most common alterations were detected in Tp53 (65%), BRAF (13%), CCNE (13%), EGFR (12%), PIK3CA (12%), FGFR1 (10%), RB1(10%), KIT (8%), and PDGFRA (8%). Some of the other alterations included RAF1, ERBB2, MET, PTEN TERT, APC, and NOTCH1. Potentially targetable mutations, by Food and Drug Administration–approved or clinical trials, were found in 24 (40%) of the 73 patients. Four patients (5%) were found to have incidental germline TP53 mutations. Conclusion: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of current targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma

Radiologic screening and surveillance in hereditary cancers

Hereditary cancer syndromes comprise an important subset of cancers caused by pathogenic germline mutations that can affect various organ systems. Radiologic screening and surveillance for solid tumors has emerged as a critical component of patient management in permitting early cancer detection. Although imaging surveillance may be tailored for organ-specific cancer risks, surveillance protocols frequently utilize whole-body MRI or PET/CT because of their ability to identify neoplasms in different anatomic regions in a single exam. In this review, we discuss the basic tenets of imaging screening and surveillance strategies in these syndromes, highlighting the more common neoplasms and their associated multimodality imaging findings. •Pathogenic germline mutations in hereditary cancers cause early-onset distinctive tumors in an organ-specific pattern.•Geneticist, oncologist, and radiologist coordination facilitates syndrome-appropriate screening and surveillance strategies.•WB-MRI is a promising comprehensive non-ionizing screening/surveillance modality but with sparse prospective survival data

Outcomes of metastatic synovial sarcoma with doxorubicin, pazopanib, and ifosfamide therapy

e23552 Background: Synovial sarcoma (SS) accounts for 5-10% of all soft tissue sarcoma. SS are aggressive tumors with a median 5-year survival of 60-70% when localized disease but also a propensity for metastatic spread with 40-45% of patients developing metastasis within 5 years. It is considered a chemotherapy-sensitive sarcoma and treatment options are increasing. Herein, we present the outcomes of SS patients by systemic regimen and multimodality approach. Methods: This is a single institution, retrospective cohort of 79 patients with histopathologically confirmed SS treated at from 2004 to 2019. Clinical characteristics, treatment, response and survival were analyzed. We estimated medians of progression-free survival (PFS) and overall survival (OS) using the method of Kaplan-Meier along with the Log-Rank test. All tests were two-sided and statistical significance was considered when p<0.05. Results: Median follow-up was 3.7 years (range 3.13 to 4.33), 59.5% were women and median age at diagnosis was 41 (range 5-77). At presentation, 60 patients (75.9%) had localized disease and 19 (24.1%) presented with metastatic disease. Among the entire cohort the three-year OS rate was 78.9% (95%CI = 66.3-87.3) and five-year OS rate 68.7% (95%CI = 53.5-79.9). OS between localized disease (N = 45) and metastatic (N = 12) was not statistically significant (log-rank p = 0.098). When comparing different regimens, doxorubicin-based regimens (DBR) showed longest median PFS of 10.1 months (95%CI = 3.97-21.16), while pazopanib had a median PFS of 7.45 (95%CI = 2.63-12.3), high dose ifosfamide (HDI) 6.4 months (95%CI = 2.79-15.5) and trabectedin 3.12 months (95%CI = 0.99-6.97). Conversely, patients with metastatic disease treated with pazopanib experienced a median PFS of 11.47 months (95%CI = 2.63-32.9) while those treated with a DBR 8.15 months (95%CI = 1.08-35.8). Conclusions: SS is highly aggressive and, in our cohort, patients with local presentation had non-significant difference in OS to the metastatic disease, this could be due to a small sample size or the high probability for relapse this tumor has. Chemotherapy with DBRs showed superiority to other regimens and pazopanib showed to be slightly superior when evaluating only metastatic disease. Addition of pazopanib maintenance therapy may improve PFS and OS. Continuous evaluation of these patients with further inclusion of SS on immunotherapy is warranted

Heterogenous Intertumoral KIT Mutations in Long-term Stage 4 Gastrointestinal Stromal Tumor Survivor

Abstract Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract, with a prevalence of 5% out of all sarcomas. We herein report the case of a 54-year-old man with metastatic GIST who initially presented to the emergency department with severe "anemia" CT examination revealed a 22 cm mass adherent to his small bowel and associated pelvic ascites and metastases. Surgical excision of the abdominal wall mass and partial omentectomy demonstrated extensive necrosis and a tumor mitotic rate of 17 per 5 mm2 . Molecular profiling of the primary mass showed a KIT exon 9 mutation. Despite eight years of sunitinib treatment, followup PET-CT evaluation showed three enlarging omental/peritoneal masses. Surgical excision and molecular profiling of each mass, opposed to the standard practice of profiling only one, demonstrated different KIT exon mutations between each mass, each with resistances to different tyrosine kinase inhibitor treatments. Article Highlights Metastatic gastrointestinal stromal tumor can attain novel mutations Performance of therapies may decline in the setting of novel KITmutations Molecular profiling of multiple metastatic nodules may aid in treating specific mutation