Eribulin and Radiation Therapy in Treating Patients With Retroperitoneal Liposarcoma That Can Be Removed by Surgery

Prior treatment

• Presence of distant metastases; intra-abdominal (regional) spread is allowable if meets inclusion criterial indeterminate or small volume pulmonary nodules may be eligible, if the treating physicians recommend curative-intent resection of the primary tumor despite the presence of possible lung metastases
• Prior radiation or systemic therapy for the diagnosis of liposarcoma
• Prior eribulin
• Concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of malignancies that have completed therapy and are considered by their physician to be at less than 30% risk of relapse; prior systemic therapy is allowed with the exception of prior eribulin; prior radiation therapy is allowed with the exception of any abdominal, pelvic or retroperitoneal radiation \> 10 Gy
• Use of more than one medication with a known risk of TdP
• Major operation within 14 days prior to starting study drug or not recovered from surgical complications; neither tumor biopsy nor central line insertion are considered a major operation
• Active infection; any systemic antimicrobial therapy must be completed \>= 5 days prior to initiation of protocol therapy
• Pregnant or nursing (lactating) individuals; NOTE: Pregnant individuals are excluded from this study because eribulin is an investigational agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the individual with eribulin breastfeeding should be discontinued; these potential risks may also apply to doxorubicin
• Unable or unwilling to stop the use of herbal supplements; the use of marijuana or its derivatives is allowed; the use of supplements may be allowed after review by a study pharmacist to confirm no significant risk of interaction with eribulin or radiation

Lab values

• History of uncontrolled arrhythmia, congenital long QT syndrome or torsades de pointes (TdP)

Other

• Grade \>= 2 peripheral neuropathy
• Contraindication to magnetic resonance imaging (MRI), including presence of a pacemaker or aneurysm clip, severe claustrophobia, a known reaction to gadolinium contrast, or body weight exceeding 300 pounds (lbs)

• Pathologically confirmed diagnosis of liposarcoma; all subtypes are eligible
• Sufficient archival tissue available for correlative studies; submission of formalin-fixed paraffin-embedded (FFPE) tumor tissue from a previous biopsy or resection is required, and the most recent specimen is preferred; if a FFPE block cannot be provided, then 10 unstained, positively-charged slides of 4-5 um thickness must be submitted; if insufficient archival tissue is available, a repeat biopsy will be necessary
• Primary or recurrent retroperitoneal, scrotal/spermatic cord or abdominal tumor
• For subjects between the ages of 12-18 years only, body surface area (BSA) must be \>= 1.5 m\^2
• All sites of disease must be resectable or borderline resectable as assessed by a surgical oncologist with experience in retroperitoneal sarcoma resection after discussion in our institutional multidisciplinary sarcoma tumor board conference
• All sites of disease must be targetable with intensity-modulated radiation therapy (IMRT) with acceptable morbidity and without exceeding normal tissue dose constraints as assessed by a radiation oncologist
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at time of screening
• Fridericia's correction formula (QTcF) interval on standard 12-lead electrocardiography (ECG) parameters at screening (defined as the mean of the triplicate ECGs) of \< 450 msec for males and \< 470 msec for females
• Ejection fraction of \>= 50%
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Individuals of childbearing potential must be willing to use adequate contraception throughout the study and for 3 weeks after study drug discontinuation
• Absolute neutrophil count (ANC) \>= 1 K/cu mm
• Platelets (no transfusion within prior 7 days) \>= 100 K/cu mm
• Hemoglobin (no transfusion within prior 7 days) \>= 9.0 g/dL
• Total bilirubin \< institutional upper limit of normal (ULN), except for subjects with documented Gilbert's syndrome, for which =\< 3.0 x ULN or direct bilirubin =\< 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN
• Estimated creatinine clearance \> 50 mL/min by Cockcroft-Gault equation
• Ability to understand and the willingness to sign a written informed consent document; subject has signed the informed consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements