Ovarian Rhabdomyosarcoma

Primary ovarian rhabdomyosarcoma (RMS) is exceptionally rare. Histologies include embryonal, alveolar, spindle cell/sclerosing, and pleomorphic (adult). Care centers on surgical control when feasible and multi-agent sarcoma chemotherapy; radiotherapy is selectively used for local control. Due to rarity, treatment is individualized and often benefits from sarcoma/gynecologic oncology co-management and clinical trial evaluation.

• Desmin / myogenin / MyoD1 (positive) — myogenic differentiation
• PAX3–FOXO1 / PAX7–FOXO1 (occasional) — fusion oncoprotein
• DICER1 (occasional) — microRNA processing
• Ki-67 (common) — proliferation index
• MMR/MSI (rare) — DNA repair
• PD-L1 (variable) — immune checkpoint
• MYOD1 p.L122R (rare) — myogenic TF hotspot mutation (spindle/sclerosing RMS)
• TFCP2-related fusions (EWSR1::TFCP2 / FUS::TFCP2) (rare) — fusion-driven RMS subset with ALK upregulation
• FGFR4 (overexpression / activating mutations N535D/K, V550E/L) (occasional) — growth signaling receptor
• NTRK1/2/3 fusions (screen) (rare) — tumor-agnostic kinase fusion
• TMB (tumor mutational burden) (variable) — immunotherapy biomarker
• Cytokeratins (AE1/AE3), EMA, PAX8, WT1 (negative) — differential diagnosis (Müllerian carcinoma vs pure RMS); carcinosarcoma component ID
• SMARCB1/INI1 (positive) — SWI/SNF complex tumor suppressor
• PAX5 (pitfall) (rare) — B-cell TF; rare aberrant expression

• Myogenic transcriptional program — developmental
• PAX–FOXO1 fusion signaling (alveolar RMS) — invasion
• IGF–PI3K–AKT–mTOR axis — growth factor
• MAPK (RAS/RAF/MEK/ERK) — growth factor
• Hedgehog/GLI (subset) — growth factor
• Angiogenesis (VEGF) — angiogenesis

• Agents Database
• Protocols
• Alternative Therapies Guide
• Glossary
• Fasting / FMD
• Omega-3 (EPA/DHA)
• Melatonin
• G-CSF (filgrastim/pegfilgrastim)
• Dexrazoxane
• Mesna + aggressive hydration
• Photobiomodulation (low-level laser)
• Oral cryotherapy (ice chips)
• Duloxetine
• Acupuncture
• Exercise / Prehab program
• Vitamin D + calcium (bone health)
• Ginger (standardized extract)

• rarity: Ultra-rare; far <1% of primary ovarian malignancies
• medianAge: Bimodal: children/AYA (embryonal) and adults (pleomorphic/spindle); median highly variable
• annualIncidence: Not well established; limited to case reports and small series
• sex: Occurs only in women
• geographicVariation: Sporadic worldwide; registry underreporting likely
• riskFactors:
  • Possible association with DICER1 syndrome in pediatric gynecologic RMS contexts
  • Prior pelvic radiation (rare reports)
  • General sarcoma risk factors are nonspecific
  • Germline cancer-predisposition syndromes (consider TP53/Li-Fraumeni, DICER1) — screen history/pedigree; genetics referral when suspected
  • Prior therapeutic radiation or alkylating chemotherapy exposure — raises sarcoma risk; document timeline and fields
  • Long symptom-to-diagnosis interval — pelvic RMS presents nonspecifically; push for early imaging and tissue diagnosis when symptoms persist
  • Large initial tumor burden and nodal disease — prompt staging PET/CT or MRI pelvis/abdomen, and plan for combined-modality therapy
  • Incomplete prior resection (unplanned ‘whoops’ surgery) — re-staging and definitive oncologic resection planning at a sarcoma center
• prognosis: Prognosis is driven by stage at presentation, completeness of local control (R0 vs R1/R2), histology and fusion/mutation status, and early therapy response. Adverse biology includes PAX3–FOXO1–positive alveolar RMS, MYOD1 p.L122R spindle/sclerosing RMS, and TFCP2-fusion RMS. Tumor size (>5 cm), nodal disease, and metastasis at diagnosis worsen outcomes; adult RMS generally fares worse than pediatric/AYA. High-impact moves: (1) achieve complete resection when feasible with margin-appropriate radiation; (2) use risk-adapted systemic therapy with early response assessment (typically after 2–3 cycles) to change course if ineffective; (3) re-biopsy at progression to detect targetable switches; (4) discuss oligometastatic consolidations (SBRT, ablation, metastasectomy) case-by-case; and (5) refer early to a sarcoma center and prioritize clinical trials for fusion- or pathway-directed strategies.
• trends:
  • Delayed diagnosis is common due to nonspecific pelvic symptoms.
  • Management increasingly multidisciplinary (sarcoma + gynecologic oncology).
  • Earlier comprehensive profiling (RNA-seq fusion panel + DNA NGS) at diagnosis and first progression to guide trials and avoid dead-end therapy
  • Response-adapted care: objective reassessment after 2–3 cycles with protocolized switch when control is not achieved
  • Local control intensification: margin-informed radiation, SBRT for oligometastases (bone/spine), and selective ablation/embolization for liver lesions
  • Subset-directed trials: ALK-oriented strategies for TFCP2-fusion RMS; FGFR4-targeted approaches/biologics; BET/BRD4 or YAP/TEAD programs in fusion-driven RMS
  • Combination strategies to blunt resistance (e.g., dual PI3K/mTOR + MEK in RAS/AKT-active disease; anti-angiogenic add-ons in bulky, hypoxic tumors) in trial settings
  • MRD concepts entering sarcoma care: exploratory ctDNA/assays for trend-tracking alongside imaging (adjunctive, not decisive)
  • Supportive-care optimization as outcome lever: proactive neutropenia prevention, cardio-oncology for anthracyclines, early nutrition/rehab to keep dose intensity
  • Structured second-look and re-resection pathways when initial margins are positive or biology evolves
  • Earlier tumor board review for salvage plans, including metastasectomy candidacy and palliative-to-curative intent re-evaluation

• Malignant small round to spindle cells with rhabdomyoblastic differentiation; cross-striations occasionally visible.
• IHC: desmin+, myogenin+, MyoD1+; these are core diagnostic and essentially required to confirm RMS lineage.
• Variable cytokeratin and EMA staining—important in ovarian carcinosarcoma to distinguish the RMS vs carcinoma component; RMS usually negative.
• Subtypes: embryonal (including botryoid-like, often better prognosis), alveolar (usually PAX–FOXO1+, poor prognosis), spindle/sclerosing (MYOD1-mutant, poor prognosis, adult-leaning), pleomorphic (rare, adult, aggressive).
• PAX3–FOXO1 / PAX7–FOXO1 fusions: definitive for alveolar RMS; adverse prognosis, informs risk stratification, and required for some fusion-driven trial eligibility.
• MYOD1 p.L122R mutation: hallmark of spindle/sclerosing RMS; highly aggressive, therapy-resistant, often adult cases; prognostic red flag and an emerging trial keyword.
• TFCP2-related fusions (EWSR1::TFCP2 / FUS::TFCP2): aggressive variant with keratin/ALK expression; changes diagnosis, worsens prognosis, and may open eligibility for ALK-targeted or fusion-driven trials.
• FGFR4 hotspot mutations (N535/V550) or overexpression: frequent in RMS, especially alveolar; drive proliferation and metastasis. Currently trial targets (FGFR4 inhibitors, CAR-T).
• DICER1 alterations: rare but clinically relevant in pediatric/AYA RMS; if found, prompts germline testing and family counseling; may influence surveillance strategies.
• NTRK fusions (rare): qualify patients for tumor-agnostic TRK inhibitors (larotrectinib, entrectinib). High-impact if present.
• ALK protein overexpression (esp. TFCP2-fusion cases): potential therapeutic entry point; investigational ALK inhibitors being tested.
• SMARCB1/INI1 retention: distinguishes RMS from epithelioid sarcoma or malignant rhabdoid tumor; ensures accurate diagnosis.
• Ki-67 index: commonly >30–50%; not actionable, but confirms aggressive proliferation and supports intensity of systemic therapy.
• BET/BRD4 dependency in PAX–FOXO1+ RMS: epigenetic addiction; active area of BET inhibitor trials.
• YAP/TEAD activation (Hippo pathway dysregulation): contributes to invasion and resistance; early therapeutic exploration (TEAD inhibitors).
• p53–MDM2 axis: MDM2 overexpression can silence p53; MDM2 inhibitors under study, may re-sensitize tumors.
• Immune checkpoint markers: PD-L1 variable, TMB usually low, MSI rare; when positive, may qualify for checkpoint blockade, otherwise combination strategies are needed.
• Pathology markers should be used not only for diagnosis but also to triage into clinical trials (fusion-positive, ALK/FGFR4 targeted, NTRK tumor-agnostic, BET/epigenetic).
• Re-biopsy at progression is critical: RMS biology can evolve, and actionable targets (e.g., secondary ALK expression, novel fusions) may emerge.

• Pelvic/abdominal pain or pressure, increasing abdominal girth.
• Palpable adnexal mass on exam or imaging.
• Early satiety, constipation, urinary frequency from mass effect.
• Acute pain if torsion/rupture or hemorrhage occurs.
• Progressive unilateral pelvic or lower-back pain with sciatica-like radiation—nerve/foraminal encroachment in bulky disease.
• Ascites and abdominal distension out of proportion to appetite—consider capsular breach or peritoneal seeding.
• Flank pain or reduced urine output from ureteral compression/hydronephrosis; stent or nephrostomy may be required.
• Unilateral leg swelling or calf pain—possible DVT from pelvic mass effect or hypercoagulability.
• Bone pain (spine, pelvis, ribs) or inability to bear weight—suspect osseous metastasis or impending pathologic fracture.
• Cough, pleuritic chest pain, or exertional dyspnea—evaluate for pulmonary metastases or PE.
• Early satiety with unintentional weight loss, fatigue, or anemia of chronic disease—systemic burden.
• Irregular vaginal bleeding or discharge when adjacent Müllerian structures are secondarily involved.

• Hematogenous: lungs most common; bone and liver possible.
• Lymphatic: pelvic/para-aortic nodes can be involved (more so in alveolar RMS).
• Peritoneal: less dominant than epithelial OC but possible via capsular breach or tumor rupture.
• Local invasion into adjacent pelvic organs in bulky disease.
• Skeletal: axial skeleton (spine/pelvis) and ribs predominate; risk of cord compression in vertebral lesions.
• Pleural/pulmonary: parenchymal nodules ± pleural involvement; monitor for pneumothorax after lung procedures.
• Hepatobiliary: parenchymal metastases; rare biliary obstruction with capsular/porta involvement.
• Nodal patterns: alveolar biology increases nodal risk—evaluate pelvic/para-aortic basins; consider directed sampling of suspicious nodes.
• Iatrogenic seeding risk with capsule violation or unbagged extraction; rare port-site deposits after laparoscopy.

• No RMS-specific ovarian staging exists; many teams apply FIGO ovarian staging for anatomic extent.
• Risk-adapted therapy often follows rhabdomyosarcoma/soft-tissue sarcoma frameworks rather than epithelial OC algorithms.
• Comprehensive surgical staging principles from ovary (omentectomy, peritoneal evaluation) may be adapted case-by-case.
• Use sarcoma paradigms in parallel: document size (>5 cm), nodal status, and metastasis; margin status (R0/R1/R2) strongly influences local control strategy.
• Baseline staging set: MRI pelvis with contrast + CT chest (± abdomen/pelvis) or PET-CT; add bone imaging when pain or PET signal suggests osseous disease.
• Nodal assessment: lower threshold in alveolar or fusion-positive cases; sample suspicious pelvic/para-aortic nodes—sentinel mapping is not standard.
• Peritoneal management: avoid rupture/morcellation; use bagged extraction; consider peritoneal washings when capsule breach or ascites present.
• Operative planning: prioritize en-bloc R0 resection when feasible; place clips at close margins to guide adjuvant radiation fields.
• Pathology/molecular: request expedited IHC (desmin/myogenin/MyoD1) and send tissue for RNA fusion panel + DNA NGS at diagnosis; bank tissue for trials.
• Response-adapted staging: obtain early interval imaging (typically after 2–3 cycles); escalate/switch if inadequate response.
• Document ureteral involvement and stent timing relative to chemo/radiation; coordinate exchanges to minimize infectious complications.
• For recurrent/progressive disease: re-biopsy to confirm histology and capture evolved targets (e.g., new fusions/ALK expression) to unlock trials.

• MSI-H/dMMR (rare): may enable PD-1 blockade under tumor-agnostic approvals.
• IGF1R/PI3K/AKT/mTOR: pathway alterations support trial eligibility; single-agent activity historically limited.
• Hedgehog/GLI, MEK/ERK: investigational targets; consider baskets.
• Checkpoint inhibitors: modest activity overall; combinations under study.
• ctDNA/NGS can inform trial matching and detect resistance patterns.
• NTRK fusion (rare): TRK inhibitors (tumor-agnostic) can be high-yield when present.
• TFCP2-fusion subset: ALK overexpression—consider ALK-focused trials and keratin-positive RMS recognition.
• FGFR4 activation/overexpression: trial-focused FGFR4 inhibitors and emerging CAR-T approaches.
• PAX–FOXO1 epigenetic dependency: BET/BRD4 inhibition trials and transcriptional-complex disruption strategies.
• YAP/TEAD (Hippo dysregulation): early-phase TEAD inhibitor programs for resistance/stemness biology.
• p53–MDM2 axis: MDM2 antagonists in development—consider when TP53 wild-type and MDM2-high.
• DDR targeting (PARP/ATR) as radiosensitizers/combos in refractory disease—trial contexts only.
• Rational combos to blunt feedback (e.g., PI3K/mTOR + MEK) should be pursued in trials, not empirically off-label.

• Symptom-led: track pain, satiety, bowel/urinary changes, weight, and performance status.
• Imaging: CT chest/abdomen/pelvis every 8–12 weeks on active therapy; shorten to 6–8 weeks in aggressive courses.
• Tumor markers: CA-125/HE4 not reliable; consider LDH as nonspecific context only.
• Labs: CBC/CMP each cycle; watch for myelosuppression and hepatic/renal function shifts.
• Baseline and interval ECHO/MUGA with anthracyclines; consider troponin/BNP if symptoms or high cumulative dose.
• Ifosfamide monitoring: urinalysis (hematuria), creatinine/electrolytes (Fanconi), neuro checks for encephalopathy.
• Neuropathy tracking with vincristine/ifosfamide—dose-adjust to preserve function.
• VTE vigilance: new unilateral leg swelling or pleuritic chest pain warrants urgent evaluation.
• Post-therapy surveillance: tighter imaging in first 2 years (highest relapse risk), then spaced per sarcoma practice.
• Bone health: DEXA and vitamin D/calcium review when hypogonadism, steroids, or prolonged inactivity present.
• Port care and infection surveillance; prompt evaluation of fever ≥100.4°F (38.0°C).
• Use consistent imaging modalities/planes to improve response comparability; consider MRI pelvis for local assessment.

• Pain management with multimodal analgesia; early palliative care involvement improves QoL.
• Nutrition optimization to counter cachexia; involve oncology dietitian early.
• Management of bowel obstruction risk and postoperative adhesions.
• Psychosocial support and AYA-focused services when applicable.
• Growth-factor support per regimen risk and prior cycle neutropenia to preserve dose intensity.
• VTE prophylaxis/education individualized by surgery, immobilization, and TKI use; fast evaluation of leg swelling/SOB.
• Fertility preservation consults (oocyte/embryo banking) before gonadotoxic therapy when feasible; discuss ovarian suppression limitations.
• Cardio-oncology, nephrology, and pain/spine referrals early when organ-specific risks emerge.
• Neuropathy prevention/rehab: dose adjustments, PT/OT for balance and fine-motor function.
• Sleep, mood, and anxiety management—optimize antiemetics, pain plan, and behavioral supports to maintain resilience.
• Vaccination review (avoid live vaccines on active chemo); prompt antiviral/antibacterial prophylaxis per risk.
• Clear home plan for fever, dehydration, and port issues; provide direct lines and thresholds to avoid delays in care.

• Strong antioxidants on infusion days for ROS-dependent chemo may blunt efficacy.
• Anti-angiogenic drugs/supplements: avoid peri-operatively until wounds fully healed.
• CYP3A4/P-gp modulators can interact with anthracyclines/ifosfamide; review for interactions.
• Severe neutropenia/thrombocytopenia: avoid agents that worsen marrow suppression or bleeding risk.
• Grapefruit/Seville orange and St. John’s wort: avoid due to CYP3A4 effects on vincristine, TKIs, and other agents.
• Azole antifungals and macrolides (e.g., voriconazole, clarithromycin): strong CYP3A4 inhibitors—dose-adjust/avoid with vincristine and many TKIs.
• Rifampin and certain anticonvulsants (phenytoin, carbamazepine): strong enzyme inducers—can undermine chemo/TKIs.
• QT-prolonging combinations (many TKIs + antiemetics/antibiotics): check EKG and med list to avoid additive risk.
• Ifosfamide + nephrotoxins (NSAIDs, IV contrast close to dosing, aminoglycosides): heighten renal toxicity—coordinate timing and hydration.
• Planned surgery: hold VEGF-active TKIs/anti-angiogenic supplements well before and after to reduce bleeding and wound-healing complications.
• High-dose steroids can blunt checkpoint inhibitor efficacy; taper to physiologic doses when feasible before immunotherapy.
• Live vaccines contraindicated during active cytotoxic therapy; review vaccine plan for household contacts.
• Uncontrolled hypertension is a contraindication to starting/continuing VEGF TKIs—optimize BP first.
• Peripheral neuropathy: avoid or minimize agents/supplements that worsen neuropathy when on vincristine; escalate PT/OT early.
• Concurrent anticoagulation: coordinate with surgery/biopsy and anti-angiogenic agents to balance bleeding/clot risk.

• Fever ≥ 100.4°F (38.0°C) during chemo.
• Severe chest pain or sudden shortness of breath.
• Severe abdominal pain with peritoneal signs or obstipation.
• New focal neurologic deficit, seizure, or confusion.
• Heavy vaginal bleeding or hematemesis/melena.
• Oxygen saturation <92% at rest or rapidly worsening breathlessness.
• Back pain with leg weakness, numbness, saddle anesthesia, or loss of bladder/bowel control.
• No urine output (>8 hours) or severe flank pain with fever—concern for obstructive pyelonephritis.
• Continuous vomiting (>4 episodes in 6 hours) or inability to keep liquids down >12 hours.
• Syncope, severe dizziness, or signs of dehydration (very dry mouth, minimal urine, orthostasis).
• Severe allergic reaction to medication/infusion (wheezing, facial swelling, hives).
• Sudden severe headache with stiff neck or vision loss.
• Signs of sepsis: shaking chills/rigors, confusion, very low blood pressure, mottled skin.
• Sudden unilateral leg swelling/pain with warmth/redness (suspected DVT) or chest pain/SOB after leg symptoms (suspected PE).
• Uncontrolled pain not relieved by home medications.

• New/worsening pelvic or abdominal pain, bloating, or early satiety.
• Persistent diarrhea or mucositis not controlled with meds.
• Numbness/tingling/weakness suggesting neuropathy progression.
• Wound/port issues (erythema, drainage, fever).
• Medication/supplement changes or planned procedures.
• New or worsening back pain, gait changes, or leg weakness—even if mild or intermittent.
• Progressive leg swelling or new calf pain, especially after travel or reduced activity.
• Increasing abdominal girth/ascites or shortness of breath from abdominal pressure.
• Changes in urination: burning, urgency, flank pain, or notably decreased output.
• New jaundice, dark urine, pale stools, generalized itching, or RUQ discomfort.
• Low-grade fevers, chills, or night sweats lasting >48 hours.
• Poor oral intake, persistent nausea, or weight loss >5% over a month.
• Rash, mouth sores, or skin breakdown that interferes with eating or meds.
• Worsening neuropathy (dropping objects, balance issues) or new headaches.
• Planned dental work, surgery, or invasive procedures—confirm timing with chemo/anti-angiogenic agents.
• Difficult pain, anxiety, low mood, or insomnia affecting function—ask about adjustments or supports.
• Any new over-the-counter or herbal product—confirm interactions before starting.

• CT chest/abdomen/pelvis for baseline and follow-up.
• MRI pelvis for local anatomy and surgical planning.
• PET/CT in select cases with equivocal findings or to assess occult metastases.
• Low-dose dedicated chest CT at higher cadence during active therapy for early pulmonary detection.
• Whole-body MRI (where available) for marrow/bone mapping in AYA/pediatric-leaning disease.
• Targeted MRI liver with hepatobiliary contrast when CT/PET is equivocal.
• Spine MRI promptly for back pain/neurologic symptoms suggestive of cord compression.
• Use the same modality/planes across time points to improve response comparability.

• Stage and metastatic burden (lung, liver, bone).
• Histology: alveolar (PAX–FOXO1) generally worse than embryonal.
• Completeness of resection (R0/low residual).
• Age/performance status and treatment tolerance.
• MYOD1 p.L122R mutation (spindle/sclerosing) — adverse.
• TFCP2-fusion RMS — adverse; often ALK-high/keratin-positive.
• Tumor size >5 cm and nodal involvement (especially in alveolar biology).
• Early radiologic response after 2–3 cycles (CT/MRI ± PET) — guides escalation/switch.
• Number of metastatic sites and resectability of residual disease after response.
• Time to relapse (<12 months vs ≥12 months) and pattern (local vs distant).
• Feasibility of complete local control (surgery ± RT) at primary and oligomet sites.

• Curative-intent in localized disease with complete resection and systemic therapy.
• Disease-control for advanced/metastatic disease with systemic therapy ± RT.
• Symptom-led focus with palliative measures when appropriate.
• Curative-intent with neoadjuvant therapy to downstage to an R0 resection, then adjuvant therapy ± RT.
• Curative-path consolidation in oligometastatic disease: systemic response → SBRT/ablation/metastasectomy.
• Trial-first strategy when biology offers a strong match (e.g., NTRK, ALK, FGFR4, BET/TEAD, MDM2).
• Response-adapted plan with pre-agreed switch rules after 2–3 cycles to avoid ineffective therapy drift.
• Re-biopsy/re-profiling at progression to capture new targets that could open curative trial avenues.

• Analgesia optimization; consider palliative RT for painful lesions.
• Ascites/obstruction management if peritoneal involvement.
• Fatigue/anemia support, rehab, and psychosocial resources.
• Early palliative care co-management improves symptom control and treatment deliverability; escalate before crises.
• Bone/spine disease: SBRT for pain/local control; vertebroplasty/kyphoplasty when indicated; urgent pathway for cord compression signs.
• Liver-dominant symptoms: consider embolization/ablation consults for pain or cholestasis relief when systemic control is limited.
• Refractory ascites: serial paracentesis with albumin replacement or tunneled peritoneal catheter; diuretics help selected patients.
• Malignant bowel obstruction: NG decompression, octreotide, steroids, and selective stenting/surgery with goals-of-care alignment.
• Ureteral compromise: timely stent exchange or nephrostomy to preserve renal function and keep systemic therapy on track.
• Neuropathy and mucositis programs (PT/OT, oral care bundles, dose adjustments) to maintain dose intensity.
• VTE prevention/treatment education with clear ED triggers (leg swelling, pleuritic pain, hemoptysis).
• Sleep, mood, and appetite supports (CBT-I, dietitian, stimulant trials when appropriate) to sustain resilience.

• VAC (vincristine/actinomycin/cyclophosphamide) — pediatric/AYA (Foundation for pediatric RMS; adult tolerance varies. Use growth-factor prophylaxis; early response check at 2–3 cycles to decide on escalation or switch.)
• Doxorubicin/Ifosfamide variants — adult STS (Common adult sarcoma backbone; monitor cardiac/renal toxicity. Consider dexrazoxane for cardioprotection; strict mesna/hydration and CNS/renal monitoring for ifosfamide.)
• Gemcitabine/Docetaxel — recurrent/palliative (Soft-tissue sarcoma option; activity varies in RMS. Useful for symptom control and disease stabilization when curative options are limited.)
• VDC/IE (vincristine/doxorubicin/cyclophosphamide ↔ ifosfamide/etoposide) — high-risk/AYA-fit adult (Intensified alternating regimen; consider for bulky/biologically adverse disease to enable resection. Requires G-CSF, cardioprotection strategy, and tight toxicity monitoring.)
• IVA (ifosfamide/vincristine/actinomycin) — neoadjuvant/anthracycline-avoidant (Option when avoiding anthracyclines (cardiac risk) or as bridge to surgery; ensure mesna/hydration and neuro/renal surveillance.)
• VIT (vincristine/irinotecan/temozolomide) — relapsed/chemo-pretreated (Pediatric-relapse–derived; can debulk or stabilize to open local control windows. Watch GI toxicity and myelosuppression.)
• High-dose Ifosfamide — salvage (STS-standard salvage with occasional RMS responses; neuro/nephrotoxicity vigilance is essential. Consider when aiming to downstage for consolidative RT/surgery.)
• Doxorubicin/Dacarbazine (± Ifosfamide) — adult STS legacy (Historic backbone with modest RMS activity; consider case-by-case when other regimens contraindicated. Cardio and marrow safety planning required.)
• Oral maintenance (vinorelbine + low-dose cyclophosphamide) — post-response/investigational (Exploratory disease-control concept after good response; adult RMS data limited—prefer on protocol.)

• Fusion testing (PAX3/7–FOXO1) — Defines alveolar RMS biology; informs prognosis and opens fusion-driven trial options.
• NGS panel — Identifies pathway alterations (PI3K/AKT/mTOR, RAS/MAPK) and trial hooks; may detect DICER1.
• MMR/MSI — Rare biomarker enabling PD-1 blockade under tumor-agnostic approvals.
• Germline genetics (if indicated) — Evaluates DICER1 or other syndromic risks, especially in pediatric/AYA cases.
• MYOD1 hotspot (p.L122R) — Flags spindle/sclerosing biology with poor prognosis; prioritizes aggressive/neoadjuvant strategies and trial keywords.
• TFCP2 fusion panel (RNA-seq) — Identifies TFCP2-fusion RMS; often ALK-high/keratin-positive—supports ALK-focused trial eligibility.
• ALK IHC/NGS (expression/variants) — If high/altered, consider ALK inhibitor trials (esp. TFCP2-fusion subset).
• FGFR4 mutation/expression — Hotspots (N535/V550) or overexpression support FGFR4-targeted/CAR-T trial matching.
• pan-TRK IHC → confirmatory RNA fusion — NTRK fusion qualifies for tumor-agnostic TRK inhibitors; rare but high-yield.
• TMB (large-panel/whole-exome) — If unusually high, may support checkpoint inhibitor access or combination IO trials.
• MDM2 amplification (± p53 status) — MDM2 inhibitor trials in TP53–wild-type contexts.
• Baseline/serial ctDNA (exploratory) — Adjunct for trend-tracking and earlier switch decisions; can help capture resistance mechanisms for trial re-matching.

• ovarian rhabdomyosarcoma
• gynecologic rhabdomyosarcoma
• embryonal RMS ovary
• alveolar RMS PAX3-FOXO1
• soft tissue sarcoma ovary
• IGF1R PI3K mTOR trials
• MSI dMMR basket
• checkpoint inhibitor combinations
• AYA sarcoma trials
• TFCP2 fusion rhabdomyosarcoma
• ALK overexpression inhibitor trial
• FGFR4 inhibitor trial
• FGFR4 CAR-T solid tumor
• NTRK fusion TRK inhibitor
• BET inhibitor BRD4 fusion-positive sarcoma
• YAP TEAD inhibitor solid tumor
• MDM2 inhibitor p53 wild-type sarcoma
• MEK inhibitor RAS-mutant rhabdomyosarcoma
• dual PI3K/mTOR plus MEK combination trial
• MET HGF inhibitor sarcoma
• CXCR4 inhibitor solid tumor metastasis
• DDR PARP ATR inhibitor radiosensitization sarcoma
• anti-angiogenic VEGF TKI sarcoma combination
• SBRT oligometastatic sarcoma trial
• oligometastatic metastasectomy sarcoma
• tumor-infiltrating lymphocyte (TIL) therapy sarcoma
• oncolytic virus sarcoma
• dendritic cell vaccine sarcoma
• circulating tumor DNA sarcoma minimal residual disease
• adult rhabdomyosarcoma basket trial
• sarcoma basket fusion-positive
• NCI MATCH sarcoma
• ASCO TAPUR sarcoma
• EORTC sarcoma trial
• SARC consortium trial

• Fusion-positive (PAX–FOXO1) RMS basket trials.
• IGF1R/PI3K/AKT/mTOR targeted studies.
• MSI-H/dMMR immunotherapy baskets (rare).
• Combination IO + targeted/RT trials in sarcoma.
• AYA-focused sarcoma trials.
• TFCP2-fusion RMS with ALK-directed inhibitors (± combinations).
• FGFR4 inhibitor or FGFR4 CAR-T programs for RMS.
• NTRK fusion tumor-agnostic trials (TRK inhibitors).
• BET/BRD4 inhibitor trials in fusion-driven RMS.
• YAP/TEAD inhibitor trials for Hippo-dysregulated sarcoma.
• MDM2 inhibitor trials for TP53–wild-type, MDM2-high tumors.
• RAS/MAPK-directed (MEK inhibitor) trials for fusion-negative/RAS-mutant RMS.
• DDR strategies (PARP/ATR) ± RT/chemo in refractory sarcoma (protocol only).
• Anti-angiogenic VEGF TKI combination trials in sarcoma.
• Oligometastatic consolidation studies: SBRT/ablation/metastasectomy after systemic response.
• Cellular therapy explorations (TIL, dendritic vaccines, oncolytic viruses) in sarcoma baskets.

During active systemic therapy: imaging every 8–12 weeks (6–8 weeks if aggressive course or early relapse), with an early response check after 2–3 cycles to trigger escalation/switch if inadequate. Use CT chest at each interval (lungs = common hematogenous site) and MRI pelvis for local control planning; keep modality/planes consistent for RECIST comparability. If alveolar/fusion-positive or rapidly progressive disease, favor 6–8-week cadence and lower threshold for symptom-triggered scans. Cardiac monitoring on anthracyclines: baseline ECHO/MUGA, then ~every 3 months (or sooner if symptoms/cumulative dose rising); involve cardio-oncology early for borderline LVEF. Renal/neuro checks with ifosfamide each cycle (Fanconi labs, creatinine/electrolytes, mental status), and neuropathy checks with vincristine. In response/stable disease: extend to every 3–4 months with symptom-led adjustments; consider whole-body imaging if bone pain or TFCP2-fusion biology. Post-therapy surveillance: 3–6-month intervals for the first 2 years (highest relapse risk), then individualized (often every 6–12 months) with quicker reassessment for any new red flags. After metastasectomy/ablation/SBRT, obtain site-directed imaging at 6–8 weeks, then rejoin the standard cadence.

• Map neutropenia nadirs (often days 7–14) and schedule dental work/procedures outside nadir windows.
• G-CSF: start 24–72h after chemo when indicated; avoid same-day dosing with cytotoxics.
• With ifosfamide/cyclophosphamide, separate contrast CT by ≥48–72h when possible and ensure aggressive hydration to protect kidneys.
• Plan peri-operative holds for anti-angiogenic agents/supplements (≥4 weeks) and TKIs with VEGF activity; confirm BP control before restart.
• Time ureteral stent exchanges away from anticipated nadirs and coordinate antibiotic coverage.
• Coordinate infusion days with supportive meds (antiemetics, bowel regimen, neuropathy prophylaxis); avoid antioxidant-heavy days during ROS-dependent chemo.
• If experimenting with metabolic stressors (e.g., fasting-mimicking), schedule far from infusion days and under supervision to avoid dose-limiting weight loss.
• Sync cardiac imaging (ECHO/MUGA) with anthracycline cumulative dose milestones; prebook slots to prevent treatment delays.

• High-dose antioxidants ↔ infusion days for ROS-dependent regimens.
• Anti-angiogenic adjuncts ↔ peri-operative window.
• Strong CYP3A4/P-gp modulators ↔ anthracyclines/ifosfamide/vincristine without pharmacist review (e.g., azole antifungals, macrolides, rifampin, St. John’s wort).
• Grapefruit/Seville orange products ↔ vincristine/TKIs (CYP3A4 effects).
• Fish oil/high-dose curcumin/ginkgo ↔ anticoagulants or thrombocytopenia (bleeding risk).
• NSAIDs ↔ thrombocytopenia/ifosfamide renal stress without plan for renal and bleeding risk.
• Live vaccines ↔ active cytotoxic therapy; household vaccine plans should avoid exposing the patient to shed live virus.

• Track weight and lean mass; early dietitian referral with protein targets of ~1.2–1.5 g/kg/day if feasible.
• Use small, frequent, energy-dense meals for early satiety; consider oral nutrition supplements when intake falls.
• Address early satiety/constipation from mass effect with bowel regimen, hydration, and fiber titration (low-residue if obstruction risk).
• Hydration is therapy: prioritize fluid/salt strategies around ifosfamide/cyclophosphamide days to protect kidneys and bladder.
• Avoid restrictive diets in underweight/frail patients; any ketogenic/fasting approach should be supervised to preserve dose intensity.
• Neutropenia: food-safety counseling (avoid unpasteurized products/raw sprouts/undercooked meats); safe produce handling emphasized.
• Bone health: ensure vitamin D/calcium sufficiency and weight-bearing activity; consider DEXA when hypogonadism, steroids, or prolonged inactivity are present.

• Ports require infection vigilance; avoid local heat devices directly over port.
• Prior RT fields influence future planning; coordinate with radiation oncology.
• Port/central line: watch for erythema, tenderness, or arm swelling—evaluate for catheter-associated DVT; ultrasound if symptomatic.
• Ureteral stents/nephrostomy: schedule exchanges proactively; flank pain/fever or decreased output warrants urgent evaluation.
• Surgical clips/staples and mesh: provide operative notes to RT for artifact awareness and field design.
• Pacemaker/ICD or other implants: confirm MRI compatibility and respect RT dose constraints.
• Orthopedic hardware/spine instrumentation: anticipate imaging artifacts; collaborate on RT planning and positioning.
• Drains/ostomies: protect skin during RT; avoid beam hot spots and ensure device care during chemo hydration protocols.

• Cyclophosphamide-related cytopenias; monitor CBC closely.
• Ifosfamide nephrotoxicity/encephalopathy risk; watch creatinine and mental status.
• Anthracycline cardiotoxicity; follow LVEF and cumulative dose.
• Cyclophosphamide/Ifosfamide: hemorrhagic cystitis—urinalysis for hematuria; ensure mesna and aggressive hydration.
• Ifosfamide: Fanconi-like proximal tubulopathy—monitor bicarbonate, phosphate, potassium, glucose; watch for metabolic acidosis.
• Ifosfamide encephalopathy: new confusion/ataxia/hallucinations—stop drug; consider methylene blue per protocol.
• Vincristine: neuropathy, ileus, and SIADH—track neuropathic symptoms, bowel function, and sodium.
• Gemcitabine: myelosuppression/transaminitis; rare TMA—monitor platelets, creatinine, hemolysis labs if unexplained anemia.
• Docetaxel: febrile neutropenia/mucositis/edema—CBC and LFT surveillance; prophylaxis per risk.
• VEGF TKIs (if used): hypertension/proteinuria/hepatotoxicity—check BP, urine protein/creatinine ratio, and LFTs.
• Checkpoint inhibitors (if used): immune-related AEs—TSH, free T4, morning cortisol, LFTs; watch for colitis, pneumonitis, hepatitis, endocrinopathies.
• Cisplatin (if mixed histology): nephro- and ototoxicity—Mg/K and creatinine monitoring; baseline audiology when feasible.
• G-CSF: leukocytosis/bone pain—document timing 24–72h post-chemo and avoid same-day dosing.

• trial-eligibility
• trial-vs-standard
• toxicity-tolerance
• monitoring-plan
• goals-of-care
• adjunct-timing
• r0-priority
• neoadjuvant-candidate
• margin-status
• fusion-driven-strategy
• oligomet-consolidation
• dose-intensity
• cardio-oncology
• renal-protection
• neuropathy-prevention
• vte-prophylaxis
• gcsf-plan
• fertility-preservation
• stent-management
• re-biopsy-at-progression
• ctdna-trending
• pathway-combo-trials
• rt-fields
• imaging-cadence
• nutrition-plan
• tissue-banking
• care-at-sarcoma-center
• second-opinion
• expanded-access

• No randomized trials specific to primary ovarian RMS.
• Heterogeneous histology across small case series.
• Limited prospective data on adult RMS regimens in ovarian site.
• Unclear role of immunotherapy outside biomarker-selected trials.
• Comparative effectiveness of pediatric VAC-like vs adult STS backbones in adults with ovarian RMS.
• Optimal sequencing of surgery ↔ neoadjuvant/adjuvant therapy to maximize R0 rates.
• Defined indications/dosing for pelvic RT and nodal fields specific to ovarian RMS.
• Prospective value of ctDNA/MRD assays for response-adapted switches.
• Real-world outcomes of ALK/FGFR4/BET/TEAD/MDM2 targeted approaches in RMS subsets.
• Best criteria for oligometastatic consolidation (SBRT/ablation/metastasectomy) in potential cure pathways.
• Fertility-sparing oncologic safety data in very early unilateral disease.

• Which RMS subtype do I have (embryonal, alveolar, spindle/sclerosing, pleomorphic) and how does it change treatment?
• Is fertility-sparing surgery possible and safe in my case?
• Which chemo backbone is recommended for my age and subtype?
• Do I need radiation for margin-positive or nodal disease?
• Are there trials matched to my tumor’s drivers (e.g., PAX–FOXO1, PI3K/AKT/mTOR, MSI)?
• Can we send tissue for RNA fusion panel and DNA NGS now, and again at progression to capture targets (e.g., TFCP2, FGFR4, ALK)?
• Do we have enough banked tumor (FFPE + fresh-frozen) and a recent biopsy to qualify for molecular trials?
• What is the plan if there’s inadequate response after 2–3 cycles—what are our pre-agreed switch criteria?
• Am I a candidate for neoadjuvant therapy to improve the chance of an R0 resection?
• If disease is limited, could metastasectomy, ablation, or SBRT consolidate a systemic response?
• Would anthracycline cardioprotection (dexrazoxane) help preserve intensity without compromising efficacy?
• Should we involve a sarcoma specialty center or enroll via a national consortium (SARC, EORTC, NCI)?
• Are there basket trials for my biomarkers (FGFR4, ALK, NTRK, BET/BRD4, YAP/TEAD, MDM2)?
• Could we combine targeted agents with RT or chemo on a protocol to blunt resistance feedback (e.g., PI3K/mTOR + MEK)?
• What’s our VTE prevention plan and symptom-triggered pathway for urgent evaluation?
• How will we monitor for cardiac, renal, and neurotoxicity, and what dose-modification rules protect outcomes?
• Do I qualify for compassionate use / expanded access if a matched trial isn’t available?
• Is there a role for ctDNA as an adjunct to imaging for trend-tracking in my case?

• https://clinicaltrials.gov/search?term=rhabdomyosarcoma&cond=ovarian
• https://www.sarcomaalliance.org/clinical-trials/
• https://www.cancer.gov/about-cancer/treatment/clinical-trials/search?swKeyword=rhabdomyosarcoma

1. WHO Classification of Tumors: Soft Tissue and Bone (RMS chapters)

   WHO/IARC

   • Subtypes and diagnostic criteria
   • Pathology markers and fusions

2. PDQ® Childhood Rhabdomyosarcoma Treatment

   NCI

   • VAC-based regimens; RMS biology and staging concepts

3. ESMO–EURACAN–GENTURIS Clinical Practice Guidelines: Soft Tissue and Visceral Sarcomas

   ESMO

   • Adult STS backbones (doxorubicin/ifosfamide; gemcitabine/docetaxel)
   • Radiation/local control principles

4. Gynecologic tract rhabdomyosarcoma: clinicopathologic updates

   Peer-reviewed reviews/case series

   • Rarity and ovary-specific presentations
   • Patterns of spread and management nuances

5. Ovarian Rhabdomyosarcoma in Children - PMC

   PubMed Central / Authors: M.G. Pérez et al.

   • Subtypes (embryonal most common, alveolar, pleomorphic, spindle cell/sclerosing)
   • Biomarkers (desmin, MyoD1, myogenin positive; negative for pancytokeratin, etc.)
   • Pathology (rare, from stromal fibroblasts/endometriotic stroma)
   • Treatment (surgery, chemotherapy like VAC, selective radiotherapy)
   • Prognosis (aggressive, multimodal improves outcomes)
   • Overview and rarity

6. Molecular diagnostics in the management of rhabdomyosarcoma

   PubMed Central / Authors: M. Arnold et al.

   • Biomarkers (MYOD1 mutations, PAX3/7-FOXO1 fusions, RAS pathway mutations, NCOA2/VGLL2 fusions)
   • Subtypes and fusion-driven biology

7. Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathologic study

   ScienceDirect / Authors: J.A. Bennett et al.

   • Biomarkers (desmin positive, myogenin and MyoD1 often focal positive)

8. Myogenin is a Specific Marker for Rhabdomyosarcoma: An Immunohistochemical Study

   ResearchGate / Authors: G. Kumar et al.

   • Biomarkers (myogenin specific for RMS, desmin, MYOD1 define RMS)

9. Rhabdomyosarcoma - BINASSS

   BINASSS / Authors: Various (review)

   • Biomarkers (desmin, myogenin, MyoD1 positive; spindle cell RMS fusions)

10. Embryonal Rhabdomyosarcoma of the Ovary and Fallopian Tube: Rare Neoplasms Associated With Germline and Somatic DICER1 Mutations

    ResearchGate / Authors: W.G. McCluggage et al.

    • Biomarkers (DICER1 germline/somatic mutations in gynecologic RMS; some cases negative for desmin/myogenin/MyoD1 but atypical)

11. Biological Role and Clinical Implications of MYOD1 L122R Mutation in Rhabdomyosarcoma

    MDPI / Authors: I. Szymczak et al.

    • Biomarkers (MYOD1 p.L122R mutation in spindle/sclerosing RMS, aggressive subset)

12. Improving Individualized Rhabdomyosarcoma Prognosis Prediction: A Multimodal Machine Learning Approach

    medRxiv / Authors: L. Elouan et al.

    • Biomarkers (PAX3/PAX7-FOXO1 fusions as key prognostic markers)

13. The Emerging Role and Clinical Significance of PI3K-Akt-mTOR in Rhabdomyosarcoma

    PubMed Central / Authors: Various (2025 Review)

    • Pathways (PI3K-Akt-mTOR hyperactivation, proliferation, survival, resistance)
    • Resistance (therapy pressure and network redundancy)

14. Molecular Targets in Alveolar Rhabdomyosarcoma

    PubMed Central / Authors: Various

    • Pathways (PAX-FOXO1 transcriptional repression, interconnected mechanisms)

15. Molecular and Cellular Biology of Rhabdomyosarcoma

    Wiley Online Library / Authors: Various (2015, updated references)

    • Pathways (FGF signaling, IGF1-R-PI3K-mTOR, ERK/MAPK)
    • Resistance (apoptosis prevention, cross-activation)

16. Signaling Pathways that Overactivate Metabolism in Cancer

    JRPMS / Authors: Various

    • Pathways (PI3K/AKT/mTOR reprogramming glucose metabolism, tumor progression)

17. Signaling Pathways in Rhabdomyosarcoma Invasion and Metastasis

    ResearchGate / Authors: Various

    • Pathways (PAX-FOXO1, IGF/RAS/MEK/ERK, PI3K/AKT/mTOR, cMET, FGFR4)
    • Resistance (parallel activation, RTK upregulation)

18. Targeting the Hedgehog Pathway in Rhabdomyosarcoma

    MDPI / Authors: Various

    • Pathways (Hedgehog/GLI oncogenic role, stemness, proliferation)
    • Resistance (pathway bypass, limited monotherapy)

19. Redox Biology in Rhabdomyosarcoma

    ScienceOpen / Authors: Various (2019)

    • Pathways (IGF1R, FGFR, EGFR leading to mTOR via PI3K/AKT)
    • Angiogenesis (VEGF involvement)

20. Targeting Hedgehog and PI3K/AKT/mTOR in RMS

    Semantic Scholar / Authors: Geyer et al. (2018)

    • Pathways (PI3K/AKT/mTOR importance, regulation of HH signaling)
    • Resistance (feedback loops)

21. PI3K/AKT/mTOR Pathway in Angiogenesis

    Frontiers / Authors: Various

    • Pathways (PI3K role in angiogenesis, normal/cancer tissues)

22. Molecular Drivers of PAX3/7-FOXO1 Tumorigenesis

    BioMed Central / Authors: Various (2012)

    • Pathways (PAX-FOXO1 cooperating genes, target genes for tumorigenesis)

23. Current Evidence and Directions for Intermittent Fasting During Chemotherapy

    PubMed Central / Authors: Various

    • Adjuncts (Fasting/FMD as adjunct to chemotherapy, safety, effects on nutritional status)

24. Review of Under-Recognized Adjunctive Therapies for Cancer

    PubMed Central / Authors: Various

    • Adjuncts (Melatonin for circadian reset, sleep improvement in cancer)

25. Review of Fasting-Mimicking Diets in Cancer Treatment

    News-Medical / Authors: Various (2024)

    • Adjuncts (Cyclic fasting/FMD role in cancer therapy, enhancing efficacy)

26. Short-Term Fasting Synergizes with Solid Cancer Therapy

    MDPI / Authors: Various (2022)

    • Adjuncts (Fasting diets boosting antitumor immunity, synergizing with therapy)

27. Fasting-Mimicking Diet in Patients Undergoing Active Cancer Treatment

    ClinicalTrials.gov / Authors: Various

    • Adjuncts (Pilot trial on 5-day FMD feasibility/safety during cancer treatment)

28. Fasting Mimicking Diet May Be Safe, Effective as Adjunct to Chemo

    Cancer Network / Authors: Various (2020)

    • Adjuncts (FMD safe/effective adjunct to chemo, general oncology)

29. Fasting and Fasting Mimicking Diets in Cancer Prevention and Therapy

    ScienceDirect / Authors: Various

    • Adjuncts (Fasting/FMD enhancing chemo, hormone therapy, immunotherapy)

30. Fasting as Cancer Treatment: Myth or Breakthrough in Oncology

    Cureus / Authors: Various (2025)

    • Adjuncts (Fasting reducing tumor growth, enhancing chemo sensitivity)

31. Immunomodulation after a Fasting Mimicking Diet Analyzed

    ASCO / Authors: Various

    • Adjuncts (FMD promoting CD8+ T-cell infiltration, decreasing Tregs)

32. Therapeutic Fasting in Reducing Chemotherapy Side Effects

    MDPI / Authors: Various (2023)

    • Adjuncts (Fasting as adjunct to chemo, effects on side effects)

33. Emergency Care for Ovarian Cancer: When to Call Your Doctor

    Not These Ovaries / Authors: Various (2025)

    • Red flags/Emergencies (Sudden chest pain, shortness of breath, fever during chemo, abdominal pain)
    • When to call (Persistent symptoms, dehydration)

34. Ovarian Cancer Red Flags: Help Prevent Delayed Diagnosis

    PubMed / Authors: Various (2024)

    • Red flags (Unexplained abdominal lump, bloating, sterile urine samples)
    • When to call (Recurrent urinary symptoms, new IBS in >50s)

35. Mode of Referral of Ovarian Cancer Patients

    PubMed Central / Authors: Various

    • Red flags (GPs/ED identifying symptoms for referral)

36. Ovarian Cancer Red Flags: What to Know

    MDedge / Authors: Various (2024)

    • Red flags (Recurrent urinary symptoms, sterile urine)

37. Rhabdomyosarcoma Stages and Risk Groups

    American Cancer Society / Authors: Various (2025)

    • Red flags (Metastasis assessment, bone marrow involvement)

38. Referral to a Specialist for Symptoms of Ovarian Cancer

    Cancer Research UK / Authors: Various (2025)

    • Red flags (Unexplained abdominal lump, urgent referral)

39. Ovarian Cancer Red Flags: Help Prevent Delayed Diagnosis

    ResearchGate / Authors: Various (2024)

    • Red flags (Symptoms warranting investigations, peritoneal signs)

40. Ovarian Cancer Red Flags

    Target Ovarian Cancer / Authors: Various

    • Red flags (Sterile urine, new IBS >50s, abdominal girth increase)

41. NCCN Guidelines for Patients: Ovarian Cancer

    NCCN / Authors: Various

    • Red flags/Emergencies (Abnormal blood counts, health issues signaling problems)

42. Ovarian Cancer Staging

    OCRA / Authors: Various

    • Red flags (High-grade atypical cells, metastasis likelihood)

43. Rhabdomyosarcoma: Current Therapy, Challenges, and Future Directions

    PubMed Central / Authors: Various

    • Complications (Surgical side effects, orbital RMS blindness)
    • Pathways/Adjuncts (General multimodal therapy)

44. Molecular Review of Ovarian Rhabdomyosarcoma in Children

    PubMed / Authors: M.G. Pérez et al. (2025)

    • Overview (Rare, presents in young children, favorable site)

45. Current and Future Treatment Strategies for Rhabdomyosarcoma

    Frontiers / Authors: Various

    • Adjuncts (Targeted therapies, multi-modality frontline)

46. The Emerging Role of PI3K-Akt-mTOR in Rhabdomyosarcoma

    MDPI / Authors: Various

    • Pathways (PI3K-Akt-mTOR role, targeted therapies)

47. Molecular Review of Rhabdomyosarcoma

    MalaCards / Authors: Various

    • Pathways (Molecular drivers in RMS)

48. Case Report: Uterine Embryonal Rhabdomyosarcoma

    Frontiers / Authors: Various (2025)

    • Symptoms/Complications (Prolonged diagnostic process in gynecologic RMS)

49. Signs and Symptoms of Rhabdomyosarcoma

    American Cancer Society / Authors: Various (2025)

    • Red flags (Lump/swelling, abdominal pain, dyspnea)

50. Diagnosis and Treatment of Rhabdomyosarcomas

    Via Medica / Authors: Łomiak et al. (2023)

    • Symptoms (Head/neck, urogenital, abdominal presentations)

51. Rhabdomyosarcoma: Symptoms, Prognosis & Treatment

    Cleveland Clinic / Authors: Various

    • Red flags (Nosebleeds, vomiting, lumps, similar to less serious conditions)

52. Molecular Diagnostics in the Management of Rhabdomyosarcoma

    PubMed Central / Authors: M. Arnold et al.

    • Pathways (PAX3/7-FOXO1 fusions, FGFR4, MET, Hippo)
    • Resistance (Not explicitly, but network implications)

53. Biological Role and Clinical Implications of MYOD1 L122R Mutation in Rhabdomyosarcoma

    MDPI / Authors: I. Szymczak et al.

    • Pathways (Myogenic transcriptional program, MYOD1 role in differentiation block, MYC-like activity)

54. Childhood Rhabdomyosarcoma Treatment (PDQ®)

    National Cancer Institute / Authors: Various

    • Adjuncts (Chemotherapy regimens like VAC, radiation techniques, surgery)
    • Red flags/Emergencies (Metastatic complications, recurrence management)
    • Ovarian applicability (Genitourinary sites, conservative surgery)

55. Evolving Classification of Rhabdomyosarcoma - PMC

    PubMed Central / Authors: Various (2023)

    • Subtypes (embryonal, alveolar, spindle/sclerosing, pleomorphic)
    • IHC (desmin+, MyoD1+, myogenin+)
    • Molecular (PAX3/7-FOXO1 fusions, MYOD1 mutations, TFCP2 fusions)

56. Embryonal rhabdomyosarcoma - Pathology Outlines

    Pathology Outlines / Authors: Various (2025)

    • Histology (small round/spindle cells, rhabdomyoblastic differentiation)
    • IHC (desmin+, myogenin+, MyoD1+; negative cytokeratin/EMA)
    • Molecular (no FOXO1 fusion in embryonal; high Ki-67)

57. Fusion-driven Spindle Cell Rhabdomyosarcomas of Bone and Soft Tissue

    Modern Pathology / Authors: Various (2023)

    • Molecular (TFCP2 fusions with ALK expression, desmin/MyoD1+)
    • Subtypes (spindle cell RMS)
    • IHC (ALK+, keratin+ in TFCP2 cases)

58. Identification of FGFR4-activating Mutations in Human Rhabdomyosarcomas

    PubMed / Authors: Various (2009)

    • Molecular (FGFR4 mutations N535/V550 activating, frequent in alveolar RMS)
    • Translational (oncogene function, trial targets)

59. Embryonal Rhabdomyosarcoma of the Uterine Corpus: Molecular Analysis Highlighting DICER1 Association

    ScienceDirect / Authors: J.A. Bennett et al. (2023)

    • Molecular (DICER1 alterations in gynecologic RMS)
    • IHC (variable myogenin/MyoD1)
    • Clinical (re-biopsy, trial triage)

• Alternative Therapies Guide
• Agents Database
• Protocols

• Educational resource; not medical advice. Coordinate decisions with sarcoma and gynecologic oncology.
• Highlight clinical trial opportunities whenever feasible due to rarity.