What is the recommended adjuvant therapy for leiomyosarcoma of the stomach?

Adjuvant Therapy for Gastric Leiomyosarcoma

For gastric leiomyosarcoma, the recommended adjuvant therapy is doxorubicin-based chemotherapy, which may be considered for high-risk patients (high-grade, deep, >5 cm tumors) following complete surgical resection. 1

Surgical Management as Primary Treatment

• Complete surgical resection with negative margins remains the cornerstone of treatment for gastric leiomyosarcoma 2
• Wedge resection or partial gastric resection is acceptable as long as negative margins can be achieved 2

Adjuvant Chemotherapy Options

First-line Options:

• Doxorubicin-based regimens:
  • Single-agent doxorubicin is considered standard first-line treatment for high-risk patients 1
  • Doxorubicin plus ifosfamide may be considered when a higher response rate is desired in patients with good performance status 1
  • For leiomyosarcoma specifically, doxorubicin plus dacarbazine is preferred over regimens containing ifosfamide, as ifosfamide has shown less convincing activity in leiomyosarcoma 1
  • The most recent evidence shows doxorubicin plus trabectedin followed by trabectedin maintenance significantly improves progression-free and overall survival compared to doxorubicin alone in advanced leiomyosarcoma 3

Decision-Making for Adjuvant Therapy:

• Adjuvant chemotherapy is not standard treatment for all soft tissue sarcomas but can be proposed for high-risk patients (high-grade, deep, >5 cm tumors) 1
• The decision should be made after multidisciplinary evaluation, considering:
  • Tumor grade (high-grade tumors benefit most) 1
  • Tumor size (>5 cm increases risk) 1
  • Depth of invasion 1
  • Margin status after resection 2

Second-line and Subsequent Treatment Options

• Trabectedin has proven effective in leiomyosarcoma after failure of anthracycline-based therapy 1
• Gemcitabine with or without docetaxel has shown activity in leiomyosarcoma 1
• Dacarbazine has demonstrated activity as second-line therapy in leiomyosarcoma 1
• Gemcitabine plus dacarbazine has shown improved overall survival and progression-free survival over dacarbazine alone in a randomized trial 1
• Pazopanib is an option in non-adipogenic soft tissue sarcomas after progression on standard chemotherapy 1

Special Considerations

• Hormonal factors: Approximately 50% of uterine leiomyosarcomas express estrogen and/or progesterone receptors, suggesting potential hormone sensitivity that may extend to gastric leiomyosarcomas 4
• Hormone replacement therapy containing estrogens should be avoided in patients with leiomyosarcoma due to potential growth-promoting effects 4
• For patients requiring management of menopausal symptoms, non-hormonal approaches should be considered first-line 4

Treatment Algorithm

1. Complete surgical resection with negative margins
2. Risk assessment based on:
   • Tumor grade (high vs. low)
   • Size (>5 cm vs. <5 cm)
   • Depth (deep vs. superficial)
   • Margin status
3. For high-risk patients (high-grade, deep, >5 cm):
   • Consider doxorubicin-based adjuvant chemotherapy 1
   • Preferred regimen for leiomyosarcoma: doxorubicin + dacarbazine 1
   • Alternative: doxorubicin + trabectedin based on recent evidence 3
4. For low-risk patients:
   • Observation with regular follow-up 1

Follow-up Recommendations

• High-grade patients should be followed every 3-4 months in the first 2-3 years, then twice a year up to the fifth year, and once a year thereafter 1
• Follow-up should include appropriate imaging to detect recurrence 1

Pitfalls and Caveats

• Misdiagnosis is common - before KIT immunohistochemistry, gastrointestinal stromal tumors (GISTs) were often misdiagnosed as leiomyosarcomas 5
• Ensure proper pathological diagnosis with appropriate immunohistochemistry to differentiate from GIST 5
• The value of adjuvant chemotherapy remains controversial with conflicting study results, though meta-analyses suggest benefit in high-risk patients 1
• Treatment decisions should be made in centers with expertise in sarcoma management 1