Pain Management of Spinal Metastatic Lesions from Ovarian Clear Cell Carcinoma

1. Pharmacological Management (WHO Analgesic Ladder)

Step 1 — Mild Pain

• Paracetamol (acetaminophen) 500–1000 mg q6h (max 4 g/day)
• NSAIDs (e.g., ibuprofen, naproxen, ketorolac) — particularly useful for bone pain due to their anti-prostaglandin activity
  • Use with a PPI for GI protection; monitor renal function
  • NSAIDs may have additive benefit with opioids for osteolytic metastatic pain

Step 2 — Moderate Pain

• Weak opioids: codeine, tramadol, low-dose oxycodone
• ESMO alternative: Low-dose strong opioids (e.g., morphine 5–10 mg orally q4h) can be used instead of weak opioids to avoid the "ceiling effect"

Step 3 — Severe Pain

• Prescribe a regular (around-the-clock) dose plus breakthrough doses (10–15% of total daily opioid dose, available q1–2h PRN)
• Titrate every 24–48 hours as needed
• Always co-prescribe a bowel regimen (e.g., senna + macrogol); antiemetics PRN

Adjuvant Analgesics (Co-analgesics)

2. Radiation Therapy (RT)

Fractionation Schedules

Special consideration for OCCC: Clear cell carcinoma is considered relatively radioresistant compared to high-grade serous carcinoma. Stereotactic radiosurgery (SRS/SBRT) delivers ablative doses with high precision and is preferred when technically feasible, particularly for intact vertebral body lesions without significant epidural disease.

3. Interventional & Surgical Approaches

Minimally Invasive Procedures

Surgical Intervention

• Spinal cord compression or instability (Spinal Instability Neoplastic Score [SINS] ≥ 13)
• Neurological deterioration
• Failure of radiotherapy
• Need for tissue diagnosis

Epidural/Intrathecal Analgesia

• Epidural steroid injections for localized radicular pain
• Intrathecal drug delivery systems (IDDS): morphine ± ziconotide via implanted pump — highly effective for refractory cancer pain, reduces systemic opioid burden and side effects

4. Systemic Oncological Therapy

Chemotherapy

• First-line: Carboplatin + paclitaxel (standard; limited efficacy for clear cell)
• Second-line/recurrent: Gemcitabine, irinotecan, oxaliplatin, or clinical trials

Targeted/Immunotherapy

• mTOR inhibitors (everolimus, temsirolimus) — have activity in PIK3CA-mutated OCCC
• Immune checkpoint inhibitors (pembrolizumab, nivolumab) — OCCC has higher mutational burden than serous subtype; responses reported, especially in MSI-H tumors
• HER2-targeted therapy — small subset of OCCC overexpresses HER2
• PARP inhibitors — limited role unless BRCA-mutated
• Molecular tumor board referral is strongly encouraged

5. Non-Pharmacological & Supportive Measures

• Spinal orthosis/bracing: Cervicothoracic or thoracolumbar orthoses to reduce mechanical pain during mobilization
• Physiotherapy: Careful weight-bearing advice, gait aids, fall prevention
• Transcutaneous Electrical Nerve Stimulation (TENS): Adjunct for localized pain
• Psychological support: CBT, mindfulness for chronic cancer pain; address pain catastrophizing
• Palliative care integration: Early palliative care referral improves pain control, QoL, and potentially survival

6. Emergency: Metastatic Spinal Cord Compression (MSCC)

1. Dexamethasone 16 mg IV/PO STAT, then 4 mg q6h
2. Urgent MRI whole spine (within 24 hours, or immediately if neurological signs)
3. Neurosurgical/radiation oncology referral within 24 hours
4. DVT prophylaxis if immobile

Summary Algorithm

Spinal Metastatic Pain (OCCC)
         │
         ├─ Mild → Paracetamol ± NSAID + adjuvants
         ├─ Moderate → Weak opioid or low-dose strong opioid + adjuvants
         └─ Severe → Strong opioid (titrate) + dexamethasone + adjuvants
                          │
                          ├─ Radiation: EBRT or SBRT (preferred for OCCC)
                          ├─ Interventional: vertebroplasty/kyphoplasty/RFA
                          ├─ Surgical: if MSCC, instability, or cord compression
                          ├─ Intrathecal pump: if refractory systemic opioids
                          └─ Systemic therapy: PIK3CA-mTOR, ICI, clinical trial

• Cancer Pain Management in Adults — ESMO/WHO Guidelines, p. 13
• External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases — Clinical Practice Guideline, p. 9
• ESMO Clinical Practice Guidelines: Metastatic Bone Disease
• NCCN Guidelines: Adult Cancer Pain, Ovarian Cancer (Clear Cell Histology)

Hoarseness of Voice in Metastatic Ovarian Clear Cell Carcinoma

Primary Mechanism: Recurrent Laryngeal Nerve Palsy

Anatomy — Why the RLN is Vulnerable

• Arises from the left vagus nerve (CN X) at the level of the aortic arch
• Loops under the arch of the aorta (around the ligamentum arteriosum)
• Ascends in the tracheo-oesophageal groove to reach the larynx and supply all intrinsic laryngeal muscles except the cricothyroid
• Any mass in the left mediastinum, aortopulmonary window, or left paratracheal region can compress or invade it

Clinical Features of RLN Palsy

Compensation: Symptoms may partially resolve within weeks as the contralateral vocal fold adducts across the midline to meet the paralysed cord.

How Metastatic OCCC Causes RLN Palsy

1. Mediastinal Lymph Node Metastases

• OCCC can spread via lymphatics to para-aortic → retrocural → posterior mediastinal → paratracheal lymph nodes
• Enlarged nodes in the aortopulmonary window or left paratracheal chain compress the left RLN
• This is the most common mechanism in gynaecological cancers causing hoarseness

2. Pulmonary / Pleural Metastases

• OCCC metastasises to the lungs; hilar or mediastinal involvement from pulmonary metastases can entrap the RLN
• Malignant pleural effusion with mediastinal shift can stretch the nerve

3. Direct Mediastinal Invasion

• Advanced or recurrent OCCC with direct transdiaphragmatic extension into the posterior mediastinum
• Rare but described in peritoneal carcinomatosis with cephalad spread

4. Spinal Metastases (Relevant to This Case)

• Cervicothoracic vertebral metastases (C5–T4 level) with epidural or paravertebral mass extension can compress the vagus nerve trunk or the RLN at its origin
• Given the prior context of spinal metastases in this patient, paravertebral soft-tissue extension at a cervicothoracic level compressing the vagus/RLN is a direct consideration

Other Causes of Hoarseness to Consider

Diagnostic Approach

1. Laryngoscopy (flexible nasopharyngoscopy): Confirms vocal cord mobility — unilateral cord paralysis in paramedian position is diagnostic of RLN palsy
2. CT chest + neck with contrast: Identifies mediastinal lymphadenopathy, paravertebral masses, pulmonary metastases, or direct nerve compression
3. MRI cervicothoracic spine: If spinal metastases are present, assess for paravertebral soft-tissue component at C5–T4 levels
4. PET-CT: Maps full extent of metastatic disease including mediastinal nodes

Summary