Uncommon/Rare Cancers

For SCE Medical Oncology exam: sarcomas, GISTs

Insulinoma

·        Hypoglycaemia and associated symptoms: light headedness, irritable, sweats, palpitations

·        Usually involves the tail of the pancreas

·        Treatment: usually surgical resection preferable

o   If not fit for surgery – diazoxide reduces insulin secretion

o   50% can benefit from ocreotide

·        Malignant → doxorubicin and streptozocin

Glucagonoma

Can cause hyperglycaemia and diarrhoea

VIPoma

Causes excess vasoactive intestinal peptide

·       Usually cause flushing, watery diarrhoea and abdominal pain, hypoK, low stomach acid

·       Somatostatin analogue = ocreotide

·       2^nd line

o   Ki-67 low = everolimus or sunitinib

o   Ki-67 high = chemotherapy

GIST

Positive for c-kit/CD117 & DOG1 (95%)

~60-65y/o, stomach (~60%), small bowel (~30%)

Rarely spread to lymph nodes - thus, no nodal clearance needed at resection

Genetics: NF1, kit, PDGFRA, SDHC, BRAFmut

Early GIST treatment

Small gastric GISTs (<2 cm, asymptomatic, low mitotic index) may be observed with surveillance. Surgery for resectable disease. Imatinib 400 mg daily for high-risk GIST (adjuvant, 3 years).

·       KIT exon 11 = responds well to imatinib.

• KIT exon 9 = resistance, may need 800mg imatinib.

• PDGFRA D842V = resistant to imatinib.

Common tox imatinib: anaemia, periorbital oedema, rash, GI tox, muscle cramps

Metastatic GIST treatment

1L: First-line imatinib 400 mg - if KIT exon 9, consider increased dose

2L: sunitinib; 50mg 4 weeks on, 2 weeks off

3L: regorafenib

4L: Ripretinib.

Ewing Sarcoma

t(11;22)(q24;q12), EWSR1::FLI1 gene fusion

“small round blue cell tumour”

Poor prognosis: male, >14y/o, poor histological response to chemo (<95% necrosis), mets, bulky disease

Localised Mx: 14x cycles alternate chemo. VDC/IE 9 cycles induction → surgery → 5 cycles VC/IE

Metastatic Mx: same chemo, consider RT/resection to primary or lung

Osteosarcoma

~20-24y/o, no specific translocation

Rb1, TP53 associated

Less radiosensitive than Ewing.

Localised Mx: 2x neoadj MAP → surgery → 2x MAP & 2x MTX + Doxorubicin. Also: mifermertide.

^ size cut-off: <8cm

Metastatic Mx: same chemo, consider surgery to primary + mets.

Synovial sarcoma

SS18;SSX translocation

Can consider neo-adjuvant chemo if on extremity/trunk/chest wall

Liposarcoma

MDMZ presence

1L: Doxorubicin ± ifosfamide

2L: Eribulin

Leiomyosarcoma

Metastatic tx: Doxorubicin/dacarbazine

2L: trabectedin

Angiosarcoma

CD31, CD34, ERG, Factor VIII-related antigen

Common in breast patients due to adjuvant RT (years later) and chronic lymphoedema (Stewart-Treves syndrome post-mastectomy)

Metastatic Mx: Paclitaxel or Liposomal doxorubicin

Soft tissue sarcoma

Arise from mesenchymal cells

Li-Fraumeni (TP53 mutations) has the broadest and strongest association

Limited/no role for RT in retroperitoneal or intra-abdominal sarcoma

Size cut-off = <5cm

Metastatic mx, most tumours: Doxorubicin ± ifosfamide (if urgent shrinkage needed)

All subtypes and frail → consider PO cyclophosphamide/prednisolone

Alveolar soft part sarcoma (ASPS)

Aggressive soft-tissue sarcoma, high risk of local recurrence after resection → metastasis to the lungs and brain

RESISTANT to chemotherapy, including doxorubicin and ifosfamide.

Radiation significantly reduces the risk of sarcoma recurrence after resection; recommended treatment for soft-tissue sarcoma arising in an extremity.

Sunitinib has activity in locally advanced/metastatic setting

Kaposi sarcoma

·        Soft tissue vascular tumour

·        Associated with HPV8 + HIV infection

·        Need to check for mucosal and visceral involvement on scans – can lead to life threatening GI bleeds

·        Mx: HAART therapy

o   Can add in liposomal doxorubicin or paclitaxel if not enough

Chondrosarcoma

• malignant cartilage tumour; conventional type chemo-resistant.

• Surgery = only curative option, cut-off = 8cm

  • Not translocation-driven, more complex genetics. Around 50% have mutations in IDH1 and IDH2

  • Most are low-grade and occur in people >40 years.

  • Children have a worse prognosis

  • Multi-nodular, scalloped edging

• Metastatic: Pazopanib or other TKI

Giant cell tumour of the bone

·        Treatment options: en bloc excision and intralesional curettage ± adjuvant therapy in carefully selected cases

·        RT reserved for spinal lesions that can lead to cord compression.

·        Denosumab is standard treatment in unresectable or metastatic

Uterine Leiomyosarcoma

Rare, aggressive uterine mesenchymal malignancy (~1–2% of uterine cancers)

Localised Mx: Surgery. No adjuvant.

Advanced Mx: 1L - Doxorubicin or Gem/Docetaxel

2L: Trabectidin / Pazopanib

Phaechromocytoma

• Surgery = treatment of choice (after α-blockade) by a adrenal-trained surgeon.

• Surgery is also done for palliation (e.g., symptomatic catecholamine secretion, local control).

• Advanced/metastatic:

  • MIBG therapy (I-131 labelled).

  • TKIs (sunitinib, cabozantinib) show activity.

  • Cytotoxic chemo (cyclophosphamide/vincristine/dacarbazine) in aggressive disease.