Palliative care

Section: Surgical Oncology Curriculum: Curriculum, page 68

Esophageal Cancer

• 75% of EC are unresectable on presentation
• Indications for palliation include patient wishes, comorbid disease, and distant mets or M1 nodal mets, T4 airway, aorta, or cardiac invasion, peritoneal disease
• Palliative -median survival of 8 months
• Little evidence to show any single or combo of treatment changes survival
• Symptoms
  • Dysphagia
  • Vomiting
  • Bleeding
  • Reflux
  • Anorexia
  • Pain
  • weight loss
  • hoarseness
  • aero-digestive fistula
• Treatment for dysphagia
  • Endoscopically or radiologically placed self-expanding metal stents
    • Risks include malposition, incomplete expansion, migration, perforation, bleeding, tumour ingrowth, food bolus obstruction, reflux, pressure necrosis, stent fracture.
    • Not suitable for cervical tumour
  • Laser (Nd:YAG) - mainly used to deal with ingrowth around stent, non-circumferential tumours, or recurrence after surgery
    • APC - now largely replaced laser
    • Photodynamic therapy - photosensitiser (haematoporphyrin derivative) is injected IV 3-4 days before, then laser delivered to cancer, activating it to create reactive oxygen species which causes tissue destruction. SE include skin sensitivity for 6 weeks
  • Ethanol injection - safe and cheap
  • Radiotherapy
    • External beam causes significant side effects (stricture, lung fibrosis, fistula) and only about 40% effective
    • Brachytherapy using caesium down a flexible NGT effective - less side effects and better long-term relief of dysphagia than stents
  • Chemotherapy - no good evidence to support its use
• Aero-digestive fistula - difficult to treat and short life expectancy - best treated with stenting
• RLN palsy - treat with Teflon injection
• Bleeding - treat with laser, adrenaline injection, diathermy, or EBRT

Stomach Cancer

• Median survival 6-8 months
• Indications for palliation include patient wishes, comorbid disease, distant mets or M1 nodal disease, peritoneal disease
• Chemo improves survival compared to best supportive care
• Palliative surgery or stenting can relieve symptoms
• Cardia tumours treated like esophageal cancers (Siewert)
• Symptoms of gastric body and antrum cancers include bleeding and gastric outlet obstruction
• Chemotherapy (ECF) is recommended treatment - improves survival and relieves symptoms, but often worsens general QOL
• Gastric outlet obstruction can be treated with subtotal or total gastrectomy, gastrojejunostomy, and stenting
• Bleeding can be treated with gastrectomy, laser, APC, or RT

Breast Cancer

• 6-10% BC patients present with metastatic disease
• Overall 5Y 26%, median survival 2 years
• Most patients do not need primary excised as they will not live long enough for local disease to be a problem. But patients with mets responding to systemic treatment can consider surgery for local control. RT not indicated unless in bulky disease with surgical margins positive.
• Bone mets most common - can treat with bisphosphonates as fracture prevention, or for treatment of bone pain. Other treatments include prophylactic or therapeutic fracture fixation and radiotherapy for pain or post stabilisation surgery

Melanoma

• Isolated limb perfusion or infusion with melphalan (L-phenylalanine mustard)
• Radiotherapy - relieve symptoms in patients with mets to bone, brain, soft tissue, liver, adrenal
• Single agent chemo (fotemustine, dacarbazine, temozolomide) can be used for palliation of patients with distant mets. Interferon-α and IL-2 can also be used, but no improvement in survival, and no benefit in adding it to chemo
• Patients with resectable distant mets have prolonged survival after resection - so limited mets to skin, distant nodes, lung, adrenal, liver, GI tract, brain should be resected
• Brain mets with poor prognosis (multiple, extracranial disease, poor performance status) can be treated with whole-brain RT, chemo, and steroids

Colorectal Cancer

• Locally advanced tumour can be resected if possible. If not bypass R-sided cancers and defunction L sided ones.
• Liver mets - consider resection
• Lung mets - small number of patients can be resected
• Palliative chemo - FOLFOX, FOLFIRI, Capecitabine
• Avastin (Bevacizumab) – angiogenesis inhibitor

Thyroid Cancer

• Surgery if symptomatic recurrent locoregional disease, or aerodigestive tract compromise
• Lung mets - radioactive iodine
• Bone or brain mets - resection, RAI, RT plus steroids
• Unresectable neck disease - consider RT
• Chemo - no good evidence for it

Pancreatic Cancer

• Jaundice - ERCP best, then PTC if lesion proximal, then surgical bypass. If life expectancy >6m, surgery may be better as stents may block. Metal stents better than plastic ones (larger diameter so block less)
• Gastric outlet obstruction occur in 20% - endoscopic stenting if life expectancy short, surgical bypass if prolonged - gastrojejunostomy best and can be done laparoscopically
• Pain - can consider chemical splanchnicectomy
• Pruritus - cause unclear, but cholestasis may lead to liver to produce pruritogenic substances (? endogenous opioid).
  • Treatment include sedatives eg benzodiazepines, ondansetron, SSRI, naloxone.
  • Antihistamines not effective (except to act as sedative).
  • Cholestyramine (non-absorbable resin that binds pruritogen excreted in bile) can be tried but probably doesn’t work that well, not surprising as bile not reaching gut.

PNETs - for non-functioning metastatic cancers no role for debulking, but if hormonal excess, liver mets cytoreductive surgery may be worthwhile if >90% tumour can be removed. Other potential options include somatostatin, interferon, hepatic artery embolization, RFA, chemo

Liver Cancer (HCC)

• Traditional chemo little role
• Antiangiogenic treatment eg Sorafenib which inhibits VEGF receptors

Colorectal Liver Mets

• FOLFOX/FOLFIRI - 40-50% response rate
• Role of RFA in addition to chemo for unresectable mets unclear

Cholangiocarcinoma

• Hilar
  • Elderly comorbid patients - support care only
  • PTC - not used for all jaundiced patients as significant morbidity (infection) so use in intractable pruritus or recurrent cholangitis
  • Patients found to be unresectable at laparotomy - surgical intrahepatic biliary-enteric bypass (often to segment 3 or R anterior or posterior sectoral duct)
  • Limited role for RT - no survival benefit
  • Chemo (5FU based) - some evidence for short term improvements in survival and QOL
• Distal
  • ERCP stenting or surgical bypass if unresectability found at surgery
• Intrahepatic
  • No evidence to support use of chemo or RT for palliation

Gallbladder Cancer

• Percutaneous or endoscopic drainage preferred

Cachexia

• Due to hypercatabolic state
  • Excess loss of lean body mass (skeletal – sarcopenia)
    • Targets myosin heavy chain
    • Cytokines
    • ?Proteolysis-inducing factor
    • ?Lipid mobilising factor – loss of fat also occurs but less dominant
    • ?ATP-ubiquitin-proteasome pathway – final common pathway?
      • Proteasome inhibitor – bortezomib – one trial so far didn’t work
    • Cancer treatment
      • Androgen deprivation therapy in prostate cancer = increased skeletal muscle loss
  • Increased resting energy expenditure (cytokines – TNFα, IL-1β, IL-6)
  • But so far TNFα inhibitors haven’t helped
• Loss of appetite
  • Demonstrated that there is often a significantly lower caloric intake
  • Chemotherapy may contribute – altered taste, nausea, vomiting
  • Proinflammatory cytokines
  • Direct tumor effect
• Weight loss
  • 5% weight loss – independent poor prognostic factor
• Cachexia may be a direct cause of death
• Often have hyperglycaemia, hypertriglyceridemia & exaggerated insulin response to glucose
• Reduced LDL production & reduced lipolysis & reduced activity of lipoprotein lipase