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  • Pancreatic Ductal Adenocarcinoma

    Razvan Popescu Tumor Center Aarau

    Switzerland

  • Teaching aims

    • Discuss role of palliative care in PDAC • Metastatic or locally advanced irresectable

    disease – First line Therapies – Second line Therapies – Novel approaches

    • (Borderline) Resectable disease

  • Epidemiology

    • In Europe fourth most common fatal cancer in men (after lung, colorectal, and prostate) and women (after breast, colorectal and lung)

    • Death due to PC increasing, projected to become second most common fatal cancer by 2030

    • Life expectancy overall of 5% at 5 years

  • Importance of Supportive and Palliative Care

    Median Survival of Patients With Pancreatic Cancer

    • Localized/ Resectable 15 - 24 months 10%

    • Locally Advanced 6 - 15 months 30%

    • Metastatic/ Advanced 3 - 12 months 60%

  • Pancreatic cancer symptom burden • Asthenia 85% • Weight loss • Anorexia • Abdominal / epigastric pain • Dark urine • Jaundice • Nausea • Back pain • Diarrhea • Vomiting • Steatorrhea • Abdominal fullness • Thrombophlebitis 2-3%

  • Recent guidelines call for early palliative care as a new standard

    Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline 2016: “Patients should have full assessment of symptoms, psychological status, and social supports and should receive palliative care early”

    www.asco.org/guidelines/PCPC

  • Supportive and Palliative Care

    • Start supportive and palliative care as soon as diagnosis is suspected – pancreatic cancer is an EMERGENCY

    • Assess symptoms and their speed of development • Consider pain, weight loss, exocrine pancreatic

    insufficiency, jaundice*, delayed gastric emptying*, VTE, depression, etc.

    * Biliary obstruction: endoscopic stent placement * Duodenal obstruction: endoscopic metal stent placement

  • Many patients assume they can be cured

    with palliative measures

    • 1193 patients participating in the Cancer Care Outcomes Research

    and Surveillance (CanCORS) study receiving chemotherapy for

    stage IV lung or colorectal cancers

    • 69% lung and 81% colorectal cancer patients did not understand that

    their treatment was not at all likely to cure their cancer.

    • Inaccurate beliefs were higher among patients who rated their

    communication with physicians very favorably !

    • Educational level, functional status, and the patient's role in decision

    making were not associated with such inaccurate beliefs about

    chemotherapy

    – Weeks JC, et al. Patients' expectations about effects of chemotherapy for

    advanced cancer. N Engl J Med. 2012 Oct 25;367(17):1616-25.

  • • Benefits of OUTPATIENT concurrent palliative care: – Avoided admissions and readmissions, increase referral to

    hospice, – Better communication and satisfaction – Equal or lowered costs to the health system – Equal or better symptom management – Equal or improved quality of life – Equal or LONGER survival – Not a single trial showed harm, added cost, or burden

    Recent Randomized Trials document Impact of EARLY Palliative Care

  • How about systematic early palliative care integration in pancreatic cancer?

    • Many principles can be extrapolated from other trials

    • Metastatic pancreatic cancer patients were randomized between early vs. on-demand palliative care in an Early Palliative Care Italian Study Group (EPCISG) multicenter trial.

    • The early palliative care group had significantly improved QoL, there was no difference in survival

    Maltoni M et al, Eur J Cancer. 2016 Sep;65:61-8. doi: 10.1016/j.ejca.2016.06.007

  • Pancreatic cancer symptoms

    • Pain – Assess at every visit including response to analgesics – May be neuropathic and require co-analgesics – RT or Celiac Plexus Block

    • VTE – Four- to seven-fold higher in pancreatic cancer than in other

    common adenocarcinomas, risk highest in first months after diagnosis and increased by chemotherapy

    – Prophylaxis with LMWH reduces VTE but does not improve OS in outpatients- those with previous VT/E - lifelong LMWH

    • Anxiety and Depression – 1/3 -2/3 of patients – Use validated instruments or “Are you depressed?” – Duloxetine or Venlafaxine co-treat neuropathic pain

  • GI problems in Pancreatic Ca Patients

    • Anorexia • Early satiety • Weight loss • Fatigue, weakness • Nausea • Constipation • Ascites • Malabsorption

    • Cachexia

    • Early involvement of nutritionist / dietitian

    • Assess nutritional intake • Assess malabsorption • Supplement pancreatic enzymes • Treat reversible causes like

    constipation, ascites, delayed gastric emptying /gastroparesis

  • GI Problems - Transit

    • Constipation – can be due to opioid intake, peritoneal carcinomatosis, ascites,

    delayed gastric emptying

    • Ascites – May be caused by peritoneal carcinomatosis or portal vein

    thrombosis / obstruction – Patients with portal hypertension may respond to diuretics – Paracentesis, if repeatedly necessary insert long term catheter

    • Delayed gastric emptying – often without obstruction, gastrographin image series may help

    discriminate – If obstruction is not predominant, prokinetics may help – NG tube in recurrently vomiting patients, ? PEG / PEJ tube

  • Jaundice from biliary tree obstruction

    • Leads to pruritus, risk of cholangitis • Best treatment (least invasive) is placement of a stent

    – preferably a metal stent if permanent stent is intended (fewer recurrent obstructions)

    – Plastic stents are cheaper and can be easier removed or exchanged

    – If the tumor is potentially removable, speak to the surgeon as to their preferences re plastic vs. metal stent

    – If endoscopic placement fails percutaneous placement may be an option

    – If cholangitis occurs, emergency antibiotics and stent change may be life saving

    • Surgical bypass is an option

  • Exocrine pancreatic insufficiency

    • Leads to maldigestion, fat malabsorption, and steatorrhea

    • Typically symptoms include abdominal cramping, flatulence, urgency to defecate, weight loss and steatorrhea (greasy, foul-smelling, soft stools that are difficult to flush- may be less prominent if patients limit fat ingestion)

    • Treat patients empirically with adequate doses of oral pancreatic enzyme replacements – best ingested with meals – 30’000 IU Lipase

    – Microencapsulated variants better with gastric acid secretion – if not efficacious, consider PPI

    • Frequent smaller meals may be preferable

  • Anorexia - Cachexia

    • Weight loss and Anorexia – loss of appetite – is common and multifactorial, but in many cases reversible – Dysgeusia, xerostomia – Poor appetite – Poor GI transit/ motility or absorption – Early satietey (ascites, hepatomegaly) – Weight loss > 5% correlates with worse mortality

    • Cachexia is characterized by – Excessive loss of lean body (skeletal muscle) mass – Cytokine activation and chronic inflammatory response – Increased basal metabolic rate / ‘hypermetabolic state’ – Far more than poor caloric intake – Correlates with poor prognosis, directly linked to severity

  • Cachexia management

    • Established Cachexia syndrome difficult to manage – supportive care, psychological assistance, discouraging relatives to force feed

    • Pre-cachexia more likely to respond to therapy – ideally managed by teams including pall care

    specialists, psychologists and nutritionalists – Small meals, supplements – Physical exercise – Trials of dexamethasone or

    medroxyprogesteroneacetate (short term, VTE risk!) may be warranted

    – Clinical trial participation warranted

  • Locally advanced inoperable / metastatic Pancreatic Cancer

  • Predicting Prognosis in advanced PDAC The MSKCC Prognostic Score (MPS)

    • A modification of the Glasgow Prognostic Score (CRP >10 and Albumin < 3.5 g/dl)

    • Neutrophil / Lymphocyte Ratio (NLR) >4 and Albumin < 4 g/dl) get each 1 point

    Andrew Cheung Yang, Abstract 4105, ASCO 2017

  • Advanced inoperable/ metastatic Pancreatic Cancer

    • Gemcitabine has been standard of care for over a decade – various trials adding other cytotoxics have shown a (marginal) survival benefit with increased toxicity*

    • Two recent trials however showed clear superiority of novel regimens: – FOLFIRINOX in the French PRODIGE 4 / ACCORD 11

    – Gem/ nab-paclitaxel in MPACT Trial

    *Ciliberto D et al. Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomised trials. Eur J Cancer 2013; 49: 593–603

  • Gemcitabine Established as Treatment

    Standard for PDAC over 20 Years Ago

    • First-line gemcitabine vs 5-

    FU in advanced pancreatic

    cancer

    – Median OS: 5.7 vs 4.4 mos

    (P = .0025); 1-yr OS: 18% vs 2%