Malignant Bowel Obstruction Gordon Jayson Christie Hospital and
Malignant Bowel Obstruction Gordon Jayson Christie Hospital and University of Manchester September 2019
New Patients Ovarian cancer presentation - Typically late 50 s-60 s - Few weeks/months - Abdo distension, discomfort - Change in bowels Differential diagnosis - (IBS) - CRC - Ovarian Cancer - Ca 125 (NICE)
Ovarian Cancer and Malignant Bowel Obstruction Symptoms and Signs • Nausea, vomiting • Reflux • Abdominal distension, pain • Borborygmi • Constipation or change in bowels • Progressive symptoms over 2 m. <50% of ovarian cancer Differential or Additional Diagnosis • Ascites Morgan ESMO Open 2019
Abdominal Radiographs in Malignant Bowel Obstruction
Initial Management of Malignant Bowel Obstruction Nausea and Vomiting • IV fluids • NBM • Cyclizine (or metoclopramide) • Steroids • NG Tube • Levomepromazine • SC Drivers Pain • Constant: Opiates • Colicky: anti-spasmodics Nutrition • Liquids or NBM • Low residue diet Constipation • Laxatives (softeners) • Enemas Abdominal Distension • Ascites
After a Few Days of Malignant Bowel Obstruction Radiological Evaluation Surgical Advice Nutritional Support Physiotherapy NGT vs Venting gastrostomy Psychological Chemotherapy Multi-site obstruction Scans under-estimate disease Surgery usually not indicated Stents not helpful
Institution of Total Parenteral Nutrition (TPN) Most patients have not eaten normally for weeks • Involve dieticians early • multi-vitamins • TPN (refeeding syndrome) Collaboration with Salford Royal Intestinal Failure Team • Complete referral forms • Make referral when stable • Discharge for Home TPN (HPN) now in 2 weeks Is this the answer to MBO? • Restoration of independence • Loss of meal-times • Loss of family interaction • Loss of control • Burden of treatment protocol • Consideration of when to stop HPN Sowerbutts, Cochrane, 2018
Malignant Bowel Obstruction: Outcomes (2003 -11) OS (days) N Age 129 patients 61 yrs PS 2 -4 59% Multisite disease 74% Surgery 24% 152 Chemotherapy 50% 124 BSC 26% 45 Chemo-naive 23% 124 Pt-sensitive 29% 188 Pt-resistant 53% 168 Dean Future Oncol 2017
Maintenance Therapies
Maintenance Therapy in 1 st Line Management of Ovarian Cancer Boost Trial 15 vs 30 m Bevacizumab PAOLA: PAOLA Bev +/olaparib Surgery Chemotherapy Olaparib in g. BRCAm GOG 3005 Velaparib co-admin Moore NEJM 2018 PRIMA Niraparib BRCAwt/m 391 pts: HGSO/EC stage III/IV, PS 0/1 CR/PR after Pt, 2: 1 2 yrs olaparib
SOLO 1: Olaparib in 1 st line maintenance of BRCAm-ovarian cancer SOLO 1 PFS FIGO III/IV HGS/EOC, PPC, FTC g/s. BRCAm, PS 0/1 Surgery, Pt-chemo CR/PR Olaparib 300 mg bd N=260 PD or 2 years Placebo N=131 Median follow up 41 months Olaparib progression free at 36 m: 60. 4% Placebo progression free at 36 m: 26. 9% HR 0. 3; p<0. 001 Nausea, Tiredness, Anaemia, Diarrhoea Constipation, Arthralgia, Neutropenia.
Maintenance Therapy in 1 st Line Management of Ovarian Cancer Boost Trial 15 vs 30 m Bevacizumab PAOLA: PAOLA Bev +/olaparib Surgery Chemotherapy Olaparib in g. BRCAm GOG 3005 Velaparib co-admin Moore NEJM 2018 PRIMA Niraparib BRCAwt/m 391 pts: HGSO/EC stage III/IV, PS 0/1 CR/PR after Pt, 2: 1 2 yrs olaparib
Presence of T cells More (maintenance) is better… or is it? TIL therapy ✓ IMa. GYN 050: Bev +/- Atezo VEGFi Neo antigens ✘ PD-(L)1: Avelumab (Javelin) PARPi DUO-O Durvelumab Bevacizumab Olaparib PD-1/PD-L 1 ✓ ATHENA: Rucaparib, nivolumab JAVELIN 100 PARP: Avelumab, talezaporib
How do we choose between maintenance therapies? Ov Ca CRC % change from pre-treatment p. Tie 2 response biomarker for VEGFi Chemo-bev % PFS • 75% vascular RR in ov ca/ CRC • Vascular response is >30% reduction in Tie 2 in 9 wks • Vascular resistance/progression is >50% increase in Tie 2 above nadir Aim To qualify Tie 2 for clinical decision making for bevacizumab in ovarian cancer. Backen CCR 2014; Zhou BJC 2016; Jayson Nat Comm 2018
Current Maintenance Strategies in Ovarian Cancer 1 st line Olaparib BRCAm HGS/E OC CR/PR 1 st line bevacizumab IIIc/IV HGSOC Bulk disease or and 2 nd line+ Niraparib BRCAm/wt Pt-sens HGSOC or 3 rd line+ Olaparib BRCAm Pt-sens HGSOC Use-reuse proven PAOLA trial reported as positive - Bevacizumab and olaparib Needed for Pt-resistant disease MOLTO CEBOC
Conclusions • Ovarian cancer is becoming a chronic disease • Two classes of maintenance therapy • • PARPi- BRCAm population and platinum-sensitive VEGFi: effective irrespective of platinum-sensitivity Both together Immune therapy disappointing • Bowel obstruction… the final frontier!
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