Rectal Cancer. Rohit Joshi

Transcription

1 Rectal Cancer Rohit Joshi Consultant, Medical Oncology Director, Cancer Research and Clinical Trials Director, Advanced Physician Training Lyell McEwin & Modbury Hospitals Consultant, Medical Oncology Calvary Central Districts Hospital Clinical Lecturer, Discipline of Medicine, University of Adelaide

2 Cancer Commands Attention Few topics in medicine engender as much emo8onal response as the treatment of cancer. - modified from Levene, Harris, Hellman

3 Australian Stats: Incidence 2014: ~16,980 Australians will be diagnosed (9,250 in men and 7,730 in women) Commoner in men: 73.7 per 100,000 men vs 51.1 per 100,000 women Average age of diagnosis is 69.3 years Risk of bowel cancer increases with age Risk of bowel cancer before the age of 85 is 1 in 12

4 Australian Stats: Mortality 3,999 deaths (2,219 men and 1,780 women) - 9.3% of all cancer deaths in Australia Age- standardised mortality rate is 19.7 deaths per 100,000 men vs 12.7 per 100,000 women Age- standardised mortality rate for bowel cancer has decreased from 31.5 deaths per 100,000 in 1982 to 15.9 deaths per 100,000 in 2011 Risk of dying from bowel cancer before the age of 85 is 1 in 46

5 Australian Stats: Survival RelaXve survival rates between and , five- year relaxve survival increased from 48.0% to 66.2%

6 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Colorectal Cancer: Stage at Diagnosis Stage IV 19% Stage III 25% Stage 0 7% Stage I 24% Stage II 25% National Cancer Database.

7 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Colorectal Cancer: Standard Therapy Algorithm Stage Colon Rectal I (T 1 -T 2, N 0, M 0 ) Surgery only Surgery only II (T 3 -T 4, N 0, M 0 ) III (T any, N +, M 0 ) IV (T any, N any, M 1 ) Surgery ± chemotherapy Surgery à chemotherapy Chemotherapy ± surgery Chemoradiation à surgery à chemotherapy OR Surgery à chemoradiation + chemotherapy Chemotherapy ± surgery NCCN. Clinical practice guidelines in oncology: colon cancer. v

8 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Survival Rates by Stage Survival Rate I IIA IIB IIC IIIA IIIB IIIC IV Yrs From Diagnosis Edge SB, et al. AJCC cancer staging manual Data from the SEER Public Use File diagnosed in years

9 Rectal Cancer Treatment modalixes: Surgery Radiotherapy Chemo- radiotherapy Chemotherapy Cytotoxics Biologicals/Targeted therapies Best SupporXve Care

10 Chemo- Radiotherapy What? Why? When? How?

11 Treatment Overview CT- RT Complete CT- RT Surgery Chemo Follow- up Wait period

12 Chemotherapy What? Why? When? How?

13 Metastatic Process: Angiogenesis and Proliferation

14 Metastatic Process: Angiogenesis and Proliferation

15 Metastatic Process: Invasion Into Circulation

16 Metastatic Process: Invasion Into Circulation

17 Metastatic Process: Invasion Into Circulation

18 Metastatic Process: Invasion Into Circulation

19 Metastatic Process: Invasion Into Circulation

20 Metastatic Process: Invasion Into Circulation

21 Metastatic Process: Vessel Wall Adherence

22 Metastatic Process: Vessel Wall Adherence

23 Metastatic Process: Vessel Wall Adherence

24 Metastatic Process: Extravasation

25 Metastatic Process: Extravasation

26 Metastatic Process: Extravasation

27 Metastatic Process: Extravasation

28 Metastatic Process: Formation of Metastasis

29 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Stage IV CRC: Best supportive care OS (Mos) FU Median OS Irinotecan Capecitabine Oxaliplatin Cetuximab Bevacizumab Panitumumab Yr Ziv-aflibercept Regorafenib 2010

30 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Performance Status Critical factor to consider when choosing therapy Grade Criteria ECOG Performance Status [1] 0 Fully active, able to carry on all predisease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work 2 Ambulatory and capable of all self-care but unable to carry out any work activities; up and about > 50% of waking hours 3 Capable of only limited self-care; confined to bed or chair > 50% of waking hours 4 Completely disabled; cannot carry on any self-care; totally confined to bed or chair 5 Dead 1. Oken MM, et al. Am J Clin Oncol. 1982;5:

31 Choice of therapy KRAS status Disease free interval Anticipated side effects of treatment Availability/access to treatment Patient preferences Choice of Therapy Previous therapy ECOG status Patient symptoms Visceral vs non-visceral metastases Adapted from Beslija, et al. Ann Oncol 2007

32 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Characteristics Driving Decision Making Performance score Age Comorbid illnesses Extent of disease Intent of treatment (palliative vs potentially curative) Previous adjuvant therapy within 1 yr Organ function: hepatic and renal KRAS status Risks for toxicity: active CAD/CVD, proteinuria, active bleeding, nonhealed wound, allergy to mab, neuropathy, IBD, ILD, Gilberts Convenience Cost Patient preferences

33 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Access to Chemotherapy Improves Survival in mcrc Median OS (Mos) Patients With 3 Drugs (%) Grothey A, et al. J Clin Oncol. 2005;23: First-line Therapy Infusional 5-FU/LV + irinotecan Infusional 5-FU/LV + oxaliplatin Bolus 5-FU/LV + irinotecan Irinotecan + oxaliplatin Bolus 5-FU/LV LV5FU2

34 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Tumor Genomics: Intratumor Mutation Heterogeneity Substantial heterogeneity: Primary vs metastasis Across metastatic sites Within metastatic sites Gerlinger M, et al. N Engl J Med. 2012;366:

35 We need a paradigm shie a new We need a paradigm shift a new approach based on the biology of the disease approach based on the biology of the disease Premise No. 1 cancer is not a single disease Premise No. 2 cancer is not a single disease even within a given histology. The only thing ALL colorectal cancers share in common is that they arise in the organ that defines us as a species the bowel Premise No. 3 a need to develop new therapeutic approaches that take into account No. 1 and No. 2

36 The One-Size-Fits-All approach to colorectal cancer... does NOT work

37 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Colorectal Cancer With Liver Metastases Approximately 30% to 40% of patients will have liver-only metastases at time of recurrence Approximately 20% to 30% will have liver-only metastases on initial evaluation 25-30,000 patients with liver-only metastases Ohlsson B, et al. Acta Oncologica. 2003; 42: Weiss L, et al. J Pathol. 1986;150:

38 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Liver Metastases in Colorectal Cancer: Outcomes Liver Metastases Resectable 20% to 25% Nonresectable 75% to 80% Location Size Number Downsizing Survival Benefit 30% to 40% at 5 years 15% at 10 years Resectable 10% to 20%

39 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Clinical Practice*: 2-Yr OS by Hepatic Metastasectomy and R0 Resection Hepatic metastasectomy and R0 resection (n = 114) OS Estimate Hepatic metastasectomy total (n = 145) No curative hepatic metastasectomy (n = 1769) Mos *BEAT (nonrandomized study): first bevacizumab expanded access trial Okines A, et al. Br J Cancer. 2009;101:

40 Chemotherapy Medica8ons 5- Fluorouracil Capecitabine OxaliplaXn Irinotecan Bevacizumab Cetuximab Panitumumab

41 Adverse Effects We treat paxents and send them home Need to deal with adverse effects Partnership with GPs to deal with symptoms

42 Diarrhoea Chemo- radiaxon irritates the bowel 5- Fluorouracil, Capecitabine, Irinotecan Increase fluids Loperamide tablets: maximum 6 8 per day Stop chemotherapy medicaxons Hospital admission

43 Febrile Neutropenia Fever while on chemotherapy Neutrophil count of less than 1500 Need intravenous anxbioxcs urgently Nearest ED PaXent informaxon kit

44 Peripheral neuropathy OxaliplaXn Subtle inixally If lasts for more than a few days complain Reduce dose Stop OxaliplaXn

45 Diabetes Steroids pre and post chemotherapy 4 5 days of high blood sugar levels Might need insulin

46 DVT and PE PICC and InfusaPORT lines Cancer is pro- thrombogenic High suspicion Ultrasound lower limbs CTPA LWMH Clexane or Fragmin

47 Central lines

48 Bleeding Low platelet count Bevacizumab: no operaxve procedures, no dental extracxons LMWH Steroids and NSAIDs New anx- Xa agents

49 Hand Foot Syndrome Capecitabine and 5- Fluorouracil Adjuvant versus metastaxc disease Hold chemotherapy Reduce dose for future

50 Hypo- Magnesemia Cetuximab and Panitumumab Renal magnesium retenxon capacity is compromised Tablets of Magnesium Intravenous Magnesium

51 Treating the Patient With Newly Diagnosed Metastatic Colorectal Cancer clinicaloptions.com/oncology Acneiform Eruption Associated With EGFR Inhibitors Antibiotics: doxycycline Moisturizers/sunscreens Hydrocortisone acetate 1% cream Lacouture ME, et al. Support Care Cancer. 2011;19: Segaert S, et al. Ann Oncol. 2005;16:

52 Fer8lity Full dose chemo- radiaxon to pelvis sterile Semen preservaxon upfront Issues with occasional paxent

53 Clinical Trials Advancement of Science Treatment opxons for paxents, who can never get access otherwise Everything is monitored by mulxple people, nothing is missed Cost of therapy

54 Learning Objec8ves Suspicion and Diagnosis Referral pathways Reduce mortality, prevenxon and screening Outcomes of treatment PaXent support while on treatment

55 Outcomes of Treatment Surgery: ResecXon of primary tumour and possible mets Chemo- radiotherapy: neoadjuvant therapy Chemotherapy: adjuvant or metastaxc treatment Leiers to GP and other treaxng doctors MulX- disciplinary MeeXng recommendaxons Shared care pathways Discharge plan from a service

56 Pa8ent Support during Treatment Nursing support Chemotherapy Day Centre Emergency presentaxons GP appointments PalliaXve Care PATs Counseling services Support groups: CanTeen, Cancer Council, Jodi Lee FoundaXon, Cancer Voices

57 Colorectal cancer: The hope con8nues

58 Thank you for being a part of the experience