ON13 Colorectal cancer

Choose the incorrect epidemiology statement about colorectal cancer.

NZ stats: - Eight New Zealander’s diagnosed each day​ - [blank_start]Three[blank_end] New Zealander’s die from bowel cancer each day​ - [blank_start]2nd highest[blank_end] cause of cancer death in New Zealand​ - One of the highest rates in the [blank_start]world[blank_end] ​ - Rates for [blank_start]women[blank_end] are highest in world ​ - Less frequent in [blank_start]Maori[blank_end] vs. non-Maori

Risk factors for colorectal cancer: [blank_start]Male[blank_end] sex​ Age​ (older) History of colorectal cancer, [blank_start]polyps, T2DM, IBD​[blank_end] Inherited factors (e.g. familial adenomatous polyposis, [blank_start]family history[blank_end])​ Lifestyle factors​ Diet ([blank_start]red[blank_end] meat, processed food, high fat, low fibre)​ Physical [blank_start]inactivity[blank_end]​ Long term [blank_start]smoking[blank_end]​ Excessive [blank_start]alcohol[blank_end]​ Obesity

Protective Factors​: Some evidence [blank_start]NSAIDs / Aspirin[blank_end] use (13-28% RRR)​ [blank_start]Postmenopausal[blank_end] hormone use (RRR 35%)​ Healthy BMI, physical [blank_start]activity[blank_end], smoking [blank_start]cessation[blank_end]​ Fibre, fruits, vegetables, reduced meat consumption​ [blank_start]Calcium and vitamin D[blank_end] supplementation​

Screening usually starts at age 50​. Decreases mortality through early detection​. Methods:​ [blank_start]Colonoscopy[blank_end] (every 10 years post-50)​ Flexible [blank_start]sigmoidoscopy[blank_end] (every 5 years)​ CT scan (every 5 years)​ Double contrast [blank_start]barium enema[blank_end] (every 5 years)​ Fecal occult blood tests ([blank_start]annually[blank_end])​

Which of these is not a symptom of bowel cancer?

Diagnosis: History and physical exam​ Colonoscopy [blank_start]or[blank_end] sigmoidoscopy​ [blank_start]Biopsy[blank_end] (to confirm presence of cancer)​ [blank_start]CT[blank_end] scanning (search for metastases)​ Baseline [blank_start]labs[blank_end] (CBC, platelet, liver panel, renal panel, CEA, iron studies)​ Pathological staging after tumor resection ([blank_start]TNM[blank_end])​ Gene mutation testing (?)​

Staging: Stage 1 - tumour size T1 (no deeper than [blank_start]submucosa[blank_end]) and T2 ([blank_start]not all the way through muscularis[blank_end]) Stage 2 - T3 ([blank_start]through[blank_end] muscularis) Stage 3 - N1 ([blank_start]1-3[blank_end] lymph nodes involved), N2 ([blank_start]>4[blank_end] lymph nodes involved) Stage 4 - M - [blank_start]distant[blank_end] metastases.

Clinical factors associated with poor prognosis:​ Bowel [blank_start]obstruction or perforation​[blank_end] High preoperative [blank_start]CEA​[blank_end] Distant [blank_start]metastases[blank_end]​ Location of tumor in [blank_start]rectal or rectosigmoid[blank_end] area​ Molecular markers (KRAS mutations MSI, BRAF mutations)​

Treatment: Need to consider stage, performance status, patient preferences, comorbidities, age. Curability depends on tumor stage​. General approach:​ [blank_start]Surgical resection[blank_end] of primary tumor is 1st line therapy (Stage 1, 2, 3)​ Removal of tumor plus [blank_start]5cm[blank_end] of tumor free bowel and regional [blank_start]lymph nodes[blank_end] for cure​ Adjuvant [blank_start]chemotherapy and/or radiation[blank_end] can be given to eliminate residual micrometastases ​ if it's metastases (Stage 4)​? Classified as resectable, potentially resectable, or unresectable​ [blank_start]Systemic chemotherapy[blank_end] is mainstay, radiation may be used for palliative purposes​

Adjuvant Systemic Chemotherapy​: Goal: reduce risk of recurrence and overall mortality in Stage [blank_start]III[blank_end]​. (Little to no benefit from Stage [blank_start]II[blank_end], no benefit in Stage [blank_start]1[blank_end]​.) Duration: [blank_start]6[blank_end] months​ Choice of regimen based on toxicity and convenience​. Typically based on [blank_start]Fluorouracil or Capecitabine[blank_end] (both with [blank_start]oxaliplatin[blank_end])​.

Leucovorin(Folinic acid), fluorouracil and oxaliplatin aka FOLFOX side effects: - neutropenia, therefore [blank_start]infections[blank_end] - anaemia, therefore breathlessness and [blank_start]weakness[blank_end] - potentially reversible [blank_start]peripheral[blank_end] neuropathy - nausea - diarrhoea - muscositis - rarely heart problems CAPOX (capecitabine and oxaliplatin) side effects: - neutropenia, therefore infections - anaemia, therefore breathlessness and weakness - potentially reversible peripheral [blank_start]neuropathy[blank_end] - nausea - diarrhoea OR [blank_start]constipation[blank_end] - muscositis - [blank_start]palmar-plantar[blank_end] syndrome - rarely tinnitus, heart problems,

Rectal Cancer​ - Poorer outcomes. ​Difficult to [blank_start]resect[blank_end], propensity for [blank_start]recurrence[blank_end]. - Most patients with Stage II or III should receive [blank_start]combined[blank_end] radiation and chemotherapy [blank_start]peri[blank_end]operatively ​ - [blank_start]Neoadjuvant[blank_end] chemotherapy and radiation for Stage II or III​ - Adjuvant for 6 months post-surgery​ - Same regimens as indicated or colorectal (e.g. FOLFOX or CapeOx)​

Colorectal – Metastatic Disease​: - If resectable, surgery is indicated (most commonly [blank_start]liver and lung[blank_end])​. Neoadjuvant [blank_start]and[blank_end] adjuvant chemotherapy​ for patients with metastatic disease [blank_start]isolated[blank_end] to liver or lung​. FOLFOX, FOLFIRI, FOLFOXIRI, CapOx​. - Unresectable​ - Chemotherapy (e.g. FOLFOX, CapOx, FOLFIRI)​ only. Goal is to control [blank_start]growth[blank_end] and prolong survival.​ Role for [blank_start]targeted[blank_end] therapy (bevacizumab) [inhibits VEGF]​ & EGFR inibitors (cetuximab, panitumumab) [for patients with wild-type RAS tumors)​

A note about Irinotecan… ​ Evidence exists for metastatic disease​! Improved overall [blank_start]survival[blank_end] vs. 5FU/LV alone​ :-) Combination with 5FU/LV +/- oxaliplatin may improve [blank_start]resectability[blank_end] of metastases and improve patient survival . Must monitor for [blank_start]diarrhea and neutropenia[blank_end]​. Data in adjuvant setting (non-metastatic disease) lacking​...

Oral Capecitabine: May be commonly seen in community pharmacy​. Caution in: [blank_start]CVD, diabetes,[blank_end] electrolyte disturbance, [blank_start]skin[blank_end] conditions. Avoid in [blank_start]severe hepatic[blank_end] impairment​. Dose reductions if CrCl [blank_start]< 50[blank_end]ml/min, avoid [blank_start]<30[blank_end]ml/min ​. Contraceptive advice [blank_start]required[blank_end] for child-bearing aged females​. Potential ADRs: ​ hand-foot syndrome, diarrhea, [blank_start]arrhythmias[blank_end] (rare), [blank_start]severe[blank_end] skin conditions (very rare)​