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Challenges and Opportunities in Metastatic Gastric Cancer

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Challenges and Opportunities in Metastatic Gastric Cancer

  1. 1. www.i3Health.com Clinical Tools and Resources for Self-Study and Patient Education Gastric Cancer Reference Guide The clinical tools and resources contained herein are provided as educational adjuncts to the CME/CE-approved online activity Challenges and Opportunities in Metastatic Gastric Cancer. To access the activity and earn CME/CE credit, visit: www.i3Health.com/gastric-cancer Contents I. TNM Staging of Gastric Tumors.........................................................................................................2 II. General Staging of Gastric Cancer....................................................................................................3 III. Gastric Cancer: General Treatment..................................................................................................5 IV. Gastric Cancer: Components of Treatment .....................................................................................6 V. Systemic Therapy for Gastric Cancer: Adverse Events .....................................................................7 VI. Gastrectomy: Patient Guidelines for Adverse Events ....................................................................10 VII. Post-Gastrectomy Eating Guidelines ............................................................................................12
  2. 2. 089GC Reference Guide | Page 2 of 12 www.i3Health.com I. TNM STAGING OF GASTRIC TUMORS TNM Clinical Classifications Tumor TX Primary tumor cannot be evaluated T0 There is no evidence of primary tumor in the stomach Tis Carcinoma in situ. Cancer is found only in cells on the epithelium (the surface of the inner lining of the stomach) and has not spread to any other layers of the stomach T1 Tumor has grown into lamina propria, muscularis mucosae, or submucosa (inner layers of the wall of the stomach) T1a Tumor has grown into the lamina propria or muscularis mucosae T1b Tumor has grown into the submucosa T2 Tumor has grown into the muscularis propria (muscle layer of the stomach) T3 Tumor has grown through all of the layers of the muscle into the connective tissue outside the stomach, but it has not grown into the peritoneal lining (the lining of the abdomen) or into the serosa T4 Tumor has grown through all of the layers of the muscle into the connective tissue outside the stomach and into the peritoneal lining, serosa, or organs surrounding the stomach T4a Tumor has grown into the serosa T4b Tumor has grown into organs surrounding the stomach Node NX Regional lymph nodes cannot be evaluated N0 Cancer has not spread to the regional lymph nodes N1 Cancer has spread to 1-2 regional lymph nodes N2 Cancer has spread to 3-6 regional lymph nodes N3 Cancer has spread to ≥7 regional lymph nodes N3a Cancer has spread to 7-15 regional lymph nodes N3b Cancer has spread to ≥16 regional lymph nodes Metastasis MX Distant metastasis (spread to other sites in the body) cannot be evaluated M0 No metastasis M1 Metastasis American Society of Clinical Oncology (2019). Stomach cancer: stages. Available at: https://www.cancer.net/cancer-types/stomach- cancer/stages
  3. 3. 089GC Reference Guide | Page 3 of 12 www.i3Health.com II. GENERAL STAGING OF GASTRIC CANCER Cancer Stage Grouping Stage Description 0 Carcinoma in situ (Tis, N0, M0) IA The cancer has grown into the inner layer of the stomach wall with no spread to lymph nodes or other organs (T1, N0, M0) IB The cancer satisfies either of the following criteria: • Growth into the inner layers of the stomach wall with spread to 1-2 lymph nodes but not elsewhere (T1, N1, M0) • Growth into the outer muscular layers of the stomach wall without spread to lymph nodes or other organs (T2, N0, M0) IIA The cancer satisfies any of the following criteria: • Growth into the inner layer of the stomach wall with spread to 3-6 lymph nodes but not elsewhere (T1, N2, M0) • Growth into the outer muscular layers of the stomach wall with spread to 1-2 lymph nodes but not elsewhere (T2, N1, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach without growth into the peritoneal lining or serosa or spread to lymph nodes or surrounding organs (T3, N0, M0) IIB The cancer satisfies any of the following criteria: • Growth into the inner layers of the stomach wall with spread to 7-15 lymph nodes but not elsewhere (T1, N3a, M0) • Invasion of the outer muscular layers of the stomach wall and spread to 3-6 lymph nodes but not elsewhere (T2, N2, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach but not into the peritoneal lining or serosa; spread to 1-2 lymph nodes but not elsewhere (T3, N1, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach and into the peritoneal lining or serosa without spread to lymph nodes or surrounding organs (T4a, N0, M0) IIIA The cancer satisfies any of the following criteria: • Growth into the outer muscular layers of the stomach wall with spread to 7-15 lymph nodes but not to other organs (T2, N3a, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach but not into the peritoneal lining or serosa; spread to 3-6 lymph nodes but not to other organs (T3, N2, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach and into the peritoneal lining or serosa; spread to 1-2 lymph nodes but not to other organs (T4a, N1, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach and into nearby organs or structures without spread to lymph nodes or distant sites (T4b, N0, M0)
  4. 4. 089GC Reference Guide | Page 4 of 12 www.i3Health.com Cancer Stage Grouping (cont.) Stage Description IIIB The cancer satisfies any of the following criteria: • Growth into the inner layer of the stomach wall or the outer muscular layers of the stomach wall with spread to ≥16 lymph nodes but not to distant sites (T1 or T2, N3b, M0) • Growth through all layers of the muscle into the connective tissue outside the stomach but not into the peritoneal lining or serosa; spread to 7-15 lymph nodes but no invasion of surrounding organs (T3, N3a, M0) • Growth through all layers of the muscle into connective tissue outside the stomach and into the peritoneal lining or serosa; spread to 7-15 lymph nodes but not elsewhere (T4a, N3a, M0) • Growth through all of the layers of the muscle into the connective tissue outside the stomach and into nearby organs or structures, with or without spread to 1-6 lymph nodes; no spread to distant sites (T4b, N1 or N2, M0) IIIC The cancer satisfies either of the following criteria: • Growth through all layers of the muscle into the connective tissue outside the stomach and possibly into the peritoneal lining or serosa; spread to ≥16 lymph nodes but not to distant sites (T3 or T4a, N3b, M0) • Growth through all of the layers of the muscle into the connective tissue outside of the stomach and into nearby organs or structures; spread to ≥7 lymph nodes but not to distant sites (T4b, N3a or N3b, M0) IV A cancer of any size that has spread to distant sites in addition to the area surrounding the stomach American Society of Clinical Oncology (2019). Stomach cancer: stages. Available at: https://www.cancer.net/cancer-types/stomach- cancer/stages
  5. 5. 089GC Reference Guide | Page 5 of 12 www.i3Health.com III. GASTRIC CANCER: GENERAL TREATMENT Treatment by Stage Stage 0 Endoscopic resection Stage IA Cancer removal by total or subtotal gastrectomy Stage IB Cancer removal by total or subtotal gastrectomy Stage II-III • Surgery to remove all or part of the stomach, omentum, and nearby lymph nodes • Chemotherapy or chemoradiation may be given before, after, or both before and after surgery Stage IV • Surgery such as a gastric bypass or subtotal gastrectomy, chemotherapy, or radiotherapy can be used to try to keep the cancer under control and help relieve symptoms • Targeted therapy American Cancer Society (2019). Treatment choices by type and stage of stomach cancer. Available at: https://www.cancer.org/cancer/stomach-cancer/treating/by-stage.html
  6. 6. 089GC Reference Guide | Page 6 of 12 www.i3Health.com IV. GASTRIC CANCER: COMPONENTS OF TREATMENT Gastric Cancer Treatment Treatment Description Surgery • Partial or total gastrectomy o Can be used in conjunction with chemotherapy or radiotherapy Radiotherapy • Can be used in conjunction with surgery and/or chemotherapy Chemotherapy • Can be used in conjunction with surgery and/or radiotherapy • Chemotherapy drugs used for gastric cancer: o Cisplatin (Platinol® ) o Fluorouracil (Adrucil® ) o Capecitabine (Xeloda® ) o Docetaxel (Docefrez®, Taxotere® ) o Epirubicin (Ellence® ) o Irinotecan (Camptosar® , Onivyde® ) o Oxaliplatin (Eloxatin®) o Paclitaxel (Taxol® , Onxal® ) Targeted Therapy • Treatment that targets specific genes, proteins, or the tissue environment that contributes to cancer growth and survival • Human epidermal growth factor receptor 2 (HER2)-targeted therapy for HER2- positive (HER2+) cancer o Treated with trastuzumab (Herceptin® ) plus chemotherapy in later-stage cancer • Antiangiogenesis therapy focuses on stopping the process of making new blood vessels. Because a tumor needs the nutrients delivered by blood vessels to grow and spread, the goal of antiangiogenesis therapies is to “starve” the tumor o For patients whose tumors has grown while receiving initial chemotherapy, ramucirumab (Cyramza® ) could be an option Immunotherapy • Designed to boost the body’s natural defenses to fight the cancer o Pembrolizumab (Keytruda® ), an anti-PD-1 checkpoint immunotherapy approved for patients with advanced, relapsed stomach cancer that expresses programmed death ligand 1 (PD-L1) Palliative Care • Lengthens life and relieves symptoms for those with metastatic gastric cancer American Society of Clinical Oncology (2019). Stomach cancer: treatment options. Available at: https://www.cancer.net/cancer- types/stomach-cancer/treatment-options Cancer Research Institute (2019). How is immunotherapy changing the outlook for patients with stomach cancer? Available at: https://www.cancerresearch.org/immunotherapy/cancer-types/stomach-cancer
  7. 7. 089GC Reference Guide | Page 7 of 12 www.i3Health.com V. SYSTEMIC THERAPY FOR GASTRIC CANCER: ADVERSE EVENTS Potential Adverse Events 5-Fluorouracil and Capecitabine • Palmar-plantar syndrome: o Soreness of the palms of the hands and soles of the feet o Tingling, numbness, pain, and dryness o Rarely, palmar-plantar syndrome can cause a spasm in the arteries that supply the heart with blood, causing chest pain similar to that of angina Cisplatin • Hearing loss • Kidney damage o To avoid this, drink plenty of water during treatment Epirubicin • Red or pink urine for a few days after treatment • Skin that is more sensitive to sunlight; reddening in areas where the patient has had radiotherapy in the past • Damage to the heart muscle (rare) Oxaliplatin • Neuropathy (temporary or permanent damage to the nerves that affect the fingers and toes, causing numbness or pins and needles) Irinotecan • Increased sweating and salivary production • Watery eyes • Abdominal cramps and sometimes severe diarrhea Docetaxel • Fluid retention • Temporary nail discoloration • Itchy skin rash • Palmar-plantar syndrome (see description under “5-Fluorouracil and Capecitabine” above) • Simple numbness or tingling in the hands and feet • About 1 in 4 patients suffer from an allergic reaction during the first or second infusion Trastuzumab • Common: allergic reactions that can involve chills, fever, itchy rash, feeling of sickness, breathlessness, wheezing, headaches, flushes, and/or faintness • Heart problems that usually resolve once treatment is discontinued Trifluridine/ Tipiracil • Myelosuppression: o Anemia o Neutropenia o Thrombocytopenia o Febrile neutropenia European Society for Medical Oncology (2012). Stomach cancer: a guide for patients. Available at: https://www.esmo.org/content/download/6635/115239/file/EN-Stomach-Cancer-Guide-for-Patients.pdf Lonsurf® (trifluridine/tipiracil) prescribing information (2019). Taiho Oncology. Available at: https://www.taihooncology.com/us/prescribing-information.pdf
  8. 8. 089GC Reference Guide | Page 8 of 12 www.i3Health.com Potential Adverse Events (cont.) Pembrolizumab • Pneumonitis (a lung condition): shortness of breath, chest pain, or new/worse cough • Colitis (intestinal problems that can lead to intestinal tears or perforations). Signs/symptoms: o Diarrhea or more bowel movements than usual o Stools that are black, tarry, sticky, or have blood or mucus o Severe abdomen pain/tenderness • Hepatitis (inflammation of the liver). Signs/symptoms: o Yellowing of the skin or the whites of the eyes o Nausea or vomiting o Pain on the right side of the abdomen o Dark urine o Loss of appetite o Easy bleeding or bruising • Hormone gland problems, especially the thyroid, pituitary, adrenal glands, and pancreas. Signs/symptoms: o Rapid heartbeat o Weight loss or gain o Increased sweating o Increased hunger or thirst o Increased frequency of urination o Hair loss o Chills o Constipation o Deepening of the voice o Muscle aches o Dizziness or fainting o Unusual headaches or headaches that will not go away • May cause nephritis and kidney failure. Signs include change in the amount or color of urine • Skin problems o Rash, itching, blisters, peeling o Skin sores o Painful sores or ulcers in the mouth, nose, throat, or genital area • Problems in other organs: o Vision changes o Severe or persistent muscle or joint pains; severe muscle weakness o Anemia (low red blood cell count) o Sarcoidosis § Swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, and/or eye pain o Encephalitis § Confusion, fever, muscle weakness, balance problems, nausea or vomiting, stiff neck, memory problems, and/or seizures o Myocarditis § Shortness of breath, irregular heartbeat, feeling tired, and/or chest pain Keytruda® (pembrolizumab) prescribing information (2018). Available at: http://keytruda.com
  9. 9. 089GC Reference Guide | Page 9 of 12 www.i3Health.com Potential Adverse Events (cont.) Ramucirumab • Hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal hemorrhagic events • Arterial thromboembolic events, including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia • Hypertension o Important to control blood pressure before treatment and monitor throughout treatment • Infusion-related reactions. Signs/symptoms: o Rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia o In severe cases: bronchospasm, supraventricular tachycardia, and hypotension • Gastrointestinal perforations • Impaired wound healing o Withhold treatment prior to surgery • Proteinuria, including nephrotic syndrome o Important to monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio o Withhold ramucirumab for urine protein levels ³2 g over 24 hours o Reinitiate ramucirumab at a reduced dose once urine protein level returns to <2 g over 24 hours o Permanently discontinue ramucirumab for urine protein levels >3 g over 24 hours or in the setting of nephrotic syndrome • Thyroid dysfunction • Embryofetal toxicity • In patients with Child-Pugh B or C cirrhosis, may cause clinical deterioration manifested by new-onset or worsening encephalopathy, ascites, or hepatorenal syndrome Cyramza® (ramucirumab) prescribing information (2018). Available at: http://cyramza.com
  10. 10. 089GC Reference Guide | Page 10 of 12 www.i3Health.com VI. GASTRECTOMY: PATIENT GUIDELINES FOR ADVERSE EVENTS Gastrectomy: Adverse Events Surgical Complications • Wound infection • Leaking from a join made during surgery • Stricture (stomach acid leaks into the esophagus and causes scarring, leading to the esophagus becoming narrow and constricted) • Chest infection • Internal bleeding • Blockage of the small intestine Vitamin Deficiency • One of the stomach’s functions is to absorb vitamins, particularly B12, C, and D, from food. If the stomach is removed, the patient may not get these vitamins • Lack of these vitamins causes o Anemia o Increased vulnerability to infection o Osteoporosis and weakened muscles • Patient may need to make dietary changes or take vitamin supplements Weight Loss • Patient may feel full quickly and eat less • Important to consult a dietician Dumping Syndrome • Food moves too fast into the small intestine, particularly sugary and starchy food o Before the gastrectomy, the stomach digested most of the sugar and starch. Now, the small intestine has to draw in water to digest sugar and starch • 1.5 liters of water can enter the small intestine, much of it taken from blood. This can cause a sudden fall in blood pressure, resulting in the following symptoms: o Faintness o Sweating o Palpitations o A need to lie down • Extra water in the small intestine can cause the following symptoms: o Bloating o Rumbling noises o Nausea o Indigestion o Diarrhea • To ease the symptoms of dumping syndrome: o Rest for 20-45 minutes after each meal o Eat slowly o Avoid sugary foods o Slowly increase dietary fiber intake o Avoid soup and other liquids o Eat smaller, more frequent meals
  11. 11. 089GC Reference Guide | Page 11 of 12 www.i3Health.com Gastrectomy: Adverse Events (cont.) Morning Vomiting • Bile (fluid used by the digestive system to break down fats) and digestive juices build up in the duodenum (the first part of the small intestine) overnight • Because the stomach is smaller, an uncomfortable feeling of fullness may occur, triggering the vomit reflex • Indigestion medication may help to reduce these symptoms • Consult with a general practitioner Diarrhea • The vagus nerve, which helps to control the movement of food through the digestive system, is sometimes cut during a gastrectomy. This causes diarrhea Heartburn (Acid Reflux) • To relieve heartburn, sit in an upright position for at least one hour after eating • Medications can also provide symptom relief National Health Service (2018). Gastrectomy complications. Available at: https://www.nhs.uk/conditions/gastrectomy/risks/
  12. 12. 089GC Reference Guide | Page 12 of 12 www.i3Health.com VII. POST-GASTRECTOMY EATING GUIDELINES Patient Instructions on Post-Gastrectomy Eating • Eat 6 or more small meals a day instead of 3 main meals o This will help you to eat the right amount of food, even though your stomach is smaller or gone • Eat slowly and chew your food well to help with digestion o This will enable you to stop eating before you get too full and feel uncomfortable • Do not drink more than 4 ounces (1/2 cup) of liquid during meals o This will allow you to eat enough solid food without getting too full and will slow down digestion of your food • Drink most of your liquids at least 1 hour before or 1 hour after meals to prevent dehydration • Drink about 8-10 glasses of liquid per day (a glass is considered 8 ounces) o Avoid carbonated beverages if they make you feel full • Test your tolerance to sweets o Sugar in foods and liquids may cause water to be drawn into your stomach or small intestine. Your food will then move too quickly through your small intestine. This is called dumping syndrome. It may cause cramping, stomach pain, or diarrhea. These symptoms start within about 20 minutes of eating o Low blood sugar can happen to 1-2 hours after a sugary meal. Symptoms include feeling weak, hungry, nauseous, anxious, shaky, and sweaty. The symptoms can be controlled by changing your diet and watching what you eat. Ask a dietitian for more information • Test your tolerance to fats o You may have trouble digesting large amount of fat. Try a small amount first and then increase it slowly o Foods high in fat: § Butter, margarine, and oils § Mayonnaise and gravies § Creamy salad dressings and cream cheese § Potato and corn chips § Rich desserts and fried foods • Slowly bring dairy products back into your diet o Some people may become lactose intolerant after having a gastrectomy. This means that they have trouble digesting lactose, a type of alcohol sugar found in dairy products o Sometimes, lactose intolerance that develops after surgery will go away with time o Symptoms of lactose intolerance (gas, bloating, and diarrhea) usually start soon after eating dairy products o To test your tolerance to dairy foods, start by drinking a 4-ounce (1/2 cup) serving of milk. If you do not have any symptoms of lactose intolerance, you can start eating more dairy foods o Examples of foods with large amounts of lactose are milk, ice cream, and soft cheeses o If you become lactose intolerant, you may still be able to eat hard cheeses, yogurt, and butter. These foods have smaller amounts of lactose than other dairy products o If you think you may be lactose intolerant, consult your dietitian o Products such as lactose-free milk, tablets, or drops can help you to digest dairy products o You may want to try dairy products again in a couple of months to see if you can tolerate them • You may need a monthly shot of vitamin B12 and vitamin and mineral supplements • Tell your doctor if you are losing weight Memorial Sloan Kettering Cancer Center (2014). Eating after your gastrectomy or esophagogastrectomy. Available at: https://www.mskcc.org/cancer-care/patient-education/eating-after-your-gastrectomy-esophagogastrectomy

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