15. Carcinoma Pancreas powerpoint presentation.pptx

Presentation on Carcinoma Pancreas

1. CARCINOMA PANCREAS PRESENTER: D r . ABHISHEK MEWARA MODERATOR: D r . MANISH CHATURVEDI DATE: 5.10.2024 1

2. OVERVIEW INTRODUCTION ANATOMY SIGNS AND SYMPTOMS DIAGNOSTIC WORKUP STAGING TREATMENT SURGERY CHEMOTHERAPY RADIOTHERAPY 2

3. INTRODUCTION 3

4. 4 th leading cause of cancer death. Males > Females (1.3:1) Risk factors — Smoking, chronic pancreatitis, diabetes mellitus, H. pylori, positive family history. Pathologically : Adenocarcinoma is the MC. Spread by local extension, regional lymphatics and distant metastasis (mostly to liver, peritoneum, lung), 80% are metastatic at the time of presentation. Median survival: 8 - 14 months. Associated with BRCA 1, BRCA 2, and PALB 2 mutations, familial atypical multiple mole melanoma syndrome, Peutz-Jegher syndrome, FAP, HNPCC, hereditary pancreatitis, ataxia telangiectasia, and Li-Fraumeni syndrome. 4

5. ANATOMY 5

6. The pancreas lies in the retroperitoneal space of the upper abdomen at the level of the first two lumbar vertebrae. It is divided into head (including uncinate process), neck, body, tail. It has intimate contact with stomach, duodenum, jejunum, kidneys, spleen, and major vessels, all of which can be involved by direct tumor extension. Tumors in the pancreatic head often invade or compress the common bile duct, causing jaundice and dilatation of the bile and pancreatic ducts and gallbladder . The rich lymphatic drainage of the pancreas is interconnected with duodenal lymphatics. Regional drainage of the pancreatic head is to the peripancreatic, pancreaticoduodenal, porta hepatis, celiac, and superior mesenteric lymph nodes. 6

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8. SIGNS AND SYMPTOMS 8

9. SIGNS Icterus Supraclavicular lymph node (Virchow’s node) Palpable abdominal mass Hepatosplenomegaly Ascites Palpable gall bladder (Courvoisier's sign) Palpable rectal shelf ( Blumer’s shelf) Superficial migratory thrombophlebitis (Trousseau’s syndrome) 9

10. SYMPTOMS 10 Head, neck and uncinate process of pancreas Body and tail of pancreas Obstructive jaundice Vague pain abdomen and upper back Pruritus Jaundice — late manifestation High coloured urine Tail tumours - Left sided portal hypertension , Upper Gl bleed , Splenomegaly Black tarry stool Steatorrhea

11. DIAGNOSTIC WORKUP 11

12. Accurate diagnostic imaging is used to determine whether a patient with pancreatic cancer is a candidate for surgical resection or has an incurable disease. CT is the most commonly used study and is very effective when performed according to a standard pancreatic protocol with thin slices and triphasic cross-sectional imaging. CT scans can demonstrate masses in the pancreas or dilatation of the pancreatic duct or the common bile duct. Sensitivity and specificity of CT are about 90% each. Endoscopic USG may be useful for staging (e.g. nodal status), determination of major vessel invasion, and for FNA for the pathologic determination of tumor. To determine vascular invasion, there are three options: Helical CT, MR arteriography, and Endoscopic USG. 12

13. Percutaneous FNA of suspicious abnormalities identified on CT scan can confirm the diagnosis of pancreatic cancer with 80 to 90% sensitivity and 100% specificity. A common histologic hallmark of pancreatic adenocarcinoma is an associated desmoplastic reaction that can vastly overestimate the malignant cell mass. Investigation of choice for staging in these patients is PET-CT. 13

14. CA 19-9 An important predictive and prognostic marker. Normal value is less than 37 U/ml. Used in cases where diagnosis is doubtful. Elevated in 75% of patients. But also elevated in benign conditions of the pancreas, liver, and bile ducts. Used to measure response to therapy or for screening for recurrence. 14

15. STAGING 15

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17. TREATMENT 17

18. 1. SURGERY 18

19. Indications: T1, T2, and rarely T3. 85% are not resectable at presentation. Procedure: WHIPPLE’S SURGERY (PANCREATICO-DUODENECTOMY) Includes en -bloc resection of the duodenum, head of the pancreas, immediate peripancreatic nodal tissue, the pylorus, and the antrum of the stomach. At least 15 draining lymph nodes must be dissected. In an effort to minimize surgical morbidity, pylorus-preserving pancreaticoduodenectomy and laparoscopic resection techniques have been developed. Pylorus sparing pancreatico -duodenectomy potentially improves gastrointestinal function without compromising the oncologic management. 19

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21. CRITERIA FOR UNRESECTABILITY Extra-pancreatic involvement. Encasement or occlusion of the superior mesenteric vein or the SMV-portal vein confluence. Direct involvement of the superior mesenteric artery, inferior vena cava, aorta, or celiac axis. 21

22. MODIFIED WHIPPLE/LONGMIRE AND TRAVERSO PROCEDURE It is done in all cases except: If duodenum is involved. If negative margins cannot be attained. Structures cut: Pylorus CBD, and a cholecystectomy is done. Head and neck with part of body of the pancreas. Duodenum. 22

23. After resection the parts left are: Cut end of CBD Cut end of gallbladder Cut end of pancreas Jejunum After this jejunum anastomosed with the pancreas, stomach and CBD. These procedure are: Hepatico / choledochojejunostomy Gastrojejunostomy Pancreaticojejunostomy 23

24. 2. CHEMOTHERAPY 24

25. Indications: Adjuvant treatment after surgery (with EBRT) Adjuvant treatment with EBRT (unresectable disease) Palliative therapy Gemcitabine is used mainly. 25

26. PREFERRED AGENTS: GEMCITABINE COMBINATIONS Inj. Gemcitabine- Standard Dose: 1000 mg/m 2 over 30 minutes, weekly for 3 weeks every 28 days. Fixed dose rate gemcitabine (10 mg/m 2 /min) may substitute for standard infusion of gemcitabine over 30 minutes. Combinations are- Gem-Ox Gem-Capecitabine Gem-Erlotinib Gem-Nab-paclitaxel 26

27. Currently, alternative adjuvant chemotherapy regimens (with or without radiotherapy) includes- Gemcitabine alone 1000 mg/m 2 on days 1, 8, and 15 with a 1-week break. 5-FU 225 mg/m 2 by continuous IV infusion throughout radiation therapy followed by four to six courses of bolus 5-FU weekly, or gemcitabine 1000 mg/m 2 on days 1, 8, and 15 with a 1-week break. 5-FU 425 mg/m 2 by IV push 1 hour after leucovorin 20 mg/m 2 by IV push daily for 4 days during the first week of radiation therapy and for 3 days during the fifth week of radiation therapy followed by four to six courses of bolus 5-FU weekly or gemcitabine 1000 mg/m 2 on days 1, 8, and 15 with a 1-week break. 27

28. Capecitabine 1,500 mg/m 2 daily in divided doses with radiation therapy followed by four to six courses of bolus 5-FU weekly or gemcitabine 1000 mg/m 2 on days 1, 8, and 15 with a 1-week break. 28

29. METASTATIC PANCREATIC CANCER OS without palliative chemo: 3-6 months. OS with palliative chemo: 6-9 months. OS benefits only in good prognosis patients. Stenting is done for jaundice. Good pain management must be provided. Adequate nutrition must be given. 29

30. CHEMOTHERAPY FOR METASTATIC DISEASE Current recommendations- FOLFIRINOX 5 FU 400 mg/m 2 IV on day 1 followed by 2400 mg/m 2 continuous IV infusion over 46 hours, leucovorin 400 mg/m 2 IV on day 1, irinotecan 180 mg/m 2 IV on day 1, and oxaliplatin 85 mg/m 2 IV on day 1 given every 14 days. Gemcitabine plus nab-paclitaxel Gemcitabine 1000 mg/m 2 IV and nab-paclitaxel 125 mg/m 2 IV weekly for 3 weeks with 1 week break. Gemcitabine plus erlotinib Erlotinib 100 to 150 mg PO daily plus gemcitabine 1000 mg/m 2 IV weekly for 3 weeks with a 1 week break. Capecitabine and gemcitabine Gemcitabine 1000 mg/m 2 IV weekly for 3 weeks with 1 week break and capecitabine 1500 mg/m 2 PO daily in twice-daily divided doses on days 1 to 14 every 21 days. 30

31. Capecitabine and oxaliplatin Gemcitabine 1000 mg/m 2 IV weekly for 3 weeks with 1 week off plus oxaliplatin 130 mg/m 2 on day 1 every 3 weeks. Single-agent therapy with gemcitabine Gemcitabine 1000 mg/m 2 IV weekly for 3 weeks with 1 week off. 31

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33. CAPECITABINE Another name- Xeloda. MOA- An orally administered prodrug that is converted to fluorouracil intracellularly. When this is converted to the active nucleotide, it inhibits the enzyme thymidylate synthetase and blocks DNA synthesis. The triphosphate may also be mistakenly incorporated into RNA, which interferes with RNA processing and protein synthesis. Primary indications- 1. Metastatic breast cancer that is resistant to anthracyclines and paclitaxel containing chemotherapy regimens. May also be used in patients in whom anthracyclines are contraindicated. 2. Colorectal, small bowel, stomach, pancreas, and biliary carcinomas. 33

34. Usual dosage and schedule- Generally taken with water, twice daily (about 12 hours between doses) within 30 minutes after a meal. 1. 1000 to 1250 mg/m 2 orally twice daily for 2 weeks as a single agent, followed by a 1- week rest, given as 3-week cycles. 2. 850 to 1250 mg/m 2 orally twice daily for 2 weeks when used in combination with other drugs, followed by a 1-week rest, given as 3-week cycles. 3. 800 mg/m 2 orally twice daily 5 days per week during radiotherapy, as a radiosensitizer. 34

35. Special precautions- Increase in PT-INR may be seen in patients previously stable on oral anticoagulants. Patients with moderate renal impairment (Creatine Clearence 30 to 50 mL/minutes) require a 25% dosage reduction. Diarrhea may be severe and require fluid and electrolyte replacement. Phenytoin levels should be monitored, as elevated levels may occur. 35

36. Toxicities- 1. Myelosuppression and other hematologic effects. 2. Nausea, vomiting, and other GI effects. 3. Mucocutaneous effects- Hand and foot syndrome is common and may be severe. Dermatitis is also common, as is stomatitis, but it is uncommon that these are severe. Eye irritation and increased lacrimation are occasional. 4. Miscellaneous effects- a. Fatigue b. Paresthesia c. Hyperbilirubinemia d. Fever e. Headache or dizziness f. Cardiotoxicity 36

37. TARGETED THERAPIES Growth factors are expressed at higher levels in pancreatic cancer. Erlotinib: Small molecule tyrosine kinase inhibitor of the EGFR. Cetuximab: EGFR monoclonal antibody. Bevacizumab: anti VEGF monoclonal antibody. Sorafenib: Inhibitor of Raf 1 and VEGF 2. 37

38. ERLOTINIB Another name- Tarceva . MOA- Inhibits intracellular phosphorylation of the tyrosine kinase associated with epidermal growth factor receptor (EGFR). Usual dosage and schedule. Give at least 1 hour before or 2 hours after food. 150 mg PO daily for lung cancer. 100 mg PO daily for pancreatic cancer. Primary indications- NSCLC Pancreatic cancer (with gemcitabine). 38

39. Special precaution- May be associated with ILD like events, manifested by unexplained dyspnea, cough, and fever. If this occurs, erlotinib therapy should be discontinued and management of the pulmonary condition is instituted. GI perforation; bullous, blistering, and exfoliative skin conditions, suggestive of TEN; and ocular disorders, including corneal perforation or ulceration, have been reported. Toxicities- Myelosuppression and other hematologic effects. Nausea, vomiting, and other GI effects. 39

40. 3. Mucocutaneous effects. Rash is common and the most common reason for dose interruption; stomatitis and Keratoconjunctivitis are occasional. 4. Miscellaneous effects- Systemic- Fatigue, weight loss, edema, fever. Hepatic. Transaminase elevations, and occasionally associated with increased bilirubin, but are rarely life-threatening. Bone pain and myalgia Dyspnea, cough Anxiety, depression, headache, and neuropathy Myocardial ischemia or infarction Cerebrovascular accidents 40

41. CETUXIMAB Other names- EGFR antibody, C225, Erbitux. MOA- EGFR antibody that blocks the ligand-binding site and inhibits proliferation of cells. Primary indications- 1. Carcinoma of head and neck, in combination with radiation therapy or as first-line therapy with platin-based therapy plus fluorouracil for recurrent locoregional advanced or metastatic disease, or after failure of platinum-based therapy. 2. Colon cancer when KRAS is wild-type either as- a. First-line therapy in combination with FOLFIRI, or b. After failure of irinotecan and oxaliplatin-based regimens. 3. Lung cancer if EGFR amplification is present. 41

42. Usual dosage and schedule- 400 mg/m 2 IV loading dose administered over 2 hours on day 1. Then 250 mg/m 2 IV maintenance doses administered over 1 hour weekly thereafter. May be administered in combination with other agents. Special precautions- Serious infusion reactions, some fatal, may occur. One hour observation period is recommended following a cetuximab infusion. Cardiopulmonary arrest or sudden death has occurred in some patients receiving cetuximab in combination with radiation therapy. Severe hypomagnesemia is seen in 10% to 15% of patients, and all patients should have magnesium levels monitored throughout the persistence of cetuximab (8 weeks). 42

43. Toxicities- 1. Myelosuppression and other hematologic effects. 2. Nausea, vomiting, and other GI effects. 3. Mucocutaneous effects. Acne-like rash is common. Stomatitis is occasional when used alone, but universal when used in combination with radiation therapy. Severe radiation dermatitis may be seen when used concurrently with radiation therapy. 4. Miscellaneous effects- a. Asthenia, headache and back pain. b. Weight loss, peripheral edema, and dehydration. c. Infusion reactions with allergic or hypersensitivity reactions, fever, chills, or dyspnea. e. Electrolyte depletion, particularly hypomagnesemia. 43

44. SORAFENIB Another name- Nexavar . MOA- Inhibition of multiple tyrosine kinases and serine/threonine kinases within tumor cells and tumor vasculature resulting in decreased tumor cell proliferation and reduction of tumor angiogenesis. Primary indications- 1. Renal cell carcinoma. 2. Hepatocellular carcinoma. 3. Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. 4. GI stromal tumors with prior imatinib or sunitinib treatment. Usual dosage and schedule- 400 mg PO twice daily either without food or with a moderate fat meal. 44

45. Toxicities- 1. Myelosuppression and other hematologic effects. 2. Nausea, vomiting, and other GI effects. 3. Mucocutaneous effects- Alopecia, pruritis . 4. Miscellaneous effects- Hypertension Fatigue Sensory neuropathy Hypophosphatemia Cardiac ischemia or infarction 45

46. BEVACIZUMAB Another name- Avastin. MOA- Binds VGEF and prevents interaction of VEGF with its receptors on the surface of endothelial cells. This in turn impairs endothelial cell proliferation and new blood vessel formation, impeding tumor growth and metastasis. Primary indications- 1. Breast, colon, kidney, rectum, and non-squamous NSCLC, usually with other agents. 2. Glioblastoma, alone or with other agents. 3. Ovarian, fallopian tube, or primary peritoneal cancer in the recurrent, platinum resistant setting. 4. Cervical cancer in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent or metastatic disease. 46

47. Usual dosage and schedule- 1. 5 to 10 mg/kg IV once every 2 weeks. 2. 15 mg/kg IV once every 3 weeks. Special precautions- GI perforation occurs in up to 4% of patients, and may have a fatal outcome. Impaired wound healing may rarely lead to anastomotic dehiscence. Bevacizumab should not be initiated for at least 28 days following major surgery. 47

48. Toxicities- 1. Myelosuppression and other hematologic effects. 2. Nausea, vomiting, and other GI effects. 3. Mucocutaneous effects. Dry skin, skin discoloration, stomatitis, and exfoliative dermatitis are occasional to common. Alopecia, skin ulcers, and nail changes are uncommon. 4. Immunologic effects and infusion reactions. Infusion reactions with hypertension, wheezing, stridor, desaturation, chest pain, headaches, and diaphoresis are uncommon. 5. Miscellaneous effects- a. Fatigue, weakness, and headache. b. Cardiovascular and respiratory—Hypertension is common and occasionally is c. Neurologic—Dizziness is common d. Metabolic—Proteinuria is common e. Osteonecrosis of the jaw. 48

49. PACLITAXEL, PROTEIN-BOUND Other names- Nanometer albumin-bound paclitaxel (nab-paclitaxel), Abraxane. MOA- Albumin binding circumvents the requirement for Cremophor vehicle for paclitaxel and its associated toxicity, and exploits albumin receptor–mediated endothelial transport. As with parent compound, intratumor paclitaxel results in enhanced formation and stabilization of microtubules. Mitotic arrest is seen and is associated with accumulated polymerized microtubules. 49

50. Primary indications- 1. Metastatic carcinoma of the breast 2. In combination with carboplatin for the initial treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who are not candidates for curative surgery or radiation therapy. 3. In combination with gemcitabine for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas. Usual dosage and schedule- 260 mg/m 2 IV over 30 minutes every 3 weeks. Special precautions- Hypersensitivity reactions may occur during the infusion of nab-paclitaxel. Premedication, as is used with paclitaxel, is not required. 50

51. Toxicities- 1. Myelosuppression and other hematologic effects. 2. Nausea, vomiting, and other GI effects. 3. Mucocutaneous effects- Alopecia is universal; mucositis is occasional. 4. Hypersensitivity reactions. 5. Miscellaneous effects- Cardiovascular events. b. Sensory neuropathy is common and may be progressively worse with time. Recovery may take months to years. c. Asthenia. d. Ocular or visual disturbances. f. Abnormal liver function tests. g. Myalgias and arthralgias. 51

52. 3. RADIOTHERAPY 52

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55. TREATMENT PLANNING Position: Supine with arms above the head. Immobilization: Thermoplastic cast/ Aquaplast / Wing board. CECT done: Till top of diaphragm till L4. OAR: Small bowel, liver, stomach, kidneys, spinal cord. CT-based treatment planning allows the construction of normal tissue dose–volume histograms and the generation of treatment plans that optimize radiation dose delivery to tumor while sparing critical normal tissues. Multiple field, fractionated, external beam techniques utilizing high-energy photons to deliver 45 to 50 Gy in 1.8 Gy fractions to tumor bed, unresected or residual tumor, and lymph node–bearing areas at risk. After the primary fields, a boost field can be designed to include unresected or gross residual disease, as defined by CT scans and clips, while excluding most of the stomach and small bowel. 55

56. RTOG CONTOURING GUIDELINES FOR ADJUVANT RT CTV includes: Post-operative bed: Based on location of initial tumor from pre-operative imaging and pathology reports Anastomoses: Pancreaticojejunostomy Choledochal or hepaticojunostomy Abdomianl nodal regions: Peripancreatic Celiac Superior mesenteric Porta hepatis Para-aortic 56

57. SBRT Stereotactic Body Radiation Therapy. Higer dose per fraction in fewer number of fractions. Total dose: 25-30 Gy in 4-5 fractions. Higer dose to region of vessel encasement. Advantages: Short duration Efficacy Favorable toxicity 57

58. REFERENCES GRAY’S ANATOMY 41 ST EDITION GLOBOCAN PEREZ DEVITA NCCN V. 2024 AJCC 8 TH EDITION GOOGLE SEARCH ENGINE 58

59. THANK YOU, AND HAVE A NICE DAY! 59

60. FIELD BORDERS AP/PA FIELDS Head of Pancreas lesions- Superior border: Upper border of T11. Inferior border: Lower border of L3. Right border: Extended to cover the duodenum and porta hepatis. Left border: 2cm to the left from left edge of vertebral body. 60

61. Body of Pancreas lesion- Superior border: Above T11. Inferior border: Lower border of L3. Right border: 2cm to the right from the right vertebral body edge. Left border: Extend to include the splenic hilum. 61

62. FIELD BORDERS LATERAL FIELDS Anterior: 1.5 – 2 cm anterior to the tumor. Posterior: 1.5 cm behind the anterior portion of the vertebral body. Superior: Upper border of T11. Inferior: Lower border of L3. 62