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4/27/2015
Internal Medicine
Board Review Course 2015
Oncology I
Devapiran Jaishankar
Associate Professor
Quillen College of Medicine
East Tennessee State University
Disclosure statement
• I have no disclosures relevant to this presentation
ABIM
Test taking strategies
• The ABIM is logical and rational
• The ABIM is usually non invasive
• The ABIM is generally cost effective
• Look for a single unifying hypothesis/ theory
• Ask yourself what is the principle being tested on that question
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ABIM
Test taking strategies II
• The longer the question……. Read the answers/ choices first
• Look for the “distractors” and weed them out of the question quickly
• There are no “evers” or “nevers” in medicine
• The ABIM is analytical not emotional
• Questions are data and evidence based (no scientific or political debates)
• If.. its hard to get the answer correct its even harder to set the question
Topics covered
• Lung cancer
– Non small cell lung cancer
– Small cell lung cancer
• GI cancers
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–
–
–
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• Oncologic emergencies
• Cancer treatment toxicity
• Cancer screening
Esophageal
Gastric
Hepatocellular
Pancreatic
Colon
• Breast cancer
• Carcinoma of Unknown
Primary
Question #1
• A 56 year old male is evaluated 4 weeks after a pulmonary lobectomy for a
spiculated lesion in the RUL of the lung. Pathology reveals poorly
differentiated adenocarcinoma of the lung (TTF-1 +) with clear margins, no
pleural or lympho vascular invasion and with 7 lymph nodes negative for
metastatic carcinoma. A pre op MRI Brain was negative and a PET-CT
revealed a 2.7 cm RUL pulmonary lesion with a SUV of 8.5 but no distant
disease. Which of the following is the appropriate next step in the
management.
•
•
•
•
A:
B:
C:
D:
Radiation treatment
Platinum based doublet chemotherapy
Concurrent chemotherapy and radiation
Surveillance with periodic physical exams and imaging
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Analysis of question #1
Answer: D
• Oncology question: Lung cancer
• Middle aged male with resected lung cancer
• Small lesion; T1 size; clear margins; nodes negative
• MRI Brain neg and PET-CT no distant disease = No mets
•
•
•
•
Thus, the question being asked is…. post resection, what next?
Adjuvant treatment ??
XRT vs chemo vs chemo+XRT vs surveillance
Depends on stage
• PRINCIPLE TESTED:
Stage IA NSCLC does not require any adjuvant treatment
Incidence & Prognosis by Stage
Incidence by TNM staging
5 year overall survival
• Stage I
25%
• Stage I
60-75%
• Stage II
7%
• Stage II
35-60%
• Stage III
32%
• Stage III
24%
• Stage IV
36%
• Stage IV
3.6%
Non Small Cell Lung Cancer
Treatment-Schema
STAGE IA
STAGE II
STAGE IIIA
STAGE IIIB
STAGE IV
SURGERY ONLY
Surgery + ADJUVANT CHEMOTHERAPY
Concurrent chemo-RT +/- surgery
CONCURRENT CHEMO-RT (Curative intent)
NON CURATIVE CHEMO ONLY
Adjuvant chemotherapy with Platinum doublet
Concurrent Chemo-RT uses Platinum doublet
Metastatic NSCLC: Platinum doublet + Targeted therapy
Histology now defines the doublet
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Question #2
• A reasonably fit 69 year old lady with a 6o pack year h/o smoking presents
with progressive dyspnea, cough and weight loss. A CXR reveals a large
left pleural effusion with a 3.0 cm left lingular mass. A trans bronchial
biopsy of the mass is positive for squamous cell carcinoma. Pleural fluid
analysis is exudative, but cytology-negative for malignant cells and a
subsequent therapeutic thoracentesis and pleural fluid analysis is
unchanged. A PET-CT and MRI Brain show no distant metastatic disease.
Which of the following is the most appropriate modality of treatment.
•
•
•
•
A:
B:
C:
D:
Chest tube drainage followed by resection of the lung mass
Concurrent chemotherapy and radiation
Systemic multi agent chemotherapy
Targeted therapy with Erlotinib or Crizotinib
Explanation for question #2
Answer: C
• PRINCIPLE TESTED:
Pleural effusion in NSCLC defines stage IV disease
• Liver, Brain, Bone and Adrenals are frequent metastatic sites
• Primary treatment is with systemic chemotherapy (platinum doublet)
• No role for surgery or XRT (except for palliation)
• Median survival is 4-6 months without treatment
• Median survival is 12-14 months with treatment (with better quality of life)
• 15% of non squamous Lung cancers have EGFR mutations or ALK
rearrangement amenable to targeted therapy with Erlotinib or Crizotinib
Question #3
•
Which of the following complications is not typically seen in small cell
lung cancer (SCLC)
• A:
Cerebellar degeneration
• B:
Hyponatremia
• C:
Hypercalcemia
• D:
Myasthenia Gravis
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Explanation for question #3
Answer: C
• PRINCIPLE TESTED:
Para neoplastic syndromes in Lung cancer
• Small cell lung cancer vs Non small cell lung cancer
• Subtypes of Non small cell lung cancer and characteristics
Lung Cancer
Subtypes and Features
SQUAMOUS
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–
–
–
–
–
–
–
–
Central
95% smokers
60% mets
Hypercalcemia
ADENO
LARGE-C
SMALL-C
Periph
50%
80%
Periph
90%
80%
Central
almost 100%
almost 100%
Hypercoag
HPOA
Nonsmokers
Women
Older
Eaton-L
SIADH
Ectopic ACTH
Neuropathy
Cerebellar
degeneration
Question #4
• Choose the incorrect answer amongst the following surgical interventions
in lung cancer
• A:
NSCLC with chest wall involvement
• B:
NSCLC with a single brain metastasis
• C:
NSCLC with supraclavicular adenopathy
• D:
SCLC with 1.5 cm RML lesion
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Explanation for question #4
Answer: C
• Principles of resection in lung cancer are being tested
•
•
•
•
•
Can resect
chest wall and rib despite involvement albeit challenging
early stage small cell carcinoma
oligometastatic disease, particularly the single brain or adrenal metastasis in a
fit stage IV-NSCLC patient but without curative intent
ipsilateral satellite nodule (same or different lobe)
•
Cannot resect N3 nodes:
•
Cannot resect mediastinal invasion:
•
Cannot resect contralateral satellite nodules
– Contralateral hilar or mediastinal nodes
– Ipsilateral supraclavicular nodes
– Vertebra, Esophagus, trachea, heart and great vessel involvement
Question #5
• A 44 year old fit female karate instructor, non smoker, is diagnosed with
stage IV adenocarcinoma of the lung with extensive liver mets. She is keen
on aggressive chemotherapy treatment but is started on oral Erlotinib after
her pathology report reveals an EGFR mutation from the original biopsy.
Which of the following is not an expected side effect of Erlotinib
• A:
Fatigue and asthenia
• B:
Acneiform rash on the face, trunk and extremities.
• C:
Diarrhea
• D:
Systolic dysfunction and cardiomyopathy
Explanation for question #5
Answer: D
• PRINCIPLE TESTED:
• Oncology toxicity question, EGFR testing in stage IV NSCLC
• Toxicity of Erlotinib: Tyrosine Kinase Inhibitor (TKI)
• The rash with Erlotinib may be first noted by the Internist and will be
followed by the internist all through the course of treatment for many
months
• In general the toxicity is mild and very well tolerated and hence the
attraction of oral targeted therapy
• Recently some TKI’s such as Imatinib and Sunitinib reported with cardiac
side effects such as fluid retention/ cardiomyopathy, but not Erlotinib
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Question #6
• A 62 year old heavy smoker is diagnosed with limited stage SCLC with an
endobronchial lesion in the RUL of the lung and is treated with concurrent
chemotherapy (Cisplatin-Etoposide) and twice daily radiation as per the
Turissi protocol. After 4 cycles of chemotherapy the patient has achieved a
complete response. What is the next course of action
• A: Resect the lesion to secure the complete response with negative margins
• B: Two additional cycles of chemotherapy as consolidation treatment
• C: Send the patient for PCI (Prophylactic cranial irradiation) evaluation
• D: No further treatment, surveillance with periodic imaging
Explanation for question #6
Answer: C
• PRINCIPLE TESTED:
Treatment of small cell lung cancer:
Role of PCI:
Small Cell Lung Cancer
Limited stage treatment:
(30% cure rate)
Extensive stage treatment:
( 5% survival at 5 years)
Concurrent XRT + Chemo x 4 cycles
Chemotherapy only x 6 cycles
Chemotherapy: Cisplatin + Etoposide
PROPHYLACTIC CRANIAL IRRADIATION: PCI
an option for good responders
significant survival benefit (15-20%) possibly at the cost of late cognitive
decline (onset > 2yrs)
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Section I Review
Lung Cancer
• Management of NSCLC post resection
• Indications for NSCLC resection
• Pleural Effusion in NSCLC: staging, prognosis and treatment
• Histologic subtypes of Lung cancer
• Para neoplastic syndromes in Lung cancer
• Erlotinib /TKI in NSCLC: Indication and toxicity
• SCLC: Staging and treatment
• Role of PCI in SCLC
Question # 7
• A 55 year old female is diagnosed with a descending colon adenocarcinoma
without obstruction. Pathology after hemicolectomy reveals 1 of 17 lymph
nodes is positive for metastatic carcinoma. Imaging reveals no evidence of
distant disease and a 3 week post op CEA level is 2.6. What would you
advice
• A: Surveillance with clinico-radiographic and biochemical parameters
• B: Adjuvant treatment with 6 months of FOLFOX chemotherapy
• C: Adjuvant radiation treatment after chemotherapy
• D: Targeted therapy with Bevacizumab or Cetuximab
Explanation for question # 7
Answer B
PRINCIPLE TESTED:
• Recognize and treat stage III colon cancer appropriately
• Node positive colon cancer defines stage III disease
• Adjuvant chemotherapy is indicated
• BUT adjuvant XRT is not indicated in colon cancer
(XRT is often indicated in rectal cancer)
• Cure rates in stage III colon cancer can go from 50% after surgery alone to
70% with adjuvant chemotherapy and hence surveillance is not an option
• Bevacizumab ( anti VEGF antibody) and Cetuximab ( anti EGFR antibody)
are indicated in the treatment of stage IV setting only
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Colorectal Cancer
Clinical Features
• R sided vs L sided colon cancer
• Right sided tumors = silent, fewer symptoms and diagnosed at a later stage
• Right sided tumors = non specific symptoms, vague abdominal pain,
iron deficiency anemia and wt loss
• Left side tumors present with alterations of bowel habits and blood per
rectum more often than right sided tumors
• HNPCC presents more often with right sided tumors,
have MSI, have a better prognosis, despite resistance to 5FU
Colon Cancer Treatment
Surgery is curative in the early stages of colon cancer
Complete colonoscopy should be done prior to surgery to r/o synchronous lesions
proximally
Stage I and Stage II cancer:
No adjuvant chemotherapy
High risk Stage II needs adjuvant chemotherapy
(High risk = Obstruction/ Perforation/ Lympho-vascular invasion)
Stage III (node pos) cancer:
Adjuvant chemotherapy
Stage IV colon cancer:
Non curative chemotherapy
Colon Cancer Prognosis
• Stage I: 90% 5 yr survival with surgery alone
• Stage II: 75% 5 yr survival with surgery alone
• Stage III: 50% 5 yr survival with surgery alone 70% with chemo
• Stage IV:
Untreated median survival
< 6 months
• Stage IV:
with 5FU-Leucovorin median survival
= 12 months
• Stage IV:
with FOLFOX /FOLFIRI median survival = 18 months
• FOLFOX/ FOLFIRI+ targeted therapy median survival = 24 months
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Question # 8
• Which of the following is not a risk factor for the development of
squamous cell carcinoma of the esophagus
• A: Tobacco / alcohol
• B: Obesity/ gastro esophageal reflux disease
• C: Ingestion of hot tea
• D: Achalasia
Explanation for Question # 8
Answer B
• PRINCIPLE TESTED:
• Esophageal carcinoma histologic subtypes, risk factors
• See next slide for details
Esophageal carcinoma
Squamous cell carcinoma
Adenocarcinoma
•
•
40-45% of all esophageal cancers
Upper and mid third of esophagus
•
•
60% of all esophageal cancers in US
Distal third of esophagus
•
•
•
•
•
Smoking-ETOH additive risk factors
Hot tea, ingestion of lye
Radiation strictures
Achalasia
Webs; Plummer Vinson syndrome
•
•
•
•
Chronic gastric reflux
Gastric metaplasia-Barrett’s
esophagus
Obesity
White males
•
Incidence in the US is decreasing
•
Incidence has increased dramatically
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Esophageal Carcinoma
Treatment
• Poor prognosis: fewer than 10% are alive 5 years after diagnosis
• Surgical resection is possible in only 45% of cases of which 20% are alive
at 5 years after successful total resection
• XRT efficacy for squamous cell carcinoma is similar to radical surgery
• Concurrent chemo-XRT can be curative for a group of patients and is the
approach of choice for upper third esophageal squamous cell carcinomas
• Lower esophageal/ GE junction tumors could be treated with protocols
similar to gastric adenocarcinoma
• In a fit patient TRI-MODALITY treatment offers the best chances of cure
Question # 9
• A 63 year old white male who has not seen a physician in many years
presents with dyspepsia and upper abdominal discomfort of 3-4 months
duration. He mentions that he has been in good health otherwise and
despite erratic meal habits as part of his backpacking lifestyle he has never
suffered from acid peptic disease. No h/o hematemesis or blood per rectum
but he has noted weight loss despite an adequate appetite. An EGD as part
of work up reveals a 2.5 cm greater curvature gastric ulcer positive for
adenocarcinoma on biopsy. A CT abdomen reveals multiple liver lesions
and a biopsy has been done. Which of the following tests is appropriate
•
•
•
•
A: Endoscopic Ultrasound
B: PET-CT
C: HER-2 testing on liver biopsy
D: Tumor marker CA 19-9
Explanation for Question # 9
• PRINCIPLE TESTED
• 10 % Metastatic gastric carcinoma is HER-2 positive and amenable to
manipulation with targeted therapy
• An endoscopic US is valuable in determining resectable gastric cancer
• Once metastatic disease is established the value of a PET-CT as a staging
tool is limited
• CA 19-9 is not typically elevated in gastric cancer
• See subsequent slides for details
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Gastric cancer subtypes
– Adenocarcinoma
– Gastric lymphoma
• MALT lymphomas: H.Pylori treatment is curative in 75% of tumors
• Large cell lymphomas: R-CHOP +/- surgery or XRT
– Sarcoma: GIST (Gastrointestinal stromal tumors)
•
•
•
•
Ulceration and bleeding on presentation
c-kit mutation positive, CD 117 positive
Size of tumor, anatomic location, mitotic rate and metastasis prognosticate
Imatinib (Gleevec) inhibits c-kit tyrosine kinase and is used in the adjuvant &
metastatic setting
• Sunitinib (Sutent) is another oral TKI used as second line agent.
– Carcinoid
Gastric Cancer Risk Factors
Age,
Male sex,
African American ethnicity
Gastric adenomatous polyps
Menetrier’s disease
Helicobacter Pylori infection
Smoking
Lower socio economic strata,
High nitrate content food
Family history of gastric cancer
FAP, HNPCC, BRCA-2
Partial gastrectomy for peptic ulcer
disease
Pernicious anemia
Chronic atrophic gastritis
Intestinal metaplasia
Gastric Cancer
Diagnosis & Treatment
Endoscopy accuracy 95% vs Barium studies 75%
Endoscopic Ultrasound (EUS) evaluates depth of invasion and regional
involvement
25-30% are resectable tumors: 5yr OS = 58%
Mucosal and submucosal disease: 5yr OS = 80%
Metastatic disease:
5yr OS = 23%
Adjuvant Chemo (5FU)+RT is standard of care
Peri operative chemo with ECF is an alternative for resectable disease
HER- 2 testing and treatment with trastuzumab in metastatic setting
Monitor Vit-B12, Iron, Folate and Calcium post gastrectomy
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Question #10
• A 55 year old male presents with dyspnea, weight gain and abdominal
distension. Abdominal exam reveals flanks are full, dilated veins over the
anterior abdominal wall and multiple spider angiomas. An abdominal US
reveals ascites, cirrhotic appearing liver with two large lesions in the right
lobe of the liver. Which of the following is the appropriate diagnostic test.
• A: PET-CT
• B: Alfa feto protein level
• C: Triple phase contrast CT
• D: CT guided liver biopsy
Explanation for question #10
Answer C
• PRINCIPLE TESTED:
• Diagnosis of hepatocellular carcinoma does NOT require a biopsy
• An alfa fetoprotein level is no longer a requisite for the diagnosis of HCC
• A PET-CT is of limited value in HCC
• The diagnosis of HCC usually is in the setting of chronic liver disease
• See subsequent slides for details
Hepatocellular carcinoma
Risk factors
Common risk factors
Unusual risk factors
•
•
•
•
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•
•
•
•
•
•
Cirrhosis- any cause
Hepatitis B or C infection
Chronic alcohol use
NASH
Aflatoxin B1
Primary biliary cirrhosis
Hemochromatosis
Alfa-1 antitrypsin deficiency
Wilson’s disease
PCT
Hereditary tyrosinemia
Citrullinemia
Glycogen storage disorder
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Hepatocellular carcinoma
Presentation
Symptoms
• Abdominal pain:
• Elevated LFT’S:
• No symptoms:
• Weight loss:
• Anorexia:
• Malaise:
• Routine CT:
• Cirrhosis sx:
Characteristics
40%
24%
24%
20%
11%
15%
17%
18%
• Age
• M:F
• Cirrhosis
56 yrs
3:1
81%
• Hepatic tumor characteristics
–
–
–
–
–
–
1=
20%
2=
25%
3 or more 65%
Unilobar= 25%
Bilobar= 75%
Portal vein invasion= 75%
Hepatocellular carcinoma
Treatment
• Early stage disease
–
–
–
–
–
Resection
Local Ablation Strategies: RFA
Local Injection therapy: ethanol
Transplantation
Adjuvant chemotherapy is not beneficial
• Advanced stage
– Transplantation in select patients
– TACE
– Sorafenib: Multi kinase inhibitor; median overall survival = 6 months
Question #11
• A 55 year old sedentary white female has noted vague abdominal pain with
radiation to the back. She usually weighs 285 pounds but has lost 15
pounds in the last 4 months as a result of a low calorie diet. She was
diagnosed with 2 episodes of lower extremity DVT and a CT PE protocol
recently ruled out PE but revealed a 0.9 cm cystic lesion in the body of the
pancreas. An ERCP and washings reveals atypical cells. What is the
diagnostic intervention in this patient?
•
•
•
•
A: MRCP
B: Endoscopic Ultrasound
C: CA 19-9 tumor marker
D: Whipple’s resection
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Explanation to question #11
Answer D
• PRINCIPLE TESTED:
• Pancreatic cancer is difficult to diagnose, often diagnosed late and may
need an aggressive diagnostic and therapeutic intervention to succeed
•
•
•
•
•
The diagnosis may be made with….
CT Pancreas protocol
Endoscopic Ultrasound and biopsy
MRCP
ERCP
• Resectability has to be assessed and eventually a resection with final path
offers the final diagnosis
Pancreatic Cancer - Introduction
Overview
Risk Factors
4th leading cancer death
Resectable
Locally advanced
Metastatic
Jaundice
Abdominal pain
Weight loss
= 25%
= 25%
= 50%
• Smoking
• Obesity
• Chronic Pancreatitis
•
•
•
•
•
•
Peutz Jeghers
FAP
HNPCC
BRCA-2
VHL syndrome
DM?
Pancreatic Cancer - Diagnosis
Clinical syndromes
Diagnostics
• Trousseau’s syndrome
•
•
•
•
•
•
• Courvoisier’s sign
• Virchow’s node
US
CT Pancreas protocol
ERCP
MRCP
Endoscopic US
Pathology
– Adenocarcinoma
– Neuroendocrine
– Islet cell tumor
• CA 19-9
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Pancreatic Cancer - Prognosis
• 5yr OS all pts
=5%
• 5yr OS post resection =20%
• Median OS
– Metastatic
= 6 months
– Locally advanced = 8-10 mon
– Resected
= 15 mon  20 mon
• Unresectable
– Distant mets
– Celiac artery or SMA inolved
– Portal or SMV occlusion
Pancreatic Cancer - Treatment
• Resectable
Whipple’s procedure followed by
adjuvant chemotherapy vs chemo-XRT ( both 5-FU based )
• Borderline Resectable
Neoadjuvant chemo +/- XRT followed by surgery
• Locally Advanced
Concurrent chemo-XRT in a definitive fashion
• Metastatic
– Gemcitabine
– FOLFIRINOX
– Abraxane + Gemcitabine
Section II Review
Hepato-Biliary & GI Oncology
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Adjuvant treatment of stage III colon cancer and its toxicity
HNPCC: Hereditary Non Polyposis Colon Cancer
Esophageal Carcinoma: subtypes, risk factors and treatment
Gastric cancer: MALT lymphoma, GIST, carcinoid
Treatment of Gastric cancer including HER2 positive disease
Neo adjuvant chemo radiation in rectal cancer
Definitive chemo radiation is curative in anal cancer
Diagnosis of Hepatocellular carcinoma without a biopsy
Local and surgical treatments of hepatocellular carcinoma
Sorafenib in metastatic hepatocellular carcinoma
Pancreatic cancer diagnostic challenges
Neo adjuvant chemo +/- radiation in borderline resectable pancreatic cancer
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Question #12
• A 38 year old lady patient is in your office very concerned that her aunt
aged 66 was diagnosed with aggressive HER-2 positive stage III invasive
ductal carcinoma of the breast. While there is no other history of breast
cancer in the family, there is a strong history of colo-rectal cancer amongst
her relatives with a first cousin diagnosed at age 29. Which of the
following recommendations is appropriate based on current USPSTF
guidelines
•
•
•
•
A: Biennial mammogram starting at age 50 and BRCA testing
B: Biennial mammogram starting at age 50 but do not test BRCA
C: Annual MRI starting at age 40 and BRCA testing
D: Annual MRI breast starting at age 40 but do not test BRCA
Explanation for question # 12
Answer: B
PRINCIPLE TESTED:
Breast cancer screening
• 90% of breast cancers are sporadic cancers and only 10% are inherited
• Risk of BRCA is increased with multiple first degree relatives with history
of breast or ovarian cancer and a younger age at diagnosis
• Test BRCA mutation in the affected individual first
• The family in question #7 may harbor the HNPCC gene
• GUIDELINES FROM USPSTF
• Start biennial screening with mammograms at age 50 for average risk
• No benefit to teaching self breast exams
Question # 13
• A 67 year old female is considering treatment for node positive, ER+ and
HER-2+ invasive lobular carcinoma of the left breast. She underwent a
lumpectomy with a 1 of 2 sentinel lymph nodes positive for a micromet.
Which of the following modalities/agents is safe in the setting of
cardiomyopathy
•
•
•
•
A: Adriamycin + Cytoxan  Taxol + HerceptinAnastrozole
B: XRT ( Radiation) followed by Anastrozole
C: Trastuzumab followed by Anastrozole
D: Anastrozole only
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Explanation for question # 13
Answer C
• PRINCIPLE TESTED:
Treatment of node positive breast cancer and its toxicity
•
•
•
•
•
•
Criteria for adjuvant treatment in breast cancer
Node positive disease
Tumor size > 2 cm in ER+ breast cancer ?
Tumor size 1-2 cm in ER+ breast cancer with high oncotype score
Tumor size > 1cm in triple negative breast cancer
Tumor size > 1cm in HER-2 positive breast cancer
• XRT indicated after lumpectomy in age < 70
• XRT indicated after mastectomy in node positive breast cancer
Reasons to treat Breast Cancer with
adjuvant chemotherapy
• Strong Indications
– Node positive breast cancer
– Triple negative breast cancer ( > 1cm in size)
– HER-2 positive breast cancer ( > 1cm in size)
• Moderate Indications
– Large tumors ( > >2 cm)
– Nottingham Grade III
– Younger women
• ONCOTYPE-DX for 1-2 cm, node negative, ER/PR + cancer
Breast Cancer Treatment I
Local treatment:
Breast Conserving Treatment:
SLN negative:
Lumpectomy + XRT = MRM
Lumpectomy  XRT
no further axillary node dissection
Adjuvant treatment
Chemotherapy:
Endocrine (ER +):
AI:
Targeted (Her-2+):
Adriamycin/CytoxanTaxane
Tamoxifen, Aromatase inhibitors
postmenopausal patients only
Trastuzumab (Herceptin)
Oncotype DX:
High risk gene signature to decide
chemotx in early stage breast ca.
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Question # 14
• A 47 year old premenopausal lady presents with metastatic breast cancer.
The tumor characteristics reveal grade III Nottingham histology, ER
strongly positive and HER-2 negative. A PET-CT reveals multiple bony
osteolytic lesions and 2 small liver lesions which on biopsy are confirmed
as metastatic adenocarcinoma. She feels well but is understandably anxious
to start treatment. The next appropriate intervention is
•
•
•
•
A: Weekly Taxol chemotherapy followed by Tamoxifen at progression
B: Multi agent chemotherapy x 6 months followed by Anastrozole (AI)
C: Anastrozole alone as single agent
D: Tamoxifen alone as single agent
Explanation to question # 14
Answer D
• PRINCIPLE TESTED:
First line treatment for ER + metastatic breast cancer without visceral
crisis
•
•
•
•
•
Premenopausal lady with invasive lobular carcinoma, ER+
Modest sized tumor… But…….
Multiple nodes positive, large nodal metastasis, extra nodal extension
Staging work up reveals metastatic disease
In hormone sensitive metastatic breast cancer treat with endocrine
agents whenever possible first
• Aromatase inhibitors can only be used in postmenopausal patients
• Tamoxifen can be used in pre and postmenopausal patients
Breast Cancer Treatment II
Neo Adjuvant treatment
LABC (locally advanced breast cancer)
Metastatic Disease:
Bone vs CNS vs Visceral
Endocrine Rx:
Chemotherapy:
Chemotherapy:
Bisphosphonates:
ER + and no visceral crisis (AI preferred)
ER – (negative) disease
Hormone refractory
Visceral crisis
single agent preferred
bony mets or hypercalcemia
treats pain, reduces fractures
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Metastatic Breast Cancer
Goals of treatment
Noncurative
•
•
•
•
Slow progression of disease
Prolong suvival
Improve quality of life
Minimize treatment related toxicity
Question #15
•
A 34 year woman is in your office for a Pap smear and routine health
maintenance visit. She wishes to discuss breast cancer risk factors. Which
of the following statements is incorrect?
• A: Sporadic breast cancer is thrice as common as familial breast cancer
• B: Combination oral contraceptive pills (OCP) are a greater risk than
replacement premarin (after a hysterectomy)
• C: Alcohol intake is a risk factor for breast cancer development
• D: A higher body mass index in post menopausal women is a risk factor
Explanation for question #15
Answer A
• PRINCIPLE TESTED
• Risk factors for breast cancer development
• Heredo familial breast cancer accounts for only 10% of all breast cancer
• Upto half of heredo familial breast cancer is related to BRCA I and II
• Sporadic breast cancer accounts for 90% of breast cancer
• Age is the commonest risk factor for breast cancer with the incidence
peaking in the late 60’s and early 70’s
• Estrogen is a risk factor for breast cancer development.
• Combination OCP are a greater risk than estrogen alone
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Breast Cancer
Genetic syndromes
Test the pt with path proven breast cancer and not the unaffected family member in you office for consultation
Question #16
• Which of the following statements about sentinel lymph node biopsy in
breast cancer treatment is incorrect
• A: All invasive breast cancers require a SLN biopsy irrespective of size or
histology
• B: DCIS would require a SLN biopsy only if the size is over 2.0 cm
• C: Some positive SLN biopsies do not require a completion axillary
dissection (ALND)
• D: A SLN biopsy can be done in pregnant women
Explanation for question #16
Answer B
• PRINCIPLE TESTED:
• Sentinel lymph node biopsy in breast cancer
• Indications, prognostic significance
• All invasive breast carcinomas do require a sentinel lymph node biopsy
• In situ carcinoma (DCIS and LCIS) does not require a SLN biopsy
• A SLN biopsy is required in a melanoma if the lesion is > 1mm in depth
• A SLN biopsy can be done in pregnant women with the radio colloid but
methylene blue cannot be used.
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Question #17
• Which of the following agents cannot be used for breast cancer prevention
based on the Gail score
• A: Tamoxifen
• B: Anastrozole
• C: Raloxifene
• D: Bisphosphonates
Explanation for question # 17
Answer C
• PRINCIPLE TESTED:
• Breast cancer prevention
• The breast cancer prevention trials (BCPT) demonstrated that Tamoxifen
and Raloxifene (Evista) have a role in chemoprophylaxis
• Anastrozole does have data from prevention trials but Letrozole does not
• Bisphosphonates have no robust data in breast cancer prevention
Question #18
• Which of the following is not an expected side effect of breast cancer
treatment
• A: Cardiomyopathy
• B: Neuropathy
• C: PML (progressive multifocal leukoencephalopathy)
• D: Osteoporosis
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Explanation to question # 18
Answer C
• PRINCIPLE TESTED
• Toxicity of breast cancer treatment
• All the side effects listed could be seen in breast cancer treatment
• EXCEPT
• Progressive multifocal leuco encephalopathy which is noted with
Rituximab
Breast Cancer
Treatment related Toxicity
• Axillary node dissection:
Lymphedema
• Chest wall XRT:
second malignancy (NSCLC)
• Tamoxifen:
• Aromatase Inhibitors:
DVT, Endometrial cancer (1%)
(protective toward bone health)
osteoporosis
• Herceptin:
• Adriamycin:
• Taxanes:
cardiotoxicity (EF q 3 months)
cardiotoxicity (EF before & after )
neuropathy
Section III Review
Breast Cancer
• Breast Cancer screening guidelines
• Risk factors for Breast cancer development and hereditary syndromes
• Breast cancer chemo prevention
• Adjuvant chemotherapy in breast cancer: Indication and toxicity
• Adjuvant Endocrine treatment, Indication and toxicity
• Sentinel lymph node biopsy
• Metastatic breast cancer: Evaluation, prognosis, treatment and toxicity
• Cardiac toxicity of breast cancer treatments
• Endocrine treatment toxicity
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Question #19
• A 72 year old male with a h/o IgA myeloma is currently on maintenance
Lenalidomide after an autologous HSCT. He presents to the ED with
fatigue, increased thirst and significant urination. He mentions that his
oncologist was planning to switch therapy after evaluating his recent serum
free light chain assay. Labs have been drawn and are pending. An EKG
done reveals tall T waves with QRS widening. Which of the following is
not indicated in the treatment of his acute condition
•
•
•
•
A: I.V fluids with normal saline
B: I.V Velcade
C: I.V Bisphosphonates
D: SQ Calcitonin
Explanation to Question #19
Answer B
• PRINCIPLE TESTED:
• Hypercalcemia as an oncologic emergency and its treatment
• See subsequent slides
Treatment of Hypercalcemia
• Depends on:
– 1. Level of calcium
– Mild Hypercalcemia;
– Mod Hypercalcemia;
– Sev Hypercalcemia;
< 12 mg/dl:
12-14 mg/dl:
> 14 mg/dl:
Fluids
Bisphosphonates
Calcitonin
– 2. Rate of rise of calcium
– 3. Symptoms and Signs
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Treatment of Hypercalcemia
Saline Hydration
 Initial rate 200-400 ml/hr and then to maintain urine output of 100 to
150 ml/h
 Loop Diuretics only after volume repleted
20-40 mg Furosemide as needed (disfavor?)
BISPHOSPHONATES
 Zoledronic acid , Pamidronate
Calcitonin; lasts 48hrs. Tachyphylaxis develops.
 2-8 IU/kg sc/im q 6-12 hrs
Glucocorticoids; Prednisone 40-100 mg in 4 divided doses p.o
Gallium Nitrate; effective even if PTHrP increased
Treatment of Hypercalcemia
• BISPHOSPHONATES
• Adsorb to bone hydroxy apatite and inhibit calcium release from osteoclast
mediated bone resorption
• Pamidronate; 90 mg iv over 2-4 hrs
– Takes 1-2 days to take effect
– Lasts 10-18 days. Do not redose for at least 7 days
– May be used in renal insufficiency. Dose adjust
• Zoledronic acid; 4 mg iv over 15 min
– Median duration of calcium control = 32-43 days
– Renal toxicity esp with 8 mg dose
• Toxicity; Osteonecrosis, flu sx, bone pain, renal failure
Question # 20
• A 29 year old white male presents with 2 day history of headache when he
lies down and improved when leans forward. He denies any other
symptoms. His exam is remarkable for a distended jugular vein and facial
puffiness but otherwise unremarkable. A CXR reveals a large mediastinal
mass and work up is instituted. Which of the following is not a modality of
treatment in this condition
•
•
•
•
A: Surgery/ Resection
B: SVC stent
C: Chemotherapy
D: Radiation
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Explanation for question # 20
Answer B
• PRINCIPLE TESTED:
• SVC syndrome in malignancy, varied etiologies
treatment schema depends on the etiology
• SVC stent is appropriate in the non malignant SVC syndrome such as with
a thrombus
• See subsequent slides
SVC Syndrome - Malignant causes
Tumor Type
Incidence
Clinical Features
• NSCLC;
• SCLC
50% (43-59)
22% (7-39)
smoking, age>50
smoking, age>50
• Lymphoma
• Met Cancer
12% (1-25)
9% (1-15)
LN+, age<65
h/o ca, Breast++
• Germ cell
• Thymoma
• Mesothelioma
3% (0-6)
2% (0-4)
1% (0-2)
young, male, tm+
CXR/CT, paraneoplastic
asbestos exposure
Symptoms & Signs - SVC syndrome
Sx / Sign
–
–
–
–
–
–
–
–
–
Facial Edema
Arm Edema
Dist Neck Veins
Dist Chest Veins
Facial Plethora
Visual Sx
Dyspnea
Cough
Hoarseness
Frequency %
82
46
63
53
20
2
54
54
17
Range %
60-100
14-75
27-86
38-67
13-23
0-3
23-74
38-70
15-20
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Management of SVC syndrome
• Raise the head end of the bed
• Steroids of ? benefit. May make pathology unclear
• CT Chest with contrast is diagnostic
• TREAT THE UNDERLYING CAUSE
• Chemotherapy
– Lymphoma, Germ cell tumor, Small cell lung cancer
• Radiation Treatment
– Non small cell lung cancer, Small cell Lung cancer, Lymphoma,
metastatic disease
• Surgery
– Thymoma
Question #21
• A 32 year male is admitted with stridor, headache and facial puffiness.
After emergent ENT intervention his work up revealed a large mediastinal
mass and biopsy confirmed a lymphoblastic lymphoma. After full staging
and work up multiagent chemotherapy is instituted in the ICU. On day 3 of
treatment the patient develops seizures and torsades. Which of the
following tests is diagnostic of his condition
•
•
•
•
A: CSF cytology for meningeal lymphoma
B: CBC, Blood cultures and CSF Glucose
C: Serum creatinine, Phosphorous and Calcium
D: Serum magnesium, Potassium and EKG
Explanation for question #21
Answer C
• PRINCIPLE TESTED:
• Recognize Tumor lysis syndrome and the scenario it is frequently seen
in.
• See subsequent slides
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TLS Definition
• 1993 Hande-Garrow classification system distinguished between clinical
and lab definitions
• Cairo-Bishop definition 2004; specific lab values
– Any 2 or more lab values
– Uric Acid: > 8 mg/dl
(or) 25% increase from baseline
– Potassium: > 6.0 mmol/L (or) 25% increase from baseline
– Phosphate: >4.5 mg/dl (or) 25% increase from baseline
– Calcium: <7 mg/dl
(or) 25% decrease from baseline
• CLINICAL TLS:
Lab+ any one of following:
s-creat >1.5 uln, arrhythmia, seizure or sudden death
Tumor Lysis Syndrome TLS
Risk factors
Treatment/Prophylaxis
•
•
•
•
• I.V fluids
Bulky disease
Proliferative rate
High wbc count
Chemo sensitive tumors
• Renal insufficiency
• Dehydration
• Hyperuricemia
• Allopurinol
• Rasburicase
• Dialysis
• Electrolyte management
Question #22
•
A 55 year old lady comes with a five week history of swelling of the left
arm and left shoulder with pain. Exam reveals a firm 3 cm left axillary
adenopathy. No breast lumps palpable bilaterally. No other adenopathy
noted. Bilateral MRI of the breast, Mammogram and CT
Chest/Abdomen/Pelvis is unrevealing. Core biopsy of the axillary node is
reported positive for malignancy pending final stains and path report.
Choose the correct intervention once path is confirmed.
•
•
•
•
A: Node excision followed by adjuvant interferonmelanoma surveillance
B: Left radical mastectomy, axillary dissection and adjuvant chemotherapy
C: Bone marrow biopsy followed by R-CHOP chemotherapy
D: XRT to left axilla followed by csurveillance and biopsy of future lesions
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Explanation for question #22
• PRINCIPLE TESTED:
• Recognize the entity Carcinoma of unknown primary
• Learn the work up for CUP and understand it’s a diagnosis of exclusion.
• See subsequent slide
Carcinoma of Unknown Primary
15-25% of patients with cancer of unknown primary (CUP) do not have a
primary site identified even at autopsy
Overall grim prognosis: poor response to cytotoxic therapy
Women, Unilateral axillary node with carcinoma
Upper cervical node- squamous cell ca
Young males, midline tumors
Peritoneal carcinomatosis + ascites
 Breast Ca
 Head and Neck Ca
 Germ cell tumor
 Ovarian Ca
Expert pathology review: including molecular studies
Immunohistochemistry: ER, TTF-1, HER-2, PSA, Mart-1, CK-7, CK-20
Tumor markers:
CEA, PSA, CA 19-9, AFP, HCG, LDH, CA 27-29
Immunophenotype:
CD20+, CD30+
Extensive radiographic and endoscopic evaluation
Cancer Screening I
USPSTF Guidelines
•
•
•
•
•
•
CERVICAL CANCER
Do not screen before the age of 21
Age 21-65 cytology every 3 years or
Age 30-65 cytology and HPV every 5 years
Do not screen after age 65 and 3 negative cytology in previous 10 years
Do not screen after hysterectomy and removal of cervix
•
•
•
•
•
LUNG CANCER
Low dose CT
Age 55-80
30 pack year h/o smoking
Active smoker or quit in last 15 years
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Cancer Screening II
USPSTF Guidelines
•
•
•
•
•
•
•
•
•
•
•
•
BREAST CANCER
Start screening age 50 with mammography (discuss ages 40-50)
Every 2 years
Do not endorse MRI breast in average risk
Do not endorse teaching self breast exams
Insufficient evidence for benefit or harm with clinical breast exam
COLORECTAL CANCER
Screen age 50-75
FOB (annual), Sigmoidoscopy or colonoscopy every 5 years
Does not endorse CT colonography/ stool DNA immunohistochemical test
PROSTATE CANCER
Do not screen with PSA regardless of age
Section IV Review
Miscellaneous
• Hypercalcemia: etiology, tests, treatment
• SVC syndrome: presentation, diagnosis and treatment
• Tumor lysis syndrome: recognize risk factors, prevention, diagnosis
• Spinal cord compression: low threshold to order MRI , steroids, XRT
• CNS mets (intracranial): Imaging, steroids, XRT
• Carcinoma of Unknown Primary metastasis patterns, diagnostics
• Cancer Screening
THANK YOU
&
GOOD LUCK
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