ONCOLOGY BOARD REVIEW. Most Common Solid Tumors TypeStagingPrimary RxAdjuvant RxSurveillance/...
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Transcript of ONCOLOGY BOARD REVIEW. Most Common Solid Tumors TypeStagingPrimary RxAdjuvant RxSurveillance/...
ONCOLOGY BOARD REVIEW
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM
Breast Cancer Staging
• Generally pathologic Staging, but clinical staging for neoadjuvant therapy.
• T4 are pts with “grave” prognostic signs (skin, chest wall, ulcer, inflammatory)
• N3 (supraclavicular nodes, Internal mammary nodes (Clinically staged)
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNMSurgery or
Surgery and XRT
Yes
Breast CancerAdjuvant Therapy
• Additional Therapy after all gross disease is removed.
• Options include Hormonal Therapy for ER positive disease, Chemotherapy for all patients (better for premenopausal), and Biologic therapy for 20-25% Her 2 overexpressors.
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes Yes
Breast CancerSurveillance/Screening
• Q year Mammogram starting age 40 saves lives
• BSE/CBE does not save lives, but is done
• Surveillance q year mammograms, bimanual exam (on tamoxifen) w/wo Ultrasound, baseline dexascan (AI), MUGA baseline then after anthracylcine rx, then after herceptin is complete
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic Rx
Breast CancerSystemic Therapy
• Therapy is based on Er status and Her 2 status.
• Er positive get hormonal therapy Her 2 postive get Herceptin
• Non organ threatening disease get either hormonal rx alone or Single Agent Rx in metastatic setting
• AI only for postmenopausal
Quiz 40 yo woman with breast ca 5 yrs ago rx with
lumpectomy and xrt and 3 months of chemotherapy. ER/PR neg, Her 2 pos. and presents with skin nodules back pain and lung nodules on xray. Biopsy of skin adenocarcinoma. How to Rx.?
A.)Hospice B.)Tamoxifen and AI C.) High dose
CT bone marrow tx D.)Trastuzumab and Taxane E.) Ovarian ablation plus and AI
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
Breast Cancer Genetics• 5-10% of women have inherited form of Breast
cancer (Ashkenazi Jewish women with 1%)• Three generation Pedigree• Penetrance is 40-80%• Most informative is one with known mutation and
with breast cancer• BRCA1 associated with Ovarian, BRCA2 is
found in male Breast CA• Consideration for prophylactic bilateral
mastectomy and oophorectomy and Genetic counseling
Quiz
• 65 yo woman sp MRM for 1 cm breast ca with er and pr positive and negative for Her 2. SLN negative. What next?
A.) xrt and tamoxifen
B.) xrt and Anastrazole
C.) Tamoxifen for 5 yrs
D.) TAmoxifen and anastrazole for 5 yrs.
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Colorectal CancerStaging
• Depth of invasion with T3 invading muscularis propria (stage II) and T4 invading adjacent structures
• N denotes nodes in pericolonic or rectal regions
• Rectal staged the same but below peritoneal reflection
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes
Colorectal CancerAdjuvant Rx
• Stage III colon (node positive) cancer OS benefit with 5FU based rx (oxaliplatin?)
• Stage II and III Rectal cancer rx with Chemo and radiation therapy
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes Yes
Colorectal CaSurveillance/Screening
• Vogelstein Model of progression of normal mucosa to cancer takes about 10 years
• FOBT yearly saves lives, Colonoscopy every 10 years except for high risk groups.
• Surveillance Colonoscopy one year after resection and then q 3-5 years
• CEA done but not required and CT scan every year for first 3 to 5 years
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
Colorectal Cancer
• Chemotherapy: 5 Fluorouracil {diarrhea, mucositis, myelosuppression (if bolus), Hand foot syndrome (if continuous infusion)}. Oxaliplatin (Neuropathy, cold induced Laryngospasm), Irinotecan (Pro-cholinergic side effects, diarrhea, myelosuppression)
• Biologics: Role is metastatic disease. Avastin (Bleeding, HTN), Cetuximab (infusion related side effects)
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
Colorectal CancerGenetics
• Incidence 148300 per year 56000 deaths• Familial Risk is 20% (>1 1st or 2nd degree)• 5-10% inherited in AD pattern• FAP and HNPCC (Age at onset HNPCC is
45 vs 63)• Proximal HNPCC and Distal FAP• Microsattelite instability (HNPCC MSH2
and MLH1) Very sensitive (negative test no need to do germ line assessment)
MSI/HNPCC
• 12 to 16% with MSI• Mutation in germ line is usually in non coding region,
thus, elongation or contraction of DNA has little effect.• Detection shows homozygosity in germ line but multiple
peaks in tumor• 70% proximal to splenic flexure• Endometrium, Ovary, Stomach, small bowel , pancreas
hepatobiliary, brain,upper uroephtielial, sebaceous deonma sebaceou ca keratacanthoma (Torres Syndrome)
• Adenoma to ca in 2-3 yrs (vs 8-10 yrs)• Surveillance age 20-25 with q 1 to 3 yrs colonoscopy,
screen for Ovary and Endometrial
Quiz
• 58 yo postmenopausal woman on HRT for 4 yrs. Has father died of heart disease, mother died of breast cancer, sister with breast cancer. She had biopsy 2 years go showing atypical hyperplasia. She is considering chemoprevention but is concerned about heart disease. You recommend:
• A.) HRT alone B.) HRT and Tamoxifen C.)DC HRT and start Tamoxifen D.) Change HRT to estrogen alone and add Tamoxifen
FAP/APC
• Cancer by age 40-50• Screening at at 10-12, and yearly• Age 20 sutotal colectomy with annual fu of remaining
rectum due to numerous polyps• Gastric, Duodenal, Periampullary CA, Desmoids
(induced by surgery).• Less common are papillary thyroid, sarcoma, pancreatic
ca, meulloblastomas• Penetrance is 100% except in 11307K mutation in
Ashkenazi Jews (10-20%)• Celecoxib and Sulindac decrease number of polyps and
delay surgery but still need screening
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
TNMProximity
Non Small Cell Lung CAStaging
• T3 invasion into chest wall or less than 2 cm from carina
• T4 invasion into major structures (SVC, Pericardium, Vertebral Body) or pleural effusion
• N1 Hilar nodes, N2 Mediastinal nodes, N3 contralateral Mediastinal or Hilar or Supraclavicular
• Stage III A is N2 disease, Stage IIIB T4 or N3
NEJM: 348:2500-2507,2003
Lung CancerStaging
Study: Prospective of Dx Accuracy of Integrated PET-CT,CT,PET, and PET plus CT.
METHODS: 50 pts with proven or suspected NSCLC and then histopathologic confirmation or one other radiologic modality
Results: PET-CT better vs others above (P=.001,P<.001,P=.013). Nodal staging better with PET-CT vs PET (p=.013)
Conclusions: Integrated PET-CT improves dx accuracy of staging in non-small cell lung ca.
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
TNMProximity
Surgery Yes
from NEJM: 352:2640-2642,2005
Non Small Cell Lung CancerAdjuvant
• Adjuvant systemic therapy indicated for NSCLC
• Stage IB to III seem to benefit
• Platinum based regimens are appropriate
Study N Rx Results P level Other
IALT 1867 CDDP vs Obs
44.5 vs 40.4 OS at 5 yrs
P<.03 FU 56 mo
St. I,II,III
JBR 10 482 CDDP + Navelbine vs obs
69 vs 54% at 5 yrs
P=.04 HR = .69
FU 5.1 yrs St. IB,II (no benefit in stage I)
CALGB 9633
344 Carbo taxol
71% vs 59% at 4 years
P=.018 St IB
ANITA 840 CDDP + Navlebine
51 vs 43% 5 yr OS
P= .013 FU 70 mo.St I,II,III
(no benefit in stage I
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
TNMProximity
Surgery Yes No ChemoSmall Molecule
Non Small Cell Lung CASystemic Rx
• Chemotherapy: Cisplatin (Neuropathy, Nephropathy, Nausea/vomiting), Carboplatin (Myelosuppression and Thrombocytopenia), Taxol (Neuropathy, Allergic Rx), Gemzar (Myelosuppression), Taxotere (3rd Spacing), Navelbine (Myelosuppression)
• Tarceva (EGFR TKI) Rash, Diarrhea
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
TNMProximity
Surgery Yes No ChemoSmall Molecule
Paraneoplastic
Non Small Cell Lung CAParaneoplastic Syndromes
• Squamous Cell CA : Hypercalcemia
• Adenocarcinoma: Clubbing and Hypertrophic Osteoarthropathy
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
TNMProximity
Surgery Yes No ChemoSmall Molecule
Paraneoplastic
Limited orExtensive
Chemo or Chemo XRT NA No Chemo Paraneoplastic
Small Cell Lung Cancer• Staging includes Bone scan and Brain
scan if limited
• Cisplatin and Etoposide (WBC and Platelets and AML) with xrt for LS and Chemo alone for ES
• Eaton Lambert, SIADH, Perhipheral Neuropathy
Quiz
• 70 yo man with 80 pk yr tobacco presents with chronic cough and a 3 cm perihilar mass. CT scan shows two nodules in liver and PET shows no uptake in liver but uptake in mass. Bronch positive for cancer.What next?
• A.) xrt B.)Chemotherapy C.) CT guided liver biopsy D) CEA E.) Surgery
Quiz
68 yo man with 60 pk yr tobacco evaluated for hemoptysis. CXR shows right hilar mass and mediastinal widening. Bronch shows small cell. He has low sodium and SIADH. Rest of workup shows no disease. How do you rx?
A.) Surgery followed by chemo B.) XRT followed by chemo C.) Chemotherapy alone D.)XRT and concurrent chemo E.) Chemo followed by xrt
Most Common Solid TumorsType Staging Primary Rx Adjuvant Rx Surveillance/
ScreeningSystemic Rx Misc
Breast
Colorectal
Lung (NSCL)
Lung (SCLC)
Prostate
TNM Surgery Yes YesHormonal
ChemoBiologic
BRCA 1BRCA 2
LCISDCIS
TNMDepth
Surgery Yes YesChemoBiologic
FAPHNPCC
TNMProximity
Surgery Yes No ChemoSmall Molecule
Paraneoplastic
Limited orExtensive
Chemo or Chemo XRT NA No Chemo Paraneoplastic
TNMClinical
Surgery orXRT or
ObservationNA
PSA?DRE?
HormonalChemo
chemoprev
NEJM:352,1977-1984, 2005
Prostate CancerTreatment
N = 695 (FU was 8.2 years)
Design: Randomized study of pts less than 75 with localized prostate cancer to radical prostatectomy or observation
Pts: Median age 64, T1 and T2, GS 5-6 was 47% of population, GS 7 was 22%, GS 8-10 was 4-6%, Mean PSA 12-13.
Results: RR 0.56 (CI .36-.88) for RP for death from cancer. OS was .74 (CI.56-.99) or 5% absolute at 10 years. Local progression 19-25% lower risk (RR.33) and Distant mets 8% (RR .60)
Conclusion: RP decreases overall disease specific and overall mortality by a modest amount. Substantial benefit for distant mets and local tumor progression
NEJM: 350: 2239-2246, 2004
PROSTATE CANCERSCREENING
N = 2950Method: subgroup analysis of men who never had a PSA
more than 4 ng/ml or abnormal DRE who had a final PSA determination and underwent biopsy after 7 years on study in PCPT randomizing 18,882 men to placebo or Finasteride 5mg.
Results: 15% had prostate ca, 6.6% with psa 0.5, 10% w/PSA .5 to 1,17% w/PSA 1.1 to 2,23.9% w PSA 2.1-3, and 26.9 w/PSA 3.1-4.0. High grade cancer in 12.5% with PSA 0.5 and 25% PSA 3.1-4.0.
Conclusions: Biopsy detected prostate cancer not rare among men with normal PSA (4 or less). High grade cancers also are detected.
349:215 - 224, 2003
Prostate CancerPrevention with Proscar
N= 18882 55 or olderMethods: Normal DRE and PSA randomized to
Finasteride 5 mg vs Placebo.Results: Finasteride decreased incidence of
prostate ca from 24.4 to 18.4 percent (24.8% reduction CI 18.6 to 30.6) p<.001. High grade tumors higher in finasteride group 37 vs 22% (p<.001)
Conclusions: Delays appearance of prostate ca but benefit may be nullified by risk of side effects and increased risk of high grade cancer.
Quiz
45 yo presents with 2 cm palpable axillary node on right. Resection shows adenocarcinoma. CT and MRI show no other sites of disease. How do you manage?
A.) Breast ca is most likely dx and rx as such B.) Lung ca is most likely and rx as such C.) All disease resected no more rx D.) Radiation therapy to axilla and breast is appropriate.
Group IHormonally Related or Genetic
SyndromeType Staging Primary
RxAdjuvant Rx
Screeining
Systemic Rx
Misc
Breast TNM Surgery Yes Yes Chemo, Hormonal, Bioloigic
LCIS, DCIS, Genetic Syndromes
Endometrial
Ovarian
Colorectal TNM Surgery Yes Yes Chemo, Biologic
Genetic Syndromes
Prostate TNM Surg, XRT, or Obs
NA PSA?
DRE?
Hormonal, Chemo
Chemoprev
TNMProximity
DepthSurgery No No Hormonal
Chemo BRCA1
TNM/FIGOSurgical Lap
Surgery and Debulking
Mostly NASome Yes
No ScreenCA 125 for FU
Chemo andIP Chemo BRCA1
Group IIForegut, Smoking, or Environment related
Type Staging Primary Rx
Adjuvant Rx
Screening Systemic Rx
Misc
Lung TNM
Proximity
Surgery Yes No Chemo Paraneoplastic
Gastric
Pancreatic
Esophogus
Bladder
TNMDepth
Surgery No No Chemo
TNMProximity
Surgery No No ChemoBiologic?
TNMDepth
Surgery No? No Chemo Barrets?
TNMDepth
Surgery No? NoChemoImmuno
Ureteral
Group III Squamous Cell Rx with Chemo and XRT as Primary Rx
Type Staging Primary Rx
Adjuvant Rx
Screening Systemic Rx
Misc
Cervical
Anal
Head and Neck
TNMDepth Extent
SurgeryOr Chemo
XRTNo Yes Chemo HPV?
TNMSize
Chemo+ XRT No No
Chemo(MMC)
HPV?
TNMDepth,Size
SurgeryOr
XRT +-Chemo
No? NoChemoBiologic
NPC/EBVEGFR MCAWith XRT?
Group IV Curable in Metastatic Setting
Type Staging Primary Rx
Adjuvant Rx
Screening Systemic Rx
Misc
Germ Cell IGCCC3 stages
Surgery plus XRT or Chemo NA? No Chemo
NSGCT AFP HCGSeminoma HCG
XRTResidual Masses
Group VIncurable or Poor Systemic Rx
Type Staging Primary Rx
Adjuvant Rx
Screeining
Systemic Rx
Misc
Brain
Hepatic
Melanoma
Renal Cell
Adult Sarcoma
Grade Surgery NA No ChemoAA and GBM
Incurable,OLIGO chemo
xrt
TNMSize
Extent
TNMGrade
SizeSurgery
Bone and Rhabdo
onlyNo Chemo
X ray for EwingAnd Osteosarc
Cytogentic11:22, X:18
TNMExtension
Surgery No NoBiologic
TKI?Polycythemia
TNMDepth
Surgery No? NoChemoBiologic
Sentinel nodFamilial Synd
SurgeryTransplant? No
AFP?US?
ChemoTKI?
Hep B
Long Term Complications of Chemotherapy
Neuropathy
Second Malignancies
Pulmonary Toxicity
Osteoporosis
Fertility
Long Term Complications Radiation Therapy
Second Malignancies
Proctitis
Endocrine
Xerostomia
Quiz
68 yo woman with hx of lumpectomy and breast xrt and tamoxifen for er pos 1 cm breast cancer node negative develops lump on chest wall. Biopsy shows fibrosarcoma. What is relationship between this and her treatment?
A.) Related to original CA B.) Related to xrt C.) Related to tamoxifen D.) Not related to original cancer or treatment
Long Term ComplicationsHormonal Therapy
Second Malignancies
Osteoporosis
Long Term ComplicationsSurgery
Breast : Lymphedema, Neuropathy
Gastrectomy: Nutritional Deficiency
APR: Long term ostomy issues
Prostatectomy: Urinary Incontinence, Impotence
RPLND: Retrograde ejaculation
NEJM: 352:2714-2720,2005
Lung Cancer Screening
• No randomized studies showing survival benefit• ELCAP study of 1000 pts over 60 with 10 pack
yrs found 233 non calcified nodules by CT and 68 by CXR (alone?) and 27 of CT scan detected were malignant and 7 by CXR were malignant. Stage I in 23 of CT pts and 4 of CXR pts.Thus dx early disease
• Ongoing randomized studies by NCI and European studies are pending.
• Length time bias (biology), Lead time bias (measurement), Unnecessary procedures