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Philippine Society of Medical OncologyUnit 1418, 14/F, North Tower, Cathedral Heights Bldg., St. Luke’s Medical CenterE. Rodriguez Sr. Avenue, Quezon City 1099, PhilippinesTelefax: (632) 721-9326/ 723-0101 local 5318
Governing Council 2005-2006
PresidentVice President
SecretaryTreasurer
Immediate Past President
Jasmin V. Reyes-Igama, M.D.Gerardo H. Cornelio, M.D.Maria Belen E. Tamayo, M.D.Agnes S. Evangelista-Gorospe, M.D.
Gracieux Y. Fernando, M.D.
Council MembersAdonis A. Guancia, M.D.Dennis M. Tudtud, M.D.
Ma. Noemi L. Alsay-Uy, M.D.
Advisory CouncilAntonio H. Villalon, M.D.
Valorie F. Chan, M.D.Corazon A. Ngelangel, M.D.
Officers
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The following practice guidelines are the top two cancers in the Philippines. Lung Cancer, followed by Breast Cancer.
These guidelines were adapted from the NCCN (National Comprehensive Cancer Network) and was written and reviewed by the following: 2004-2005 Medical Oncology Fellows in training Philippine General Hospital Dr. Jose R. Reyes Memorial Medical Center St. Luke's Medical Center Sto Tomas University Hospital Veterans Memorial Medical Center PSMO Governing Council Medical Oncology Consultants
The Philippine Society of Medical Oncology, is presently in consultation with other societies dealing with cancer management. Thus we hope the next edition will contain a consensus of practice guidelines, agreed upon by all societies concerned, and to include all the Top Ten cancers in the Philippines.
Jasmin V. Reyes-Igama, M.D.PSMO President
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Algorithm for Breast Cancer
(+) Cancer? (C)
Breast CA Suspect (A)
Open biopsy (B)
Stage (D)
Refer
Stage O? LCIS? (E) Observation
DCIS
Lumpectomy with nodal sampling or
MRM
ER/PR +? (F)
Adjuvant Hormonal Treatment
Observe
Stage I or II?
Breast Conservation or MRM (G)
Go to Fig. C
Go to Fig. B
1
2
3 4 5 6 7
8 9
10
12 13
14
15 16
Y Y Y
Y
Y
N
N
N
N
N
FigureA
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Ax LN+? (H)
ER/PR+? (F)
Adjuvant chemotherapy + Hormonal
treatment
Pre-meno-pausal?
Menopausal
Adjuvant chemotherapy ± Hormonal
treatment
Adjuvant chemotherapy
(+) margin or (+) LN?
Adjuvant Radio-
therapy (I)
(+) margin or (+) LN?
Adjuvant Radio-therapy
Observe
Observe
Go to #10
Tumor size <0.5 cm or
0.6-1.0 cm or with favorable
prognostic factors?
Observe
Go to #2
Figureb
1 2 3 4 5
6 7 8
9 10 11
12 13
14
15
Y Y Y
Y
Y
Y
N
N
N N
N
N
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Palliative Chemotherapy/
Hormonal Therapy or BSC
Stage III? Operable? MRM
Neoadjuvant Chemotherapy
(J)
Chemotherapy with RT
ER/PR+? (F)
Adjuvant Chemo-
therapy ± Hormonal
Adjuvant RT to breast and regional
nodes
Adjuvant Chemo-therapy
Stage IV (K)
Palliative Surgery (F)
Palliative Radiotherapy or Best Supportive
Care (BSC)
Figurec
1 2 3 4 5
6 7
8
9
11
12 13 14
Y
N
Y
N
Y
N
Adjuvant RT to breast and regional
nodes
10
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Management of Breast Cancer
The management of breast cancer must be multi-disciplinary, interdisciplinary, with each discipline respecting the specialty expertise of the other, all for the benefit of the cancer patient.
(A) Most breast cancer (hard, painless, movable, then becomes fixed to the chest wall/skin, with/without nipple retraction) are found by palpation by the patient, her partner or her physician. As tumor site increases, the likelihood that distant metastasis has taken place rises. It is better to detect and treat early (asymptomatic <1 cm diameter tumor size). Mam-mography can detect very early <1 cm tumor mass and hence effective in screening.
(B) If total mastectomy is anticipated, it is best to con-firm the diagnosis with open biopsy. For preliminary screens, FNAB cytology is done. A (-) FNAB should not dissuade the surgeon from excision biopsy if a discrete lump is present, particularly if there is high clinical suspicion of cancer.
Mammography can be done to localize areas with high probability of cancer aiding direction of FNAB.
Review of slides is done to verify presence of cancer for those patients already with biopsy slides.
(C) Majority of breast cancer are invasive ductal carci-noma. Three major cancer types are: noninvasive (intraductal and lobular), invasive, and Paget's disease of the nipple. Poor prognosis types are atypical medullary and not otherwise specified. Other histopathologic findings that correlate with poor prognosis are low nuclear grade and presence of tubule formation.
For treatment purposes, breast cancer may be di-
vided into:a. Pure non-invasive carcinoma (Stage 0) i. ductal carcinoma (Stage 0) ii. lobular carcinoma in situ (LCIS)b. Operable locoregional invasive carcinoma
(Stage I, II and some stage IIIA)c. Inoperable locoregional invasive carcinoma
(Stage IIIB, IIIC and some stage IIIA tu-mors)
d. Metastatic or recurrent carcinoma (Stage IV)
(D) Staging considerations:
History and PE, and at a minimum alkaline phospha-
tase, chest x-ray, abdominal ultrasound are done for baseline. Bone scan is indicated if the patient has symptoms related to bone or if there is elevated alka-line phosphatase level. CT scan of whole abdomen is indicated if abdominal ultrasound is inconclusive but there ae symptoms referable to the abdominal organs.
At a minimum baseline CBC, creatinine, and ECG are done in preparation for treatment.
PET scan can be an option to determine presence of metastatic sites highly suspected but not shown by CT scan/bone scan. For brain metastasis suspect, MRI may be the better option compared to CT scan.
(E) The goal of treatment of in-situ carcinoma is either preventing the occurrence of invasive disease or diagnosing the invasive component when still local-ized to the breast.
Observation alone is the preferred option for women
diagnosed with LCIS because their risk of deve-loping invasive carcinoma is low. Bilateral mastec-tomy may be considered in special circumstances.
Tamoxifen treatment may be considered in women with DCIS treated with breast conserving therapy, especially in those with ER(+) DCIS treated with mastectomy.
(F) Fresh surgical breast mass specimen must be rou-tinely taken at FIRST surgery for ER/PR assay and level of HER-2/neu expression, needed to plan drug treatment of patient. For stage IV or for those cases not previously performed, it is best to deter-mine even on just the excision biopsy specimen the ER/PR and HER-2 status.
Hormonal therapy has been shown to reduce overall tumor recurrence and mortality in ER(+) women. Tamoxifen or an aromatase inhibitor agent is the usual hormonotherapy drug. The best responder would be an ER(+)/PR(+) patient; for those pre-menopausal, tamoxifen can be given; for those post-menopausal, tamoxifen or aromatase inhibitor can be given. For those ER(+)/PR(-), the PR(-) status may be a marker for growth factor overexpression (Her-2 overexpression) and this subgroup of post-menopausal patients may be best started on aroma-tase inhibitors.
HER-2-neu overexpression denotes an aggressive
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cancer, resistance to CMF but responsiveness to anti-Her-2-neu immunotherapy (trastuzumab). A combination of HER-2-neu ≥++/PR(-) con-notes resistance to CMF-based regimen and tamoxifen.
(G) The purpose of surgery is to remove the local and regional disease. A number of randomized trials document that in the majority of women with Stage I and II invasive breast CA, mastectomy with axil-lary dissection versus breast conserving therapy with lumpectomy, axillary dissection and breast irradiation (breast conserving therapy) are medically equivalent primary therapeutic options. MRM still remains the better option for clinical settings with low patient follow-up rates or low resource set-tings.
Surgical management is the responsibility of the surgical oncologist.
(H) For high risk patients with ≥4 (+)LN and (-)ER or for those premenopausal and (-)LN or with HER-2-neu over expression, anthracycline-containing adjuvant chemotherapy is given. Otherwise, CMF can be given, particularly for elderly and or patients with heart disease; taxanes can also be given particularly for young, ALN(+) 0-3, aggressive and ER/PR(-) tumors.
(I) If adjuvant chemotherapy is indicated, RT should be given after chemotherapy is completed. Radio-therapy is the responsibility of the radiation onco-logist.
It was hoped that post-op RT could prevent loco-regional recurrence and improve disease-free and overall survival. It is now evident, however, that this has not occurred to the degree hoped for, prob-ably because remaining tumor burden is too great. Hence, adjuvant systemic chemotherapy is given.
More common chemotherapeutic drugs used cur-rently in breast cancer management (neoadjuvant, adjuvant, or palliative setting) are doxorubicin and the other anthracyclines, cyclophosphamide, fluorouracil, taxanes, navelbine, capecitabine, gemcitabine, methotrexate, vincristine, mitomycin-c, carboplatin, trastuzumab.
Drug management (from hormonotherapy to gene therapy in the adjuvant to palliative setting) is the responsibility of the medical oncologist who does the planning, the administration, and the monitoring of drug therapeutic and safety effects.
(J) Preoperative chemotherapy for large clinical Stage
IIA and IIB tumors and T3N1M0 tumors should be considered for women who meet the criteria for breast conserving therapy except for size.
(K) Metastatic sites for breast cancer are usually the regional LNs, skin, lung, liver, bone, brain, etc. Stage IV breast cancer can be those with:
1. 'operable-like' breast mass but with distant meta-stasis wherein simple mastectomy followed by radiotherapy of target breast and regional LNs sites and symptomatic metastatic sites plus chemotherapy/hormonotherapy, OR wherein radiotherapy to target breast lesion/other symp-tomatic metastatic sites plus chemotherapy/hor-monotherapy can be done,
2. 'inoperable-like' breast mass (adhered, ulcer-ated, etc) with distant metastasis, wherein toilette mastectomy can be done with chemo-therapy/hormonotherapy or radiotherapy or best supportive care.
Surgery, chemotherapy, radiotherapy procedures in Stage IV disease are all palliative in goal, although sev-eral patients can respond very well to chemotherapy ± radiotherapy and have significantly long time to disease progression interval. Best supportive care mainly in-cludes management of nutrition, pain, infection, psycho-logical well-being, nursing and rehabilitative care, and other pertinent quality of life patient care.
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Drugs Mentioned in the Treatment GuidelineThis index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing information of these drugs can be found in the PPD reference systems.
cytotoxicDrugsAlkylatingAgentsCyclophosphamide
CytoxanMelphalan
AlkeranAntimetabolites5-Fluorouracil
Biomedis FluorouracilFluracedylFluroblastinUflahex
CapecitabineXeloda
MethotrexateBiomedis MethotrexateEmthexateHextratePfizer Methotrexate Inj.
Tegafur/UracilUFT
cytotoxicAntibioticsDoxorubicin HCl
Adriblastina RDBiomedis Doxorubicin HClCaelyxPfizer Doxorubicin HCl InjPharmachemie Doxorubicin
Epirubicin HClPharmorubicin
Mitomycin CKyowa Mitomycin-C
mitoticInhibitorsDocetaxel
TaxotereVincristine sulfate
Biomedis Vincristine SulfateNevexitinPfizer Vincristine InjectionPharmachemie Vincristine
OthercytotoxicsCarboplatin
BiovinateCrobextinParaplatin
Gemcitabine HClGemzar
MitoxantroneDomitrone
paclitaxelTaxol
Hormones andAntagonists inmalignantDiseasesAnastrozole
ArimidexGoserelin acetate
ZoladexLetrozole
FemaraLeuprorelin acetate
LuprolexMegestrol acetate
MegacePharmachemie Megestrol
AcetateTamoxifen citrate
Cox TamoxifenDrugmaker's Biotech TamoxifenFenahexKessarNolvadex/Nolvadex-DTamoplexZitazonium
ImmunosuppressantsExemestane
AromasinOthersTrastuzumab
Herceptin
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Algorithm for the Management of Lung Cancer
No Mass?
Figure1
No other CA site?
CT Scan(C) No mass?
Close follow
up. Refer
Centrally located?
Peripheral location?
Enlarged neck
nodes?
Broncho-scopy with biopsy or
cytology (D)
Manage bycase. Refer
PercutaneousFNAB
(E)
Go to # 9
Go to Fig. 1a
Go to Fig. 1a
Go to Fig. 1a
Pleural effusion?
Biopsy
Thoracentesis with cytology
(F)
Highly suspect cancer?
Radiotherapy
Lung CASuspect
(A)
Chest X-ray
PAL (B)
Go to Fig. 1a
Refer
1
2
3 4 5 6 7
8
910
1112
13 14
1516
17 18
19
Y Y Y
Y
Y
Y
Y
Y
N
N N
N
N
N
N
N
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No cancer?
(G)
Highly suspectcancer?
Figure1a
Radio-therapy
Refer
SCLC? Stage(H)
T1T2N0M0?
Not Operable? Rt and/orChemotherapy
Lobectomy(J)
Adjuvant Rt(K)
and/orChemotherapy
(L)
T3T4N1-3M0?
Metastatic
Palliativechemotherapy
and or Rt
Chemothe-rapy ±
Rt
Go to Figure 1b
Y
N
Y
Y
Y Y
Y
N
N
N
N
N
1 2 3
4
5 6
7 8 9
10 11
1213
14
15
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NSCLC
Stage(I)
1
Figure1b
Stage I?Y
3
2
Stage II/III?
9
Y
N
N
Stage IV
Single sitemets?
Y
N
Multiple
16
18
22
PalliativeTreatment
24
Operable?Y
N
Operable?Y
N
Rt
Rt + Chemo
Surgery Rt
Close follow up
Surgery
Surgery
Chemo ±Rt
Palliativetreatment
Chemo/Rt
Y
19
N
+margins? Y
7
N
Resectable? Y
14
N
Operable?
20
4 5
8
6
10 11 12
13 15
17
23
Chemo ±Rt
21
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The management of lung cancer must be multi-dis-ciplinary and interdisciplinary, with each discipline respecting the specialty expertise of the other, all for the benefit of the cancer patient.
(A) A change in pulmonary habits is the most signifi-cant sign of lung cancer. Coughs, chest pain, rust colored-streaked sputum, hemoptysis, hoarseness, weight loss, and dyspnea are common symptoms of lung cancer.
(B) Posteroanterior and lateral chest films are the most valuable first tolls to establish the diagnosis when there is clinical suspicion of lung cancer.
(C) Asymptomatic smaller tumors can be detected by the CT scan. For lung cancer suspect, do CT scan of chest, upper abdomen and adrenal glands. CT scan is also the most useful of all modalities for determining the characteristics of T and N in the thorax and M in the brain and liver.
(D) Bronchoscopy yields (+) histology only if the lung cancer is centrally located or has invaded centrally. Cytological studies include sputum and bronchial washing exams by Papaniculao technique.
(E) Percutaneous needle biopsy guided by fluoroscopy or CT scan gives accurate cytologic diagnosis from peripheral lung lesions and also from liver/bone metastatic lesions.
(F) Pleural fluid can undergo cytologic exam when pleural effusion is the presenting symptomatol-ogy.
(G) There are 2 major histological types, whose manage-ment differ accordingly: 1) small cell anaplastic carcinoma (SCLC)- tends to be disseminated at diagnosis; rapidly growing, 2) Non-small cell car-cinoma (NSCLC)- slow growing; with three cell types: a) epidermoid carcinoma - most common centrally located, b) adenocarcinoma - tends to be peripherally located, c) large cell anaplastic car-cinoma - similar to adenocarcinoma in metastatic pattern.
For both SCLC and NSCLC, staging work up includes CT scan of chest, upper abdomen and adrenal glands (if not yet done in diagnostic work up), ultrasound of the liver (if upper abdomen CT scan was not done), brain and bone scans (if sympto-matic).
(H) SCLC Stage:1. Limited disease confined to lung and regional
lymph nodes.2. Extensive disease - denotes metastasis outside
lung and regional lymph nodes.
(I) NSCLC stage by TNM classification
A.TNma. Tis carcinoma in situb. T1<3 cm tumor size not involving the visceral
pleurac. T2>3 cm tumor size, >2cm from the carina, (+)
viscerali. pleural involvement, partial atelectasis
d. T3 tumor involves the chest wall, diaphragm, mediastinumi. pleura or parietal pericardium, <2 cm
from the carina, complete atelectasis of either lung
e. T4 tumor involves the mediastinum, heart, tra-chea, i. carina, vertebral body; presence of malig-
nant pleural/pericardial effusion; presence of satellite nodule/tumor
f. N0 No spread to lymph nodes (LN)g. N1 Spread to LN within the lungs, ipsilateral
hilar LNsh. N2 Spread to subcarinal or ipsilateral mediastinal
LNsi. N3 Spread to cervical LNs or contralateral hilar
andi. mediastinal LNs
j. m0 No distant spreadk. m1 Spread to distant organs, to other lobes of
thei. lungs or to LNs further than those mentioned
in N stage
b. sTAGea. 0 - TisN0M0b. IA - T1N0M0c. IB - T2N0M0d. IIA - T1N1M0e. IIB - T2N1M0,T3N0M0f. IIIA - T1-T3N2M0,T3N1M0g. IIIB - AnyTN3M0, T4AnyNM0h. IVB - AnyT AnyN M1
(J) In SCLC T1-2N0M0 and NSCLC Stage I and II, sur-gery is done to achieve complete tumor resection and avoid an exploratory thoracotomy or an incomplete surgical resection. The choice of surgical procedure - lobectomy, pneumonectomy, segmental or sleeve
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resection - depends on disease extent and patient's functional status. Here, surgery may not be done if with medical contraindications. The presence of distant metastases or extrahepatic metastasis is indicative of inoperability and a surgical procedure is an absolute contraindication.
Surgical management is the responsibility of the surgical oncologist and or the thoracic surgeon.
(K) Irradiation is used to achieve:1. Definitive irradiation of localized lung cancer2. As part of a combined treatment approach3. Palliation of symptoms
Radiotherapy can be given in combination with chemotherapy if a patient is assessed (age, ECOG performance status, co-morbidities, preference) to be able to receive combination modality of treat-ment.
Radiotherapy is the responsibility of the Radiation Oncologist.
(L) In SCLC, combination chemotherapy is the treat-ment of choice for all stages. In SCLC, chemother-apy is currently restricted to recurrent or metastatic disease and for palliation of inoperable symptomatic patients whose disease is beyond radiotherapy con-trol. Recent data also suggested benefits for Stage III disease after surgery or radiotherapy. Neoadjuvant chemotherapy is reported to be promising due to better staging procedures and use of cisplatin-con-taining regimens.
Drug therapy for cancer is the responsibility of the Medical Oncologist.
Initial work up prior to any treatment include base-line CBC, creatinine, serum electrolytes, LDH.
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Drugs Mentioned in the Treatment GuidelineThis index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing information of these drugs can be found in PPD reference systems.
cytotoxicDrugsAntimetabolitesMethotrexate Biomedis Methotrexate HextrateTegafur/Uracil UFTcytotoxicAntibioticsDoxorubicin HCl Adriblastina RD Biomedis Doxorubicin HCl Pfizer Doxorubicin HCl Inj Pharmachemie DoxorubicinmitoticInhibitorsDocetaxel TaxotereEtoposide Lastet Pfizer Etoposide Posid Topresid VepesidVincristine sulfate Biomedis Vincristine Sulfate Nevexitin Pfizer Vincristine Inj Pharmachemie VincristineOthercytotoxicsCarboplatin Crobextin ParaplatinCisplatin Ciplexal Nippon Kayaku Cisplatin PlatamineGemcitabine HCl GemzarPaclitaxel TaxolOthersGeftinib Iressa
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