The rational treatment of cancer Sergiusz Nawrocki Decision to proceed with treatment • indolent tumors that will not kill the patient • highly aggres...
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The rational treatment of cancer Sergiusz Nawrocki
Decision to proceed with treatment •
indolent tumors that will not kill the patient
•
highly aggresive tumors disseminated by the time of diagnosis
•
tumors of intermediate grade progressing from locally invasive to metastatic disease
Decision to proceed with treatment •
indolent tumors that will not kill the patient
•
highly aggresive tumors disseminated by the time of diagnosis
•
tumors of intermediate grade progressing from locally invasive to metastatic disease
•
incidentalomas: pancreatic NETs, prostate cancers, papillary thyroid carcinomas
•
post mortem studies shows high prevalence, eg prostate ca in 80% after 80 y; thyroid in one-third of autopsies while only 0,07% are causing deaths
•
at age of 80% at least of two-thirds of women carry breast carcinoma
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only 4% will die from breast cancer
Decision to proceed with treatment •
indolent tumors that will not kill the patient
•
highly aggresive tumors disseminated by the time of diagnosis
•
tumors of intermediate grade progressing from locally invasive to metastatic disease
Decision to proceed with treatment •
indolent tumors that will not kill the patient
•
highly aggresive tumors disseminated by the time of diagnosis
•
tumors of intermediate grade progressing from locally invasive to metastatic disease
Risk of second cancers - DNA modifying agents
cyclophosphamide used in early 1980s in BC - 5,7 greater risk of AML
•
2012 in US:
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227 000 new breast cancers, 63 000 DCIS, 40 000 deaths
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possibly 3/4 will not cause death even without intervention
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90% new invasive BC patients will receive adjuvant chemotherapy
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chemotherapy improves survival by 6% (from 75% to 81%)
Surgery assumptions •
small tumors will grow into large ones and incurable
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resecting primary tumor reduces risk of metastases (resection of T1 colon adnoca yields 95% cures without adjuvant treatment)
Mastectomy modo Halsted
Late vs early dissemination models
chemotherapy assumptions
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adjuvant chemotherapy kills micrometastases
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adjuvant chemotherapy improves survival rates
Adjuvant therapy for breast cancer is any treatment given after primary therapy to increase the chance of long-term survival. Neoadjuvant therapy is treatment given before primary therapy • Adjuvant therapy for breast cancer can include chemotherapy, hormonal therapy, the targeted drug trastuzumab (Herceptin®), radiation therapy, or a combination of treatments. • Patients who have a higher risk of breast cancer recurrence are more likely to need adjuvant therapy. Doctors look at both prognostic and predictive factors to decide which patients might benefit from adjuvant treatments.
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EBCCG metaanalysis, Lancet, 2005
EBCCG metaanalysis, Lancet, 2005
ER (+) or unknown
Ovarian supression or ablation in ER (+) or unknown
Circulating Tumor Cells
Multi-drug pumps
Molecular diagnostics and targeted therapies have changed the prospects for pts with common cancers with bad prognosis
a case of lung adenocarcioma with mutated EGFR
not only tumor genotype but also patient’s genotype matters…
Why targeted therapies fail?
Tumor stem cells
