Cancer Therapies Flashcards
The factors that affect the choice of therapy include:
- Site
- Spread
- Stage
- Histology
- Patients general condition
- Sensitivity of tumour
- Patient preference
- Resources
Treatment modalities
Surgery
Radiotherapy
Drug therapy
- Chemotherapy
- Targeted therapy
- Immunotherapy
- Endocrine therapy
Best supportive care – symptom control
Treatment approaches
- Radical/palliative (radical aims to get rid of cancer completely, palliative are used to slow the growth of cancer and relieve the symptoms)
- Sole treatment modality
- Part of a combined therapy
- Adjuvant therapy (given in addition to the primary treatment afterwards)
- Neo-adjuvant (given before primary
treatment) e.g shrink tumour before surgery - Prophylactic therapy (preventative) - endocrine therapy, maybe remove ovaries and fallopian tube after kids if susceptible to cancer
Cancer Staging
Description of how far the cancer has spread
Determined by imaging +/- surgery/biopsy
Determines best modality of treatment and whether curative/palliative intent
Surgery can be used as a treatment for cancer patients and can be used in a number of ways:
For management of the primary tumour, for management of regional lymph nodes and/or the use of palliative surgery.
Surgery primary tumour management may be used in several ways including: To do a tissue biopsy to establish a diagnosis. To remove a malignant disease that has a clear margin with normal tissue, as well as for repair, reconstruction and restoration of normal function.
Surgical excision of regional lymph nodes (lymph nodes around the area where the cancer is), is commonly done in order to see if the cancer has spread. If an individual has breast cancer, the axillary nodes will be looked at, if head/neck cancer then a radical neck dissection will be done and if cancer of vulva, anal and or penile tissue then an inguinal node dissection will be done.
Palliative surgery is used for a number of things, but its overall purpose is to control the disorder. So for example, relief of obstructive symptoms, control of haemorrhage, tumour fungation and fracture fixation.
Radiotherapy
Radiotherapy is the treatment of malignant disease with high energy x-rays or gamma rays. Radical and palliative approaches can be used, on a wide range of tumour sites.
An external beam can be used, such as particle therapy, or internal radiotherapy (also known as brachytherapy), where a radioactive source is placed inside the patient and very high doses given over a short period of time.
Radiotherapy
external beam
A linear accelerator is used to give dosages of radiation. They fire high energy electrons. It can do 360 degree movement around the patient, and has the laser system as well as an imaging system.
CT plan
define treatment area
identify organs at risk
dose calculation
Side effects of radiotherapy are site dependent, dose dependent and depend on whether the tissue is early or late responding.
Side effects include:
Skin reactions, hair loss, GI disturbances, Tissue fibrosis
Linac set up
Immobilisation & Reproducibility
tattoos
lasers
masks
Chemotherapy
Mechanisms of action
Mechanisms of action: -> DNA damage - leads to double stranded DNA breaks -> inhibit mitosis -> inhibit DNA replication which will lead to APOPTOSIS
Most effective against fast growing cancers
How chemo affects different cancers?
High sensitivity
- leukaemia, lymphoma, germ cell tumours, small cell lung cancer
Moderate sensitivity
- breast , colorectal, bladder, ovary, cervix
Low sensitivity
- prostate, kidney, primary brain tumours, melanoma
- respond better to targeted treatments
Cancers which are clonal – ie. cells are all the same – respond better to chemo
Cancer with lots of mutations are more likely to be resistant or become resistant to treatment
Generic side effects
Generic
- damage to rapidly dividing normal cells
- fatigue (anaemia + low platelets and wbc means higher chance of infection)
- myelosuppression + risk of infection
- skin toxicity – rash, alopecia
- GI disturbance – nausea, change in taste, - vomiting, diarrhoea/constipation, mucositis
- venous thromboembolism – DVT/PE (blood is more viscous)
Drug-specific side effects
Drug-specific:
- peripheral neuropathy + tinnitus (Cisplatin, Paclitaxel)
- nephrotoxicity (Cisplatin)
- pneumonitis + pulmonary fibrosis (Bleomycin)
Late Side effects
Cardiotoxicity
- cardiomyopathy
- atherosclerosis and IHD
Secondary malignancies - leukaemias
Targeted therapy
Biopsy will tell you subtype of tumour type or specific mutation in cancer
- Small molecule/enzyme inhibitors (end in nib)
eg. Sunitinib in clear cell renal cancer
Erlotinib in EGFR mutated lung cancer
Dabrafenib in BRAF mutated melanoma - Monoclonal antibodies (end in mab) (iv)
eg. anti-HER2 Trastuzumab (Herceptin) in breast Ca
anti-VEGF Bevacizumab in ovarian Ca
IF NO GENE ALTERATION START CHEMO
Endocrine therapy
Used in hormone driven cancers
Breast – Tamoxifen, Anastrazole
Prostate – Zoladex, Enzalutamide
Long term adjuvant therapy
Prophylactic
Tamoxifen - Binds to Oestrogen receptors, reducing the synthesis of growth factors & stimulating the production of progesterone receptors. As a result, cell division is arrested at G1 phase of the cycle. Only used if breast cancer is ER positive
Zoladex blocks hormonal signals from the brain that initiate testosterone production. This action prevents cells growing & causes cell death. Zoladex is given before EBRT to shrink the tumour size. 3 monthly injections, used until disease becomes resistant to medical castration
Immunotherapy - how it works
Immune system evasion is a Hallmark of cancer (therefore lymphocutes don’t recognise its not normal)
Immunotherapy switches immune system back on -> Monoclonal antibodies to block pathways that cancer has upregulated to evade the immune system so the cytoxic resposne won’t be prevented
Immunotherapy - works best for?
Works better in cancers with lots of mutations and neo-antigens
SEs: inflammatory & auto-immune conditions
eg. rash, colitis, thyroid dysfunction, pneumonitis
Melanoma is a good target and liver and lung
Immunotherapy - types
Cancer vaccines - new antigens on cancer cells so stimulate immune response
Modulated T cell therapies
- train your own immune system to recognise and fight your cancer for you
- > TILs
- > CAR-T cells
TILs and CAR-T cells
TILs (tumour infiltrating lymphocytes) are collected from the tumor during a biopsy, or surgical resection, and grown to very large numbers in a laboratory with interleukin-2 (IL-2), a protein that promotes rapid TIL growth. Once successfully grown to billions in number, the TILs are infused back into the patient, where they actively attack cancer cells while leaving healthy cells alone
CAR-T cells (chimeric antigen receptor): Apheresis to collect T cells which are changed in the lab - designed to recognise and target a specific protein on the cancer cells
Both given back with cytokines to stimulate immune system – can cause cytokine release syndrome where pt very unwell.
Which therapy and why?
Site Spread Stage Histology + mutation status Patients general condition – performance status, co-morbidities Sensitivity of tumour Patient preference (consent) Resources (nhs resources limited)
Case 1a
64 year old male
Stage IIa bronchogenic carcinoma
Non small cell lung cancer
If operable – surgery with lobectomy/pneumonectomy followed by adjuvant chemo
Otherwise radical chemo-radiation (eg. if co-morbidities precluding surgery)
Case 1b
64 year old male
Stage IV bronchogenic carcinoma
Non small cell lung cancer
Biopsy – EGFR or ALK mutation?
If actionable mutation – give targeted treatment – Erlotinib or Crizotinib
Fit for chemo?
If single metastasis and pt fit – could have palliative surgery to remove brain met
Case 2
73 year old female
Stage IIIC high grade serous ovarian carcinoma
Performance status?
BRCA mutation?
(germline testing on blood)
73 is not necessarily too old for chemo!
All patients given PARP inhibitors now as shown to benefit all, not just gBRCAm pts
Case 3
41 year old female
Stage IV malignant melanoma
Biopsy – BRAF mutation?
If BRAF mutant then could have targeted therapy
Patients all have doublet therapy with Ipilimumab and Nivolumab 1st line now, even if have BRAF mutation - ?pt fit for treatment
Immunotherapy can have outstanding and durable results in some cases
Summary
Mainstays of cancer treatment are surgery, radiotherapy and drug therapy
Treatment chosen depends on:
- histology
- stage of cancer
- performance status of patient
WHat is palliative care?
Palliative care is the active total care of patients whose disease is not responsive to curative treatment.
Control of pain, of other symptoms, and of psychological, social and spiritual problems, is paramount.
The goal of palliative care is achievement of the best quality of life for patients and their families
