Clinical Oncology SC018: Oncology In Practice: Multidisciplinary Management Of Common Cancers Flashcards
Oncology
Prevention, Diagnosis, Treatment of cancer
Divisions:
- Surgical oncology
- Radiation oncology
- Medical oncology
- Clinical oncology (Medical + Radiation: mainly solid tumours)
Site specific subspecialty:
- e.g. Haematologic oncology, Thoracic oncology, Gynaecologic oncology
Subspecialty for paediatrics: Paediatric oncology (mostly medical oncology)
Presenting S/S of cancers
Related to:
- Tumour growth
- Tumour invasion / infiltration —> Disruption of normal tissue / organ function
S/S:
- Lumps and bumps
- breast lump
- LN enlargement - Bleeding (∵ abnormal blood vessels)
- GI / genitourinary bleeding - Pressure effect
- GI obstruction
- respiratory tract obstruction
- ↑ ICP - Pain
- tumour do NOT have normal nerve endings —> often **painless
- pressure effect / sign of local invasion to pain sensitive surrounding structures e.g. bone, nerves
- often a **late symptom - Disruption of normal organ functions
- neurological deficit
- pathological fracture
- SOB - Metabolic / Hormonal symptoms
- paraneoplastic syndrome
- hormonally active tumour
Example: S/S of NPC
Depends on extent of disease:
Anterior:
- Nasal obstruction
- Nasal tone in speech
- Epistaxis
Superior:
- Headache
- CN palsies
Inferior:
- Sore throat
- Oropharyngeal mass
Lateral:
- Ear obstruction
- Decreased hearing
- Trismus
Posterior:
1. Neck pain
Neck:
1. LN enlargement
Distant metastasis:
- Bone pain
- Chest symptoms
P/E:
- Local
- Regional
- Systemic
- Neurological
Diagnosis + Staging
Depends on site + type of cancers
Diagnosis:
- usually based on **Histology (esp. Molecular diagnosis)
—> risk and yield of histological diagnosis should be considered
- somtimes **Clinical, **Clinical-radiological, **Clinical-biochemical (hCG in germ cell tumour in male)
Purpose of Histology:
- ***Confirmed malignancy
- Different histological types carries different ***prognosis / response to treatment
- ***Molecular markers can be performed on biopsies (e.g. ER, PR, HER2, Ki-67 status in breast cancers)
- Biopsy from metastatic sites may suggest the ***primary location by morphology + IHC
Tumour markers:
- AFP
- Beta-hCG
- CEA
- CA125
- PSA
Staging:
- Clinical
- Radiological
- Endoscopic
Diagnosis
Diagnosis:
- usually based on **Histology (esp. Molecular diagnosis)
—> risk and yield of histological diagnosis should be considered
- somtimes **Clinical, **Clinical-radiological, **Clinical-biochemical (hCG in germ cell tumour in male)
Mostly involve biopsy:
- Endoscopic
- Image guided
- Cytology (e.g. FNAC)
- Surgical (Incisional / Excisional)
Histological diagnosis:
- ***Architectural information (in addition to Cellular morphology i.e. Cytology) (e.g. lymphoma, sarcoma, follicular carcinoma of thyroid —> tissue biopsy required)
- Some molecular studies may require fresh tissue
- Clinical-radiological correlation is required (e.g. sarcoma)
Histological grading:
- Degree of ***differentiation of tumour cells (compared to normal tissue)
- Less differentiated tumour are more aggressive + rapidly proliferating
- Different grading systems for different cancers
Recurrent disease:
- Biopsy to confirm:
1. Recurrence
2. Second primary
3. Monitor change in molecular markers (molecular signature may change from initial presentation)
4. Repeat biopsy may be required to guide treatment
Liquid biopsy:
- Take blood
- Monitor dynamic change in tumour characteristics e.g. tumour DNA / circulating tumour cells
Staging
Classification of prognostic groups:
- Benchmarks for comparison of treatment outcomes in clinical trials, different centres
AJCC / UICC system: - ***TNM staging - revised every 6-8 years (based on level of evidence of new diagnostic information, change in treatment efficacy, expert consensus) - classify extent of disease based mostly on anatomic information on —> ***Extent of primary tumour —> ***Regional LN —> ***Distant metastases —> combined overall stage
***Stage migration:
- advances in technology in diagnosis
—> T / N staging change from P/E to CT/MRI
—> M staging change from CXR / Bone X-ray to CT / Bone scan / PET
—> Able to detect smaller, deeper lesions
Tumours with same stage from different eras may not be directly comparable:
- confounding factors:
1. Change in diagnostic
2. Therapeutic strategies
—> Historical control is less reliable than ***Contemporary control than Randomised control
Staging vs Grading
- Stage: ***Extent of disease
- Grading: ***Biology of cancer
Some staging classification includes grading, e.g. sarcoma
Anatomical staging, may be augmented by including **biological prognostic and **predictive markers to form prognostic groups (e.g. mitotic rate in staging of GIST, PSA and Gleason score in overall staging of CA prostate)
AJCC 8th edition:
- Oropharyngeal carcinoma has different staging system for HPV (p16) +ve or –ve disease (first time ever molecular diagnosis incoporated into staging)
AJCC stage:
- meant for ***newly diagnosed cases
- Recurrent disease is inherently of worse prognosis even if the anatomical extent of disease is similar to a newly diagnosed one
Anatomical staging is based on information from:
- Clinical examination
- Radiological examination
- Surgical findings
- Pathology findings
Clinical-radiological staging:
- no prefix, e.g. T1N0M0 stage IA CA breast
Pathologic staging:
- prefix: ***pT1N0M0, stage IA CA breast
Clinical-radiological or pathology staging after ***neoadjuvant treatment:
- Pre-treatment clinical-radiological stage: cTNM
- Post-neoadjuvant therapy stage:
—> ycTNM if based on clinical-radiological stage
—> ypTNM if based on pathologic findings
Multidisciplinary management
A multidisciplinary approach:
- drawing appropriately from multiple disciplines to redefine problems outside normal boundaries
- reach solutions based on a new understanding of complex situations
Multi-disciplinary tumour boards: - clinical meetings in which cancer cases are discussed and the best management plan formulated - disciplines include —> medical oncologist —> surgical oncologist —> radiation oncologist —> pathologist —> radiologist —> organ specific oncologists —> nurses and other paramedical staff —> scientists (***Precision medicine leads to ***molecular tumor board)
Aim: to find the best possible management for an individual patient considering the physical, social, psychological, emotional and financial status of the patients
Multidisciplinary vs Interdisciplinary vs Transdisciplinary
Interdisciplinarity:
- involves the combining of >=2 academic disciplines into one activity (e.g. a research project)
- creating something new by crossing boundaries, and thinking across them
- related to an interdiscipline or an interdisciplinary field, which is an organizational unit that crosses traditional boundaries between academic disciplines or schools of thought, as new needs and professions emerge
Transdisciplinarity:
- connotes a research strategy that crosses ***many disciplinary boundaries to create a holistic approach
- applies to research efforts focused on problems that cross the boundaries of two or more disciplines, such as research on effective information systems for biomedical research (bioinformatics)
The 3 terms refer to the involvement of multiple disciplines to varying degrees on the same continunum. The common words for multidisciplinary, interdisciplinary and transdisciplinary are additive, interactive and holistic respectively
- Can be applied in ***health research, services, education and policy
- Application of ***AI, big data in medicine
Treatment
Depends on **Site + **Type of cancer:
5 pillars:
Local-regional:
- Surgery
- RT
Systemic:
- Chemotherapy (Hormonal therapy)
- Target therapy
- Immunotherapy
Early stage disease:
- usually can be cured with ***single modality e.g. surgery / RT alone
Advanced stage disease:
- require ***multimodality treatment —> require multidisciplinary treatment
Multimodality treatment
Combines different modalities in treatment of a single disease
Advantages:
- ***Spacial augmentation (systemic augmented to local treatment) (e.g. treatment of occult metastases, sanctuary sites by systemic treatment)
- ***Downstaging of disease before definitive treatment
- ***Organ preservation
- ***Reduce toxicity of individual modality
Local-regional treatment: 1. Surgery - limited by anatomy - removal of tissue —> ***Loss of organ function —> Need ***reconstruction —> ***Rehabilitation
- RT
- limited by anatomy
- useful for surgical inaccessible / unresectable / inoperable tumours (e.g. Nasopharynx)
- RT / ChemoRT may:
—> **Preserve organ
—> **Improve function, body image
—> ***Better QoL in survivors
Systemic (Medical treatment):
- applicable if **disseminated disease
- limitation:
—> Depends on **sensitivity of tumour cells to individual drug
—> Drug **bioavailability (e.g. cannot cross BBB / BTB (blood-testicular barrier))
—> Precision medicine: Find **druggable target for treatment
Cell kill hypothesis
A given dose of chemotherapy only kills a certain **proportion of tumour cells rather than a fixed no. of cells
—> Drops in a proportion of tumour cells
—> Rebound growth of tumour cells in-between cycles
—> Single modality ineffective if initial tumour burden is large (if only give chemo then will need large no. of cycles)
—> Reason for multimodality treatment (e.g. surgery: kills a **fixed no. of cells)
RT:
- Log-cell kill (kills only a ***proportion of tumour cells)
—> require multiple cycles
***Goal of treatment
- Primary
- **first definitive treatment after diagnosis
- definitive treatment for loco-regional disease
—> aiming at achieving **complete remission, best chance of cure
—> Surgery, ChemoRT, Radical RT - Radical
- aims to **eradicate cancer, achieving complete remission, **long term cure
- ***more toxicity from treatment may be acceptable in order to achieve better chance of survival - Palliative
- **palliation of symptoms / **prolonging survival / **improve QoL
- not expecting complete remission after treatment
- need to **balance benefit and SE of treatment - Salvage
- treatment that is given after the cancer has **not responded to other treatments (e.g. salvage surgery for local recurrence after chemoRT)
- implies still a chance of achieving **complete remission —> ∴ treatment still ***radical - Complete remission / response
- disappearance of ***all signs of cancer in response to treatment
- NOT always mean cancer cured
- response can be assessed in different ways:
—> Clinical
—> Radiological
—> Metabolic
—> Pathologic
—> Biochemical (e.g. Tumour markers)
—> Molecular (e.g. CML: check BCR-ABL1)
***Sequencing of treatment
- Induction / Neoadjuvant
- Treatment **before **definitive loco-regional treatment (e.g. before surgery / RT)
- Aim:
—> **Downstaging of disease —> Organ preservation
—> **Test out response to treatment
—> Improve survival by ***early initiation of systemic treatment for disease at high risk of occult systemic dissemination - Adjuvant
- Treatment **after definitive loco-regional treatment when there is **NO gross evidence of residual disease
- Aim:
—> Improve chance of loco–regional control
—> ***Eradicate occult systemic disease - Concomitant / Concurrent
- usually refer to RT used in definitive treatment
- >=2 modalities used at the same time
—> ChemoRT
—> Bioradiation (Biological agents (e.g. mAb) + RT) - Sequential
- 1 modality / regime after another
- e.g. induction chemo —> then RT / chemoRT
- concurrent chemoRT —> then adjuvant chemo - Alternative (less commonly used)
- Chemo given ***in between slots of RT
Neoadjuvant treatment
Examples:
- Neoadjuvant chemotherapy / hormonal therapy / target therapy before surgery for breast cancers
- allows for better chance of breast conserving surgery (**downstaging and **organ preservation)
- test for ***sensitivity to target / hormonal treatment - Neoadjuvant chemoradiation (concurrent) for rectal cancer and esophageal cancer
- **downstaging
- **sterilize the surgical field
- better local control
- improve chance of ***sphincter preservation - Pathological CR (complete remission) usually implies ***good response to treatment and better
outcomes - Response to neoadjuvant treatment may be used to ***tailor subsequent treatment
- e.g. CA larynx: good responder to neoadjuvant chemotherapy —> can go on to radical chemoRT with preservation of larynx while poor responder will have surgery (laryngectomy)
- Osteosarcoma: good responder to pre-op chemotherapy will continue with same drugs / combination after surgery but poor response is an indication for use of different post-op chemotherapy
Disadvantage:
- Cannot ***predict response to treatment
- May ***delay the primary definitive treatment in non-responder
- Some responding patient may refuse subsequent definitive treatment
- Surgery more difficult and wound healing may be impaired with pre-op RT
