RENI Flashcards
(21 cards)
What do we need to give appropriate diagnosis?
Proximate health history, physical exam, family history, lifestyle, eating habits, occupational field, blood and imaging tests.
Useful tools include : US,CT, MRI, PET scan, endoscopy, tumor marks, organ specific examinations.
Difference between recurrence and regression?
- Recurrence means the cancer has come back after surgery/chemotherapy, so the tumor was removed completely and has reappeared.
- Progression means the cancer is growing or spreading without ever having gone away completely.
Staging and grading?
Staging is the classification of the severity of a disease based on established criteria. The most important system is the TNM system which stands for Tumor, Nodes and Metastasis. It used for classifying solid tumors.
T describes the size of the tumor and how far it has spread into the nearly tissue T1 to T4.
N describes whether the cancer has spread to the regional lymph nodes. N0 to N3.
M describes whether the cancer has spread to another part of the body.
Based on the previous information we can than stage tumors from I to IV.
Cancer grading is the description of the grooms appearance of the tumor. Grade I (most differentiated) to grade III (least differentiated).
What do symbols R, L and V mean?
R stands for resection margin.
L for lymphatic invasion.
V for venous invasion.
What is response assessment in Response Evaluation Criteria In Solid Tumors?
The Response Evaluation Criteria in Solid Tumors (RECIST) is a standardized set of guidelines used to assess how solid tumors respond to treatment, particularly in clinical trials. It provides objective criteria to determine whether tumors have decreased, remained stable, or increased in size, thereby evaluating the effectiveness of anticancer therapies.
Evaluation of tumor response to therapy and incorporation of the results in the practice of clinical oncology provide the basis for advances in cancer treatment.
The main purpose is to define respectability and determine surgical approach. We have different types of response : complete response, partial response (30% of reduction in tumor size), stable disease (no response or progression) and progressive disease.
Measurable vs non measurable lesion in Response Evaluation Criteria In Solid Tumors?
Measurable lesion: accurately measure in at least one dimension with a minimum size of :
- 10 mm by CT scan.
- 10 mm caliper measurement by clinical exam.
- 20 mm by chest X-ray.
- If you consider a lymph node it must be > then 15mm in the short axis
Non measurable lesion : we cannot measure a reliable size of the tumor. This include leptomeningeal disease, inflammatory breast cancer disease. Common sites include bone, cystic lesions and lesions with previous local therapy.
How to assess response in RECIST?
All baseline evaluation should be performed as close as possible to treatment start and never more than 4 weeks before the beginning of the treatment. The same methods of assessment and the same technique should be used to follow up.
CT is the best, followed by MRI.
US and tumor markers are not the best to assess tumor response.
Assessment of overall tumor burden in RECIST?
We measure target lesions with a maximum of 5 total lesion, max 2 lesions per organ, representative of all involved organs and leads to reproducible repeated measurements. A sum of the diameters for all target lesions will be calculates as the baseline sum diameters.
Based on that :
Complete response : disappearance of target lesions and each node decreasing by 10mm on short axis.
partial response : 30% decrease of the sum of diameters of target lesions.
Progressive disease : 20% increase of sum of diameters.
stable disease : no sufficient decrease or increase of diameter.
What is pseudoprogression? When does it occur?
It is an increase in size or a new lesion when using immunotherapy. As response patterns are different from chemotherapy. The progression in term of size may be a result of immune cell infiltration in the tumor. So, the increase of the size visible in CT scan is not the increase of the number of tumor cells but in size cause of the immune infiltration- something like a pseudoprogression.
Pseudoprogression is generally not very common, but occurs in 4-10% of cases in melanoma and 1-5% in NSCLC.
For this reason we have the iRECIST applicable to immunotherapy.
What is hyperprogression?
Hyper progression is a severe progression of tumor burden and in tumor growth rate after treatment initiation by a factor of 2.
- Occurs in up to 9% of patient with different histological tumor types.
- Associated with worse overall survival.
What is response assessment in neuro oncology?
RANO is a set of criteria developed specifically for assessing response and progression in brain tumors, such as gliomas and other CNS neoplasms. Unlike standard RECIST, RANO takes into account the unique challenges of neuro-oncology, especially when using MRI for tumor monitoring.
We can use RECIST for brain tumors because contrast enhancement is misleading, as T1 weighted sequences often show BBB disruption and not necessarily tumor growth.
What is a clinical trial? What is the purpose?
A CT is a type of research that studies, by using scientific criteria, new tests and medical, surgical or behavioral interventions and evaluates their effects on human health outcomes
- The purpose is to give an answer to proper and well-defined questions that are relevant for clinical practice, by means of clinical data achieved with correct methodology
- CTs provide a scientific basis for advising and treating patients, so the question must be “who have to treat with this treatment?”, “ where I have to treat the patients?” “ what is the purpose?” and so one…
Clinical trial glossary?
OVERALL SURVIVAL : time from randomization to death from any cause. Survival is calculated from the first diagnosis, not from the start of the target therapy. In some cases, the initial diagnosis anticipated the molecular profiling and the start of target agents by 4/5 years-
-DISEASE-FREE SURVIVAL time from randomization until recurrence or death from any cause. Typically used in adjuvant trials.
This means that the patients had the complete disappearance of the tumor after resection, chemotherapy or radiation. So complete remission, tumor is no longer visible
- PROGRESSION-FREE SURVIVAL time from randomization until objective tumor progression or death. Even if the patient passes away for other reason it counts,
-TIME TO PROGRESSION time from randomization until objective tumor progression. It counts only the day the tumor clearly gets worse on a scan.
KAPLAN MEIER CURVES is an estimate of survival. The statistical analysis tool that allows us to construct the graph of the relationship between the probability of survival and observation time.
How is drug development done?
Carefully designed, reviewed and completed clinical trial.
Need to be approved by an Ethics Committee and must be conducted according to International Ethics Criteria.
5 phases of CTs drive through a logical sequence the development of a new drug/combination or treatment strategy.
SINGLE CENTER or MULTICENTER: in single center the quality is more homogeneous than multicenter, but multicenter CTs reduce selection bias risk, speed up trial duration, increase generalization of the results but require quality control and increase the costs.
What are phase 0 studies?
Very early, first in human trials. Also called micro dosing studies as dose is 1/100 of therapeutic dose. The goal is to assess pharmacokinetics and pharmacodynamics. Optional and not required before phase I.
What are phase I trials?
Define safe dosage range and identify main toxicities. It test new drugs in a small group of patients.
Primary endpoints are : dose limiting toxicity so the highest possible toxicity that prevents further dose increases, maximum tolerated dose so highest dose with acceptable toxicity, and recommended phase II dose.
Secondary endpoints include toxicity profile, biological activity and preliminary anti tumor effects.
Patient criteria include ECOG less than 2, life expectancy less than 3 months, good organ function and advanced disease with no effective treatment option.
What are phase II clinical trials?
The purpose is to asses drug activity. A larger group of patients is tested to assess therapeutic index and low incidence toxicities.
Endpoints : measure activity not efficacy, measured by RECIST. Toxicity, feasibility and tolerability.
What is the difference between activity and efficacy?
Activity (Phase II focus).
Definition: Biological or clinical effect of the drug on the tumor or disease — does it produce a response?
Measured by:
• Response rate (e.g., tumor shrinkage via RECIST)
• Duration of response
• Progression-Free Survival (PFS)
• Biomarker changes
• Goal: Identify whether the drug is doing something meaningful in patients.
• Example: A drug that shrinks tumors in 30% of patients has activity, even if it doesn’t yet prolong survival.
Efficacy (Phase III focus).
Definition: Clinical benefit in terms of patient-centered outcomes — does it improve survival, symptoms, or quality of life?
Measured by:
• Overall Survival (OS)
• Improved Quality of Life (QoL)
• Symptom control
• Goal: Prove the drug actually helps patients live longer or better compared to standard treatment or placebo.
• Example: A drug that doesn’t just shrink tumors but extends median survival by 6 months shows efficacy.
What are phase III clinical trials?
Large, comparative trials which are often international. The purpose is to determine efficacy. Can be double blind or single blind.
Secondary endpoints inlcude toxicity, response rate and correlative endpoints.
What are phase IV clinical trials?
Also called pharmacovigilance. Conducted after approval.
Aim: gather data on long-term safety, cumulative toxicity, and real-world use.
Not mandatory for approval.
Explore efficacy and tolerability in diverse populations.
Success rates in frug development?
Phase I → II: ~44.5% success
Phase II → III: ~19.6% success (highest failure rate)
Phase III → Approval: ~31.2% success
Overall likelihood of approval from Phase I: ~7.9%
