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Lung Cancer

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Philip Yeung

on 1 October 2013

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Transcript of Lung Cancer

Lung Cancer

Learning Objective
Disease Epidemiology
Screening and Diagnosis
Disease Pathophysiology and Staging
Clinical Presentation
Treatment options
Potential Treatment Pitfalls

Pathophysiology and Staging
Non-Small Cell Lung Cancer Treatment
Stage 3-4 Treatment
Disease Epidemiology
Screening and Diagnosis
ALK & EGFR Mutations
Patients with an ALK (anaplastic lymphoma kinase) or EGFR (epidermal growth factor receptor) mutation in stage IV lung cancer will be treated regardless of their performance scale.
Patients with an ALK gene mutation will receive crizotinib as a first line therapy.
Crizotinib: inibitor of receptor tyrosine kinases, including ALK
Patients with an EGFR will receive erlotinib as a first line therapy.
Erlotinib: small molecule tyrosine kinase inhibitor which acts on EGFR

First Line Therapy
Lung Cancer is the leader cause of cancer death
In 2009
205,974 people in the United States were diagnosed with lung cancer, including 110,190 men and 95,784 women.
158,081 people in the United States died from lung cancer, including 87,694 men and 70,387 women.
Risk Factors
Being greater than or equal 65
Tobacco Smoking
History of Cancer
Contact with Cancer-Causing Agents
Infectious Disease of the Lung
Previous history of lung disease

CT and PET scans are used to screen for nodules
Nodules can be broken down into two groups
Non-solid nodule
Low density
Solid-nodule
High density
Nodules are more likely to be cancerous if either tissue inflammation are scarring are found.

Pathophysiology
Lung Cancer starts off as carcinomas that line the airways of the lungs
Two types of Lung Cancer
Non-Small Cell Lung Cancer
More common
Can be subdivided into
Squamos Cell Carcinoma
Large Cell Carcinoma
Adenocarcinoma
Small-Cell Lung Cancer
Usually closely associated with inhalation of smoking
Less Common
Usually more aggressive
Stage 1-2 Treatment
Stage 1-2 Non-Surgical Treatments
Many patients are not candidates for surgery due to comorbid conditions or location of tumor
Radiation therapy takes the place of surgery in these patients
Cure rates lower for radiation therapy
Chemotherapy may be used with radiation therapy

Stage 3a Treatment
Stage 2b with T3 and N0 groupings should follow stage 3 treatment guidelines
Based on location of tumor and extent of regional lymph dose involvement
If no mediastinal lymph node involvement (N</=1), surgery is the primary treatment
Neoadjuvant therapy (either chemoradiation or chemotherapy) is recommended for some tumor sites (tumors of proximal airway, mediastinum, and apex of lung)
Adjuvant chemotherapy recommended regardless of tumor site

Stage 3b and 4
2/3 of patients present with this stage
Majority are of these advanced tumors are nonresectable
Patients with a single metastic site may undergo surgical resection of both the tumor and metastatic site
Chemotherapy treatment is first line
Intent is to palliate symptoms, improve quality of life, and increase duration of survival

Determining First Line Therapy
With first line therapy, determine if it is squamous cell carcinoma or non-squamous cell carcinoma.
Then access patient’s performance status (0-4) to determine how aggressive you will be treating the tumor.
There are two exceptions to using the performance scale
EGFR or ALK Mutation

ECOG Performance Scale
ECOG scale determines how much chemotherapy a patient can handle based on their physical performance and health.
Scaling is from a 0-4
Score of a 0 means you are fully active and healthy and can handle the strongest form of chemotherapy.
Score of 1 may mean you are not fully healthy but can still provide your own self care thus you can still handle aggressive therapy.
Patient’s having a score of 2 means you are unable to exert any physical activity and are generally given less extensive chemotherapy.
A score of a 3 or 4 means you are nearly disabled and should not receive any chemotherapy. These patients should only receive palliative care.

Double and Single Therapy Options
Doublet options: 4-6 cycles
Cisplatin + one of the following:
Vinca alkaloids (vinorelbine and vinblastine)
Taxane (paclitaxel and docetaxel)
Gemcitabine
Pemetrexed
Etoposide
Single Therapy: Docetacel, Pemetrexed, or Erlotinib

If cancer grows during or after first line treatment…
If cancer does not grow during first line chemotherapy ...
Then maintenance therapy follows after.
Maintenance therapy is determine based on what first line therapy was given.


Based on Jim Harvey's speech structures
Biopsies
If nodule is cancerous, biopsies are taken
Five different biospies
Standard Bronchoscopy
Radial EBUS (Endobronchial Ultrasound) Bronchoscopy
Navigational bronchoscopy
TTNA (Transthoracic Needle Aspiration)
Open Surgery Biopsy

Staging
TNM Score
T Score (1-4)
How larger or where the primary tumor has grown
N Score (0-3)
If the cancer has spread from the originating node to another node
M Score (0-1)
If the cancer has spread to a distance site or not.

Surgery is the mainstay of treatment
Lobectomy typically used for stage 1
Pneumonectomy for stage 2 with lymph node involvement
Stage 1a: treated with surgery alone
If surgical margins are positive, re-resection recommended
Stage 1b-2b: surgery should be followed by adjuvant chemotherapy
Adjuvant radiation therapy can be used in patients with positive or questionable margins
Should not be used in patients with clear margins

Adjuvant Chemotherapy Options
Cisplatin therapy in combination with one of the following:
Vinorelibine, etoposide, vinblastine, gemcitabine, or docetaxel
Cisplatin plus vinorelbine has shown the results
For patients not able to take cisplatin:
Paclitaxel combined with carboplatin

Doublet options: 4-6 cycles
Cisplatin + one of the following:
Vinca alkaloids (vinorelbine and vinblastine)
Taxane (paclitaxel and docetaxel)
Gemcitabine
Pemetrexed
Etoposide
Single Therapy: Docetacel, Pemetrexed, or Erlotinib

First Line Therapy Continued
Double platinum therapy: is always preferred over a single agent, however, double therapy tends to have more side effects.
Gemcitibine + either Pacitaxel or Docetaxel is used in patients with platinum allergy
Following 2 cycles of chemotherapy, the cancer will be tested to see if it has responded to treatment.
If there is no cancer growth, patient will continue receiving first line therapy for another 4-6 cycles and will then be tested again.
If cancer growth is detected, patient will receive alternative therapy…

Pitfalls to Treatments
Pitfalls of Chemotherapy
Patient may have a hypersensitivity to platinum derived drugs (cisplastin or carboplatin). If this is the case, patient should receive alternative form or therapy.
The downfall of alternative therapy is it may not be as effective and may lead to more side-effects.
Cisplastin is preferred over carboplatin, however, if patient cannot handle cisplastin, carboplatin is used with paclitaxel as 3 full dose cycles following local treatment.
Side effects of cisplatin are neurotoxicity, peripheral neuropathy, nausea, vomiting, anemia, leukopenia, and thrombocytopenia.

Targeted Chemotherapy Pitfalls
With any of the monoclonal antibodies (cetuximab and bevacizumab) severe hypersensitivity could occur and patients should be monitored during first time administering.
All antibodies should be taken with caution in anyone with a cardiovascular condition.
Patients who have coughed up blood before (hemoptysis) should not take bevacizumab.

Small Cell Lung Cancer Treatment
Responsive to radiation & chemotherapy.
For most patients chemotherapy with or without radiation is first line therapy.
Treatment method is chosen based off of:
stage (limited vs extensive)
patient age
performance status
comorbid conditions
patients will to receive treatment.

Stage: Limited Disease
Single SCLC -> local surgery or radiation (more common)
Radiation alone has poor cure rate therefore systemic chemotherapy is also used.
1st Line: etoposide-cisplatin (EP) plus thoracic radiotherapy
Maximum of 4-6 cycles
Alternative: carboplatin instead of cisplatin to decrease N/V, neurotoxicity and nephrotoxicity (can result in thrombocytopenia from increased myelosuppression)
Chemoradiotherapy leads to best survival rates
Prophylactic cranial irradiation (PCI) is recommended in patients that achieve a complete treatment response
Study showed PCI increasing 3 year survival from 15% to 21% by reducing incidence of brain metastasis.
Recurrent Disease
Less sensitive to chemotherapy
Refractory SCLC: less than 3 months between chemotherapy and relapse
Second line therapy won’t be effective
Supportive care or clinical trial
Patients with greater than 3 months between chemotherapy and relapse-> treatment is recommended
Only FDA approved second line therapy: topotecan (PO or IV)
Topotecan only has modest efficacy therefore other therapies include: irinotecan, gemcitabine, paclitaxel, docetaxel and vinorelbine.

Therapeutic Outcomes Evaluation
Evaluate effectiveness of therapy after 2-3 treatment cycles.
After 2-3 treatment cycles:
Continue therapy for patients with partial or complete response, or stable disease
D/C of switch to non-cross-resistant regimen in patients with progressing disease
If chemotherapy is responsive, regimen is given for 4-6 cycles.
After completing therapy:
PCI is recommended
Follow up every 3 months for first three years, every 4-6 months for fifth and sixth year, and yearly in patients with partial or complete response.

Stage: Extensive Disease
1st Line: etoposide-cisplatin (EP)
Maximum of 4-6 cycles
Alternative: irinotecan and cisplatin
Radiotherapy isn’t usually used concurrently with systemic chemotherapy
Prophylactic cranial irradiation is recommended for patients responding to chemotherapy
Study showed PCI increasing 1 year survival from 27.1% to 13.3% by decreasing brain metastasis from 40.6% to 14.6%.

Frieze DA, Adams VR. Chapter 137. Lung Cancer. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill, 2011;2168-2169

Patient Case
Patient WW, 65 year old, male reports to PCP for annual checkup
CC: Wheezing, SOB, pain while coughing
PMH: COPD (past 10 years)
FH: Mother was a former smoker who died of Lung CA 5 yrs ago
SH: High School chemistry teacher

PCP refers him to hospital for further workup

Pertinent Lab Findings:
Na: 139mEq/L (135-145mEe/L)
K: 2.8mEq/L (3.5-5mEq/L)
Ca: 11.7mg/dl (8.4-10.2mg/dL)
PET scan reveals dense nodule found in upper right lobe of lung
Doctor suspects it’s cancer and does a biopsy that’s still pending

Diagnosis
Biopsy results are indicative of Non-Small Cell Lung Cancer (Squamous cell carcinoma)
Chest X-Ray: Tumor is approx. 2cm in diameter and is spread around the mediastinum node.
Patient AB is diagnosed with Stage III NSCLC

Labs
History

Stage 3a Treatment Continued
Patients staged as 3a with N</=1 who are not candidates for surgery:
Treat with a platinum containing chemotherapy regimen plus radiation
Patients who respond well may then become surgical candidates
If mediastinal lymph node involvement (N>/=2):
Treat with both a platinum containing chemotherapy plus radiation therapy

Shahjabin Kureshi
Liz Lakota
Jacob Reaser
Philip Yeung

Presented by....
References
Frieze DA, Adams VR. Chapter 137. Lung Cancer. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill, 2011;2168-2169
Douillard JY, Tribodet H, Aubert D, Shepherd FA, Rosell R, Ding K, et al. Adjuvant cisplatin and vinorelbine for completely resected non-small cell lung cancer: subgroup analysis of the Lung Adjuvant Cisplatin Evaluation. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2010;5(2):220-8. doi: 10.1097/JTO.0b013e3181c814e7.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA: a cancer journal for clinicians. 2010;60(5):277-300. doi: 10.3322/caac.20073.
NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. National Comprehensive Cancer Network; 2013 [cited 2013 September 22]; Available from: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.

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