centercenterChamila Alahakoon 2013521620016

centercenterChamila Alahakoon
2013521620016 | ROLE 06LUNG CANCER TREATMENTS AND ONCOTHERAPHY

8820090900Chamila Alahakoon
2013521620016 | ROLE 06LUNG CANCER TREATMENTS AND ONCOTHERAPHY

INTRODUCTION TO LUNG CANCER
Lung cancer ranks no 1 in morbidity world-wide, in men and women.Lung cancer is the leading cause of death in malignant diseases.

DATA BASED ON UNITED STATES OF AMERICA
Lung cancer, also known as lung carcinoma, is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. This growth can spread beyond the lung by the process of metastasis into nearby tissue or other parts of the body. Most cancers that start in the lung, known as primary lung cancers, are carcinomas.

The two main types are ;1.small-cell lung carcinoma (SCLC)
2.Non-small-cell lung carcinoma (NSCLC)
Lung cancer is the leading cause of cancer deaths in the United States, among both men and women. Lung cancer claims more lives each year than do colon, prostate, ovarian and breast cancers combined.

The most common symptoms  are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.
People who smoke have the greatest risk of lung cancer, though lung cancer can also occur in people who have never smoked. The risk of lung cancer increases with the length of time and number of cigarettes you’ve smoked. If you quit smoking, even after smoking for many years, you can significantly reduce your chances of developing lung cancer.

TREATMENTS AND ONCOTHERAPHY
Treatment for lung cancer depends on the cancer’s specific cell type, how far it has spread, and the person’s performance status. Common treatments include palliative care, surgery, chemotherapy, and radiation therapy. Targeted therapy of lung cancer is growing in importance for advanced lung cancer.

lung cancer surgeries

Before surgery we need to know the stages of the cancer and the type:
Small cell lung cancer staging
Small cell lung cancer makes up less than 20 percent of lung cancers and is typically caused by tobacco smoking. It often starts in the bronchi, then quickly grows and spreads to other parts of the body, including the lymph nodes. Small cell lung cancer stages are classified in two ways:
Limited stage: The cancer is found in one lung, sometimes including nearby lymph nodes.

Extensive stage: Cancer has spread to the other lung, the fluid around the lung (the pleura) or to other organs in the body.

Non-small cell lung cancer staging
Non-small cell lung cancer staging uses the TNM system: 
Tumor (T) describes the size of the original tumor.

Lymph node (N) indicates whether the cancer is present in the lymph nodes.

Metastasis (M) refers to whether cancer has spread to other parts of the body, usually the liver, bones or brain.

A number (0-4) or the letter X is assigned to each factor. A higher number indicates increasing severity. The letter X means the information could not be assessed. For instance, a T1 score indicates a smaller tumor than a T2 score. Once the T, N and M scores have been assigned, an overall stage is assigned.

Stages of non-small cell lung cancer:
Occult stage non-small cell lung cancer: Cancer cells are found in sputum, but no tumor can be found in the lung by imaging tests or bronchoscopy, or the tumor is too small to be checked.

Stage 0 non-small cell lung cancer: Cancer at this stage is also known as carcinoma in situ. The cancer is tiny in size and has not spread into deeper lung tissues or outside the lungs.

Stage I non-small cell lung cancer: Cancer may be present in the underlying lung tissues, but the lymph nodes remain unaffected.

Stage II non-small cell lung cancer: The cancer may have spread to nearby lymph nodes or into the chest wall.

Stage III non-small cell lung cancer: The cancer is continuing to spread from the lungs to the lymph nodes or to nearby structures and organs, such as the heart, trachea and esophagus.

Stage IV non-small cell lung cancer: The cancer has metastasized throughout the body and may now affect the liver, bones or brain.

(Data from cancer society of America- https://www.cancercenter.com/lung-cancer/stages/ )If NSCLC, the stage is assessed to determine whether the disease is localized and amenable to surgery or if it has spread to the point where it cannot be cured surgically. CT scan and positron emission tomography are used for this determination.

If mediastinal lymph node involvement is suspected, the nodes may be sampled to assist staging. Techniques used for this include transthoracic needle aspiration, transbronchial needle aspiration (with or without endobronchial ultrasound), endoscopic ultrasound with needle aspiration, mediastinoscopy, and thoracoscopy. Blood tests and pulmonary function testing are used to assess whether a person is well enough for surgery.If pulmonary function tests reveal poor respiratory reserve, surgery may not be possible.
In most cases of early-stage NSCLC, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In people who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However, wedge resection has a higher risk of recurrence than lobectomy.
Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence. Rarely, removal of a whole lung (pneumonectomy) is performed.99 Video-assisted thoracoscopic surgery (VATS) and VATS lobectomy use a minimally invasive approach to lung cancer surgery. VATS lobectomy is equally effective compared to conventional open lobectomy, with less postoperative illness.
(data from Wikipedia-Lung cancer)
“Lung cancer is a heterogeneous, complex, and challenging disease to treat. With the arrival of genotyping and genomic profiling, our simple binary division of lung cancer into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) is no longer acceptable. In the past decade and with the advent of personalized medicine, multiple advances have been made in understanding the underlying biology and molecular mechanisms of lung cancer. Lung cancer is no longer considered a single disease entity and is now being subdivided into molecular subtypes with dedicated targeted and chemotherapeutic strategies. The concept of using information from a patient’s tumor to make therapeutic and treatment decisions has revolutionized the landscape for cancer care and research in general.Management of non-small-cell lung cancer, in particular, has seen several of these advances, with the understanding of activating mutations in EGFR, fusion genes involving ALK, rearrangements in ROS-1, and ongoing research in targeted therapies for K-RAS and MET. The next era of personalized treatment for lung cancer will involve a comprehensive genomic characterization of adenocarcinoma, squamous-cell carcinoma, and small-cell carcinoma into various subtypes. Future directions will involve incorporation of molecular characteristics and next generation sequencing into screening strategies to improve early detection, while also having applications for joint treatment decision making in the clinics with patients and practitioners. Personalization of therapy will involve close collaboration between the laboratory and the clinic. Given the heterogeneity and complexity of lung cancer treatment with respect to histology, tumor stage, and genomic characterization, mind mapping has been developed as one of many tools which can assist physicians in this era of personalized medicine. We attempt to utilize the above tool throughout this chapter, while reviewing lung cancer epidemiology, lung cancer treatment, and the genomic characterization of lung cancer.”(pubmed – Department of Medicine, Section of Hematology/Oncology, NorthShore University Health System, Kellogg Cancer Center, 2650 Ridge Avenue, Evanston, IL, 60201, USA, [email protected] )
Projected incidence and location of relapse following surgical resection in early-stage NSCLC
targeted theraphy

Several drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Erlotinib, gefitinib and  HYPERLINK “https://en.wikipedia.org/wiki/Afatinib” o “Afatinib” afatinib inhibit tyrosine kinase at the epidermal growth factor receptor. Denosumab is a monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand. It may be useful in the treatment of bone metastases.

“Small cell lung cancer (SCLC) accounts for 15% of lung cancer cases and is associated with a dismal prognosis. Standard therapeutic regimens have been improved over the past decades, but without a major impact on patient survival. The development of targeted therapies based on a better understanding of the molecular basis of the disease is urgently needed. At the genetic level, SCLC appears very heterogenous, although somatic mutations targeting classical oncogenes and tumor suppressors have been reported. SCLC also possesses somatic mutations in many other cancer genes, including transcription factors, enzymes involved in chromatin modification, receptor tyrosine kinases and their downstream signaling components. Several avenues have been explored to develop targeted therapies for SCLC. So far, however, there has been limited success with these targeted approaches in clinical trials. Further progress in the optimization of targeted therapies for SCLC will require the development of more personalized approaches for the patients.”(Department of Clinical Research, University of Bern, CH-3010 Bern, Switzerland. Electronic address: [email protected])
“Small-cell lung cancer (SCLC) accounts for almost 15% of lung carcinomas. Chemotherapy is the cornerstone of treatment of patients with SCLC. In limited disease, median survival is about 12-20 months, with no more than 6%-12% of patients surviving beyond 5 years. In extensive disease, median survival is 7-12 months, with < 5% of patients living beyond 2 years and a 5-year survival rate of just 2%. Several therapeutic approaches have been used in an attempt to improve the outcome of SCLC. Among these, a better understanding of tumor biology and the subsequent development of novel therapeutic strategies have been identified as a possible approach for increasing the survival rate of patients with SCLC. Several targeted agents have been introduced into clinical trials in SCLC, and a few phase III studies, including matrix metalloproteinase inhibitors, thalidomide, and vaccines, have already produced definitive results. Currently, negative results are more commonly reported than positive ones. However, this first generation of clinical trials represents only the beginning of clinical research in this field. To date, no targeted therapy has been approved for use in the treatment of patients with SCLC. Nevertheless, clinical research in this field is still in progress considering that several new targeted agents, such as antiangiogenic agents and mammalian target of rapamycin inhibitors, offer a promise of improved outcomes. This review will focus on the reported results and the future development of the main novel biologic agents for the treatment of patients with SCLC.”(New targeted therapies and small-cell lung cancer- Division of Medical Oncology, “S. G. Moscati” Hospital, Avellino, Italy)
IMMUNOTHERAPHY
Current Cancer Immunotherapy:? Vaccine, Cytokine and Adoptive Cell Transfer
Cancer Vaccine
Tumor Antigen + Adjuvant
DC Vaccine
Viral Vaccine
DNA Vaccine
GVAX
Cytokine
IFNa, INFy, IL-2, IL-7, IL-12, IL-15, IL-21
Adoptive Cell Transfer (ACT)
Chimeric Antigen Receptor (CAR)
Genetically Engineered TCR
Tumor Infiltrating T cells (TIL)
NSCLC
Vaccine:
Ag: NY-ESO-1, MAG-3, P53
GV101: hTERT
DRibbles: 9 Ag+TLRTG4010: MUC1
CAR-T:
Mesothelin
VEGFR2
WT1
TCR-T:
NY-ESO-1
MAGE-A3
SurvivinTIL: NSCLC following Chemo
The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.

“Immune checkpoint inhibitors have profoundly altered the therapeutic landscape of several malignancies. The establishment of predictive biomarkers for checkpoint blockades is of the considerable importance in the identification of populations likely to experience a good response to immunotherapy and to maximize the therapeutic benefits. Several trials showed that the tumor mutation burden (TMB) could predict the response to immunotherapy, but some lower clinical benefit was also seen in cancer with high TMB. The imbalance between the strength of immune response and pretreatment tumor burden (TB) could also cause immunotherapy to fail in cancer patients. For this reason, we hypothesized that the TMB-TB ratio could predict the clinical benefit of checkpoint inhibitor immunotherapy and that PFS or ORRs should be used more often in patients with high TMB-TB ratio than in individuals with low TMB-TB ratio”(Tumor mutation burden to tumor burden ratio and prediction of clinical benefit of anti-PD-1/PD-L1 immunotherapy- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200072, China.Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200072, China. Electronic address: [email protected])

RADIOTHERAPHY

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in people with NSCLC who are not eligible for surgery. This form of high-intensity radiotherapy is called radical radiotherapy. A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period Postoperative thoracic radiotherapy generally should not be used after curative intent surgery for NSCLC. Some people with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.

If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage. Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff. Evidence for brachytherapy, however, is less than that for external beam radiotherapy.
Prophylactic cranial irradiation (PCI) is a type of radiotherapy to the brain, used to reduce the risk of metastasis. PCI is most useful in SCLC. In limited-stage disease, PCI increases three-year survival from 15% to 20%; in extensive disease, one-year survival increases from 13% to 27%.

Recent improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiotherapy, high doses are delivered over a number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.
For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy)
Teletherapy
Teletherapy refers to radiation therapy given by an external radiation source at a distance from the body. It is the most common type of radiotherapy used in cancer treatment and is usually given by a Cobalt unit, which delivers high energy gamma rays, or a linear accelerator, which can deliver high-energy X-rays or electrons. In the most common scheme, treatment is given daily for a period of 4-8 weeks.

To deliver an even dose of radiation to the target, which may be several centimeters thick, the radiation source is placed at a distance from the patient (usually 80-150 cm). Healthy tissue, including skin, in the path of the beam can also be irradiated. To reduce this effect, higher-energy beams are used for deeper tumors and treatment is delivered from several angles, which maximizes the dose at the intersection.

Modern teletherapy techniques
Newer techniques, such as 3-D conformal radiotherapy, intensity modulated radiotherapy, and image guided radiotherapy, obtain an extremely accurate shaping of the target that receives the prescribed dose of radiation. These techniques allow radiotherapy to deliver a lower dose of radiation to healthy tissues and a higher dose to the tumor. Patients receiving radiotherapy experience no physical sensation while being exposed to the radiation; it resembles very much having an X-ray. Side effects do, however, occur. In rapidly dividing tissues, such as mucosa and skin, early reactions are similar to ‘sunburn.’ In slow dividing cells, for instance those in the kidney or vasculature supporting the brain and spinal cord, tolerance to radiation is lower. If treated above a certain threshold, they are at risk of developing late effects that usually become apparent many months after treatment.

Modern technology permits considerable geographical sparing of vital organs. Another important tool is radiobiological research that helps select the best treatment schemes. A comprehensive quality assurance programme should be in place.

(Data from – international atomic energy agency )Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

BACKGROUND:
Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.

METHODS:
The biological data gained during these experiments were fed into our previously developed computer model “Cancer and Treatment Simulation Tool” (CaTSiT) to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.

RESULTS:
According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels’ geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor’s therapeutic susceptibility and its metastatic spreading behavior.

CONCLUSION:
Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

(Center for Experimental Medicine, Department of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.)
CHEMOTHERAPHY

When might chemotherapy be used?
Depending on the stage of non-small cell lung cancer (NSCLC) and other factors, chemo may be used in different situations:
Before surgery (sometimes along with radiation therapy) to try to shrink a tumor. This is known as neoadjuvant therapy.

After surgery (sometimes along with radiation therapy) to try to kill any cancer cells that might have been left behind. This is known as adjuvant therapy.

Along with radiation therapy (concurrent therapy) for some cancers that can’t be removed by surgery because the cancer has grown into nearby important structures
As the main treatment (sometimes along with radiation therapy) for more advanced cancers or for some people who aren’t healthy enough for surgery.

Drugs used to treat NSCLC
The chemo drugs most often used for NSCLC include:
Cisplatin
Carboplatin
Paclitaxel (Taxol)
Albumin-bound paclitaxel (nab-paclitaxel, Abraxane)
Docetaxel (Taxotere)
Gemcitabine (Gemzar)
Vinorelbine (Navelbine)
Irinotecan (Camptosar)
Etoposide (VP-16)
Vinblastine
Pemetrexed (Alimta)
Most often, treatment for NSCLC uses a combination of 2 chemo drugs. Studies have shown that adding a third chemo drug doesn’t add much benefit and is likely to cause more side effects. Single-drug chemo is sometimes used for people who might not tolerate combination chemotherapy well, such as those in poor overall health or who are elderly.

If a combination is used, it often includes cisplatin or carboplatin plus one other drug. Sometimes combinations that do not include these drugs, such as gemcitabine with vinorelbine or paclitaxel, may be used.

For people with advanced lung cancers who meet certain criteria, a targeted therapy drug such as bevacizumab (Avastin), ramucirumab (Cyramza), or necitumumab (Portrazza) may be added to treatment as well.

Doctors give chemo in cycles, with a period of treatment (usually 1 to 3 days) followed by a rest period to allow the body time to recover. Some chemo drugs, though, are given every day. Chemo cycles generally last about 3 to 4 weeks.

For advanced cancers, the initial chemo combination is often given for 4 to 6 cycles. Some doctors now recommend giving treatment beyond this with a single chemo or targeted drug, even in people who have had a good response to their initial chemotherapy. Some studies have found that this continuing treatment, known as maintenance therapy, might help keep the cancer in check and help some people live longer.
If the initial chemo treatment for advanced lung cancer is no longer working, the doctor may recommend second-line treatment with a single chemo drug such as docetaxel or pemetrexed, or with a targeted therapy or immunotherapy drug. Again, advanced age is no barrier to receiving these drugs as long as the person is in good general health.

Small cell lung cancer (SCLC)
Chemotherapy is the main treatment for small cell lung cancer. Doctors use it because:
this type of cancer responds very well to chemotherapy
small cell lung cancer tends to have spread beyond the lung when it is diagnosed
Chemotherapy drugs circulate in the bloodstream around the body. So they can treat cells that have broken away from the lung tumour and spread to other parts of the body.

On its own
You might have chemotherapy on its own to treat small cell lung cancer.

Before or after radiotherapy
You might have chemotherapy before or after radiotherapy, or at the same time as radiotherapy.

Before or after surgery
If you are going to have surgery for very early small cell lung cancer, your doctor might suggest that you have chemotherapy before or after your operation
INTREVENTIONAL THERAPHY
The Interventional Pulmonology Program at Cancer Treatment Centers of America® (CTCA) addresses four primary areas:
Central airway obstruction: We use advanced techniques to locate and clear central airway obstructions. This helps you breathe more easily and fully. It also enhances your lung capacity, so you may receive the most aggressive lung cancer treatment regimen possible.

Advanced airway diagnostics: We use imaging technology to look for the cause of symptoms including wheezing, coughing and labored breathing. Our cancer doctors identify tumors, blockages or internal bleeding and use advanced lung cancer treatments to reduce or eliminate symptoms.

Pleural effusion: Many people with lung cancer accumulate excess fluid around the lungs, called pleural effusion. It can cause pain, shortness of breath and other complications. We use minimally invasive techniques to remove this fluid and restore more comfortable breathing. These techniques also help reduce the recurrence of excess fluid in the lungs.

Treatment-related side effects: Some lung cancer treatments, such as chemotherapy, may cause scarring in the lungs. While we try to reduce these side effects, aggressive lung cancer treatment may cause unavoidable complications. We use certain interventional pulmonology procedures to treat your symptoms, and to distinguish between a side effect of treatment and the progression of the cancer.

Bronchoscopy procedures
The lung cancer team at CTCA®  is trained and experienced in delivering advanced, minimally invasive bronchoscopy techniques for many of our interventional pulmonology procedures. Bronchoscopy is a sophisticated technology that uses a flexible tube with a camera at the end (a bronchoscope) that allows us to look inside the lungs and airway.

We use the bronchoscope to deliver laser and other cancer-killing technologies to tumors buried deep inside the lungs. As a result, we can manage symptoms like bleeding or coughing, open up a blocked airway and treat a very early-stage lung cancer or a previously treated area.

Our lung cancer patients benefit from bronchoscopy procedures because they reduce the risks of more invasive treatments.

(data from- American lung cancer society )CONCLUSION :After carefully reviewing and writing and analyzing all the data of lung cancer and its treatments what I felt was it is a very difficult process with lot of time , human sacrifice and it put the patient through emotional, physical and mentally under huge pressure. As well as the family members. For perfume these techniques such as chemo, radiotherapy, interventional therapy takes lots of money and time. So as a conclusion I would like to say that we should need to step up and take necessary actions to stop lung cancer in order to save life’s and to make a better future for human beings.

SUGGESTIONS:
1.STOP SMOKING
2.ISLAND WIDE PROGGRAMS TO SHOW THE SIDE EFFECTS OF SMOKINGS
3.FREE CLINICS FOR PATIENTS FOR CHECK-UPS
4.GOVERMENT INVOLVMENT IN HEALTH PROGRAMMS
5.SUPPORT GROPSORGANISATIONS FOR PEOPLE WHO ARE INNEED OF HELP SUFFERING FROM LUNG CANCER
6.FREE DRUGS FOR PATIENTS
CHAMILA ALAHAKOON
2013521620016
ROLE 06