Stage IV lung cancer: Is cure possible?
Ravi Thippeswamy1, Vanita Noronha1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Thoracic Services, Tata Memorial Hospital, Mumbai, Maharashtra, India
1, Vamshi Krishna1, Amit Joshi1, Munita Meenu Bal2, Nilendu Purandare3, V Rangarajan3, CS Pramesh4, Sabita Jiwnani4, Kumar Prabhash1
Date of Web Publication
Source of Support: None, Conflict of Interest: None
Reporting a case, 53 years old male with stage IV Nonsamall cell lung cancer in view of cytologically proven malignant pleural effusion. Usually the management of stage IV lung cancer is with palliative intent where the patient receives palliative chemotherapy along with palliative radiotherapy and surgery if required. Most of the data on curative management of oligometastatic non-small cell lung cancer includes patient with adrenal metastasis and some reports with brain metastasis. There is scarce literature on the surgical management of stage IV lung cancer with pleural effusion.
Keywords: Chemotherapy, cure, lung cancer, stage IV
How to cite this article:
Thippeswamy R, Noronha V, Krishna V, Joshi A, Bal MM, Purandare N, Rangarajan V, Pramesh C S, Jiwnani S, Prabhash K. Stage IV lung cancer: Is cure possible?. Indian J Med Paediatr Oncol 2013;34:121-5
How to cite this URL:
Thippeswamy R, Noronha V, Krishna V, Joshi A, Bal MM, Purandare N, Rangarajan V, Pramesh C S, Jiwnani S, Prabhash K. Stage IV lung cancer: Is cure possible?. Indian J Med Paediatr Oncol [serial online] 2013 [cited 2016 Feb 6];34:121-5. Available from: http://www.huonvalley.biz/?p=250
Lung cancer is one of the common differential diagnosis for, weight loss, lung mass, pleural effusion with lymphadenopathy in a male smoker in our country.The diagnosis requires high index of suspicion as it can be easily confused with tuberculosis and chronic bronchitis.The standard management of stage IV lung cancer with good performance status is palliative chemotherapy. Here we would like to discuss surgical options for oligometastic stage IV lung cancer with pleural effusion.
A 53-year-old male, chronic smoker, presented with history of left-sided dull aching chest pain for 1 month and significant weight loss of 5 kg in 1 month. There were no symptoms of breathing difficulty, hemoptysis, bony pains, or lumps noticed anywhere in body. Evaluation included a contrast-enhanced computed tomography (CT) of thorax which revealed a left upper lobe peripherally situated mass of size 2 2 cm involving chest wall, enlarged pretracheal, prevascular, and aortopulmonary window nodes, and mild left pleural effusion.
Differential diagnosis and diagnostic evaluation recommended
The common differential diagnoses for weight loss and lung mass with lymphadenopathy in a male smoker in our country are chronic obstructive lung disease, chronic bronchitis, tuberculosis, pneumonia, and lung cancer. Clinical history and thorough examination should be made with careful palpation of the neck for lymphadenopathy and chest auscultation. A chest radiograph is the basis of imaging and is complemented by a contrast-enhanced CT scan of the chest, which should include the liver and the adrenal glands. Tissue diagnosis is mandatory if the clinicoradiological suspicion of malignancy is high and a biopsy should be performed either by bronchoscopy or with CT guidance. If confirmed to be malignant, further staging workup would be required if the chest CT scan shows non-metastatic disease. A metastatic workup would include a positron emission tomography (PET)-CT scan and a magnetic resonance imaging (MRI) scan of the brain.
Our patient presented to us with a CT scan showing a left upper lobe mass with ipsilateral mediastinal lymphadenopathy and a small pleural effusion. His vitals were normal, physical examination was unremarkable, and ECOG performance status was 1. Fiber optic bronchoscopy showed no endobronchial growth. Diagnostic thoracentesis was performed. Pleural fluid cytology was positive for metastatic squamous cell carcinoma.
Role of cytology in lung cancer
Conventional cytologies such as sputum examination, bronchial lavage, bronchial brushings, fine-needle aspiration biopsy have played an important role in the diagnosis of primary and metastatic lung cancers. Immunohistochemical stains can be applied on cytological material. The immunohistochemical markers such as TTF-1, CK7, CK20, 4A4, 34 E12, and p63 help to classify further subtypes in Non-small cell lung cancer (NSCLC). In addition, epidermal growth factor receptor (EGFR) gene mutation studies can also be done on the blocks prepared from cytological material, which helps in choosing appropriate targeted therapy. Thus, cytology plays an important role not only to subclassify tumors but also to individualize treatment strategy with the advantage of easy availability and minimum invasiveness. 
Thus, the patient was diagnosed with squamous cell carcinoma of the lung, T3N2M1a, stage IV.
The standard management of stage IV lung cancer is palliative chemotherapy with platinum-based combination chemotherapy. However, there are some reports of patients with lung cancer with only a malignant pleural effusion and no other metastatic sites that have long-term cures with chemotherapy and surgery. , In view of the excellent performance status of the patient and the PET-CT showing no other sites of metastases, it was decided that therapy with potentially curative intent could be attempted even though this would be a deviation from established guidelines. A staging workup was performed.
Staging evaluation of lung cancer
After establishing a tissue diagnosis, a complete staging workup is done to identify the presence of metastasis and for feasibility of surgical resection.
After detailed history and physical examination, laboratory investigations such as complete blood count, liver function tests (transaminases), serum electrolytes, serum calcium, and serum alkaline phosphatase are done. More than 80% of patients with an abnormality on evaluation have metastatic disease. Patients presenting with anorexia, weight loss, and fatigue have an especially poor prognosis which depicts advanced stage and aggressive tumor biology. 
Chest and abdomen CT and PET scans are routinely performed in patients with suspected metastatic lung cancer. Chest and upper abdomen CT scans help to identify hilar and mediastinal adenopathy and liver or adrenal metastases. CT chest has accuracy of 88% (80% sensitive and 100% specificity) in identifying mediastinal involvement. Integrated CT/PET has better sensitivity and specificity than CT or PET alone. 
Bronchoscopy with or without transbronchial needle aspiration, endobronchial ultrasound-guided transbronchial needle aspiration, video-assisted thoracoscopy, or mediastinoscopy has played an important role in evaluation of patients with suspected mediastinal involvement. Video-assisted thoracoscopy or mediastinoscopy has the advantage of directly visualizing the lesion and accurate sampling. Additional investigations are performed depending on clinical symptoms. Bone scanning and brain magnetic resonance imaging may be performed, depending on symptoms. 
PET/CT has good sensitivity and specificity in identifying distant metastases.  Thus, the PET/CT is very important in the decision-making process for a patient with NSCLC, especially so in a patient with oligometastases. Any suspicious lesion identified by PET/CT should be confirmed by histopathological evaluation. Various studies have reported that whole body PET detects occult metastases in 6-17% of NSCLC patients in whom conventional staging methods failed to identify the metastases.  PET/CT has positive predictive value of 54% in identifying additional lesions on top of the primary lung cancer. 
A PET-CT scan and an MRI scan of the brain showed absence of metastatic disease. The patient was counseled in detail regarding the standard recommended treatment of palliative chemotherapy alone, or an off-guideline option of chemotherapy followed by surgery if the response was good. The patient chose the latter option. The patient was given three cycles of chemotherapy with gemcitabine 1000 mg/m 2 day 1 and day 8 along with carboplatin AUC 5 (area under the curve, calculated by Calvert formula) on day 1 for every 21 days. He tolerated the chemotherapy well without major side effects. There was significant symptomatic benefit in the pain after the first cycle of chemotherapy.
Following three cycles of chemotherapy, PET-CT revealed a 1.9 1.6 1.2 cm left lingular lobe mass (SUV 3.5) with no abnormal activity in the mediastinal nodes and no distant metastases. We performed a left upper lobectomy with systematic mediastinal lymphadenectomy following which the patient had an uneventful post-operative recovery. Intra-operatively, a 2 2 cm left upper lobe lung mass was seen adherent to the pericardium with enlarged aortopulmonary AP window and left hilar nodes. There were no pleural nodules or effusion. The final histopathology showed no residual tumor with all regional nodes negative for metastasis (ypT0N0) [Figure 1].
Figure 1: Microscopy revealed large areas of necrosis, lymphoplasmacytic infiltrate, and hemosiderin deposits amidst areas of fibrosis. No residual tumor was identified (H and E, original magnification, ×100)
The patient is now alive and free of disease after a 24-month follow-up.
Assessment of pathological response to chemotherapy has played an important role in head and neck carcinomas, esophageal carcinoma, osteogenic sarcoma, and small cell lung carcinoma. Pathological complete response is defined as fibrosis or fibro inflammation without microscopic evidence of carcinoma and histologically negative nodes. Non-pCR is defined as any evidence of viable carcinoma, either at the primary site or at the resected regional LN. Those patients who achieve complete pathological response have long-term survival advantage. Junker et al.  found that in NSCLC patients, not only complete responders but also extensive responders with 10% residual tumor also had good long-term survival.
The common histological features of tumor regression are coagulative necrosis, fibrosis, foam cell/giant cell reaction, as well as mixed inflammatory infiltrate. The amounts of fibrosis correlate well with extent of tumor regression, which in turn is a surrogate marker of tumor response. Squamous carcinoma was associated with a higher probability of treatment response than adenocarcinoma. 
To conclude, pathological response can be of two types: Responder and non-responder groups. The common histological changes seen are fibrosis, necrosis, and foam cell/giant cell reaction; in some cases, increase in residual tumor nuclear grade is seen. The radiological assessments may not correlate well with the pathological response. 
NSCLC is the leading cause of cancer-related deaths worldwide. Brain, bone, liver, and adrenal gland are the most common extrapulmonary sites of distant metastases.  20-50% of NSCLC will present with metastatic disease. Stage IV NSCLC cancer has an overall median survival time of 7-11 months. 
In the past, patients with stage IV disease were generally believed to be incurable. Patients with oligometastatic disease represent a distinct subset. After full evaluation, approximately 7% of patients with metastatic disease will have solitary metastasis. , There is evidence that in such patients, survival benefit can be achieved with surgical resection. 
Accurate clinical staging is of utmost importance before embarking on curative surgery. FDG-PET/CT plays an important role in decision making and should be done if radical treatment is considered. The overall 5-year survival rate is about 28% for patients with satellite nodules and 21% for patients with ipsilateral pulmonary nodules. In patients with brain metastases, surgical resection achieves 5-year survival rates between 11% and 30%, and those with adrenalectomy for adrenal metastases have 5-year survival rates of 26%. 
Most of the data on curative management of oligometastatic NSCLC include patient with adrenal metastasis, brain metastasis, and few selected reports of patients with lung cancer with only a malignant pleural effusion and no other metastatic sites who have long-term cures with chemotherapy and surgery. ,
Brain metastases have dismal prognosis without treatment, with median survival of 1-2 months.  Historically, whole brain radiation therapy (WBRT) was the standard of care in the management of brain metastases. 75% of patients had symptomatic neurological improvement with WBRT alone. However, this benefit is short-lived, with a median survival of only 3-6 months. Chronic neurological morbidities were seen in significant patients on follow-up.  With advances in surgical techniques, resection of solitary brain metastasis can be done with low surgical morbidity and mortality rates (0-3%). 
Stereotactic radiosurgery is an alternative approach to surgical resection in which high dose of focused radiation in a single fraction to a specific intra-cranial target is delivered, thus minimizing the unwanted radiation exposure to normal surrounding parenchyma. Recent data suggest that the combined treatment regime is beneficial for patients with a single brain metastasis. ,
The adrenal gland metastatic involvement ranges from 18% to 42% in an autopsy series. , Benign adenomas (2-9%) are common in general population, so the presence of an adrenal mass on imaging itself does not confirm metastasis. , The prognosis and management depend on whether the mass is benign or malignant. PET-CT and an MRI do not definitively rule out malignancy, , so histopathological confirmation is must before lung resection. The potential benefit of diagnostic laparoscopy over fine-needle biopsy alone is that it allows the exploration of the entire peritoneal cavity with a histological examination of suspected nodules. , Moreover, laparoscopic adrenalectomy done for diagnostic purposes is itself a therapeutic modality for metastases. 
Other extrathoracic metastases
In NSCLC, most common sites for oligometastatic disease include the thorax, adrenals, and brain; metastases other than these sites are rare. There are two retrospective case series addressing this issue. , Long-term survival was high, with a 5-year overall survival rate of 55.6% and a 10-year overall survival rate of 86% in reported series , Based on the above two retrospective studies, three factors are considered important in selecting patients for resection: (a) the primary tumor should be completely resected; (b) metastases must be metachronous onset; and (c) there should be no other distant metastasis. 
Our patient was treated as stage IV NSCLC with curative intent as a deviation from established guidelines. In the absence of other distant metastases, he was given three cycles of neoadjuvant chemotherapy and underwent curative intent surgery. Complete pathological remission was achieved which has been rarely reported in literature.
The diagnosis of malignant pleural effusion with non-small cell carcinoma does not necessarily imply that patient has incurable disease. In selected subsets of patients, a cure may be possible after multimodality therapy. To properly select patients for an aggressive local treatment regime, accurate clinical staging is of prime importance. The use of FDG-PET should be considered for restaging if oligometastatic disease is suspected based on a patient’s CT scan. Our case report illustrates the potential role of curative intent surgery in stage IV lung cancer, with malignant pleural effusion but without distant metastases. The usefulness of PET-CT imaging in the staging and evaluation of response are also highlighted by the current study.
Cancer is costly. It can take a toll on your health, your emotions, your time, your relationships – and your wallet. There will be unexpected charges, and even the best health insurance won’t cover all your costs. Here are some tips on what costs you can expect and some ideas on how to plan for, ask about, and discuss treatment costs with your cancer care team. Don’t wait until you have financial problems to discuss cancer costs with your health care team.
You might feel as if you don’t have the energy to deal with cancer and talk about money, too. You might want to ask a friend or family member to keep track of costs for you. Ask this person to go with you to doctor visits and help with these discussions.
Learn as much as you can about cancer and your cancer treatment before it starts. This will help you know what to expect. It can also help you plan for and deal with the costs. Many people with cancer have medical expenses for things like:
Talk with the people on your cancer team. They’ll usually know who can help you find answers. Here are some questions you can ask about costs. Choose the ones that relate to you and your treatment.
Here are some ideas for ways to bring up the subject of cost as your treatment is planned:
Some related or follow-up questions you might want to ask:
Today, more and more chemo drugs are taken by mouth. (This is often called oral chemo, and includes drugs known as targeted therapy.) In most cases, this means you get a prescription and take the drugs on your own, at home.
Chemo taken by mouth is as strong as the other forms and, when taken properly, works just as well. But oral chemo drugs cost a lot – sometimes many thousands of dollars each month. And most health insurance plans don’t pay for the oral drugs the same way they pay for the IV drugs (those put into a vein in the hospital, clinic, or office).
Oral chemo drugs are often treated like regular prescription drugs. You have to pay for them and, even if your insurance covers them, you might have a very high co-pay. For example, some insurance companies require a co-pay of 25% of the drug cost. This can be thousands of dollars. And this isn’t a bill that you can pay later – you have to pay when you pick up the drug at the pharmacy.
Make sure you know how much you’ll have to pay for each treatment. Many drug manufacturers have patient assistance plans to help people pay for their drugs. Ask your cancer care team about this.
Please see If You Have Problems Paying a Medical Bill or call us to learn more about this.
Many kinds of drugs are used to treat cancer. These may be drugs to prevent nausea, treat pain, help with anxiety, or control diarrhea. Drug prices vary a lot. You (or a family member) may want to call different pharmacies to get an idea of where you can get the best price.
When your doctor prescribes medicines or outpatient care, here are some questions you may want to ask:
If you must have surgery, chemo, radiation, or will be in the hospital for part of your treatment, here are some questions you might want to ask:
Out-of-pocket costs are costs you have to pay because your health insurance doesn’t. They can add up quickly and may make it hard for you to pay for other things you need.
You’ll want to be sure that your health insurance company pays or reimburses the bulk of your medical expenses. This means you’ll need to
If any of your treatments might be done by out-of-network doctors or providers, find out about those costs, too. Even when you know the terms of your policy, getting payments can mean re-submitting claims, appealing denials, and much more.
Usually, doctors’ offices and clinics have someone who handles health insurance concerns and problems. Ask your doctor if that person can help you with claims and codes on the bills that are sent to the insurance company.
You can find out more about health insurance and other costs at Understanding Health Insurance.
Our health insurance experts are also available to answer your questions 24 hours a day, 7 days a week. You can reach one of them by calling 1-800-227-2345.
We have a lot more information that you might find helpful. Explore www.cancer.org or call our National Cancer Information Center toll-free number, 1-800-227-2345. We’re here to help you any time, day or night.
American Society of Clinical Oncology (ASCO)
Web site: www.cancer.net
Has a special section for patients on the costs of cancer care at www.cancer.net/managingcostofcare. Also offers cancer and cancer-related information (including many in Spanish), on things like treatment, side effects, coping, and survivorship, as well as a database to help find an oncologist
Patient Access Network Foundation (PANF)
Toll-free number: 1-866-316-7263
Web site: www.panfoundation.org
Helps under-insured patients with certain cancer diagnoses cover out-of-pocket costs related to cancer care.
Patient Advocate Foundation (PAF)
Toll-free number: 1- 800-532-5274
Web site: www.patientadvocate.org
Works with the patient and their insurer to resolve insurance problems; also provides direct financial support to insured patients who are financially and medically qualified for drug treatments and/or prescription co-pays, co-insurance, and deductibles related to certain cancer diagnoses.
American Society of Clinical Oncology. Managing the Cost of Cancer Care. Accessed at www.cancersupportcommunity.org/MainMenu/About-Cancer/Understanding-Cancer/Coping-with-the-Cost-of-Care/Where-do-I-begin.html on October 30, 2015.
Bestvina CM, Zullig LL, Yousuf Zafar S. The implications of out-of-pocket cost of cancer treatment in the USA: a critical appraisal of the literature. Future Oncol. 2014;10(14):2189-2199.
Bullock AJ, Hofstatter EW, Yushak ML, Buss MK. Understanding patients’ attitudes toward communication about the cost of cancer care. J Oncol Pract. 2012;8(4):e50-58.
Cancer Support Community. Frankly Speaking About Cancer: Coping with the Cost of Care, 5 edition. Accessed at www.cancersupportcommunity.org/General-Documents-Category/Education/FSAC-Coping-with-the-Cost-of-Care.pdf on October 30, 2015.
Peppercorn J. The financial burden of cancer care: do patients in the US know what to expect? Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):835-842.
Tangka FK, Trogdon JG, Richardson LC, et al. Cancer treatment cost in the United States: has the burden shifted over time? Cancer. 2010;116(14):3477-3484.
Ubel PA, Abernethy AP, Zafar SY. Full Disclosure – Out-of-Pocket Costs as Side Effects. N Engl J Med. 2013;369(16):1484-1486.
Many individuals desire to improve their brain function and also memory retention however are not positive how to start. It’s wise for a person to start out simply by transforming the way that they eat and working towards a healthier way of life to begin with. A healthy diet is going to increase the person’s health overall, together with their brain function and also memory retention. This doesn’t mean letting go of pretty much everything which is scrumptious and sticking to vegetables, it implies eating things in moderation and being mindful to take in adequate nutrients daily without overloading the body with excess calories.
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These days, it appears like smoothies are the new thing when it comes to health and fitness. Health experts honor smoothies for their own power to play a role in a nutritious diet as well as weight loss. Even so, the ability to produce a fantastic smoothie is based a great deal regarding the sort of blender an individual uses. Even though you may discover a fantastic discount vitamix machine you will find a range of factors that needs to be considered.
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The picture of surgical landscape has changed vividly over past few decades. Advances in the field of minimally invasive surgery aims at delivering quality surgical results without large incisions and without the risk of injury to the surrounding structures that typically happens in traditional surgeries. Lungs cancer treatment in India at any stage particularly in early stage (stage I, II) and even stage III is more successful as minimally invasive surgery is done through VATS (video assisted thoracic surgery) that provides many advantages for the patient suffering from lung cancer.
Cancer happens when the cells in a part of the body grow abnormally faster and in uncontrolled manner due to mutation in the DNA of the cells. Similarly cancer in the lungs happens when the cancer cells invades the lungs and destroy the healthy cells of the lungs thereby hindering the normal functions of the lung. Cancer in lungs may take several years to develop.
At times, these cancer cells may spread to affect other parts of the body through metastasis.The lungs cancer often go unnoticed in early stages as it hardly produces any symptoms. The advanced cancer may show up symptoms like blood in the cough, persistent cough, chest pain, hoarseness in the voice, recurrent chest infection etc. There are two main types of lungs cancer;
The staging of the lung cancer is essential in order to know the extent of the spread of disease and make the treatment plan accordingly. The lung cancer is thus staged as:
Localized: cancer is confined to lungs
Regional: cancer has spread to lymph nodes in the chest
Distant: cancer has spread to other parts of the body.
Following are the risk factors that are responsible for developing the lung cancer.
Treating lung cancer is very challenging. To regulate the survival rates, it is essential to know the stage of the disease. The treatment for the lung cancer can either be curative in which the interventions are done to control the growth of the cancer, or it can be palliative, which aims to improve the quality of life by managing pain and associated symptoms.
These procedures are done using minimally invasive VATS technology that involves insertion of thin tube that is attached to the thorascope (camera) and the specialized small surgical instruments to carry out the required surgery. The thorascope provides images on the monitor using which the surgeon removes the tissue with more ease and precision.
If you are suffering from any of the symptoms mentioned above, you should see a doctor immediately who would advise you various tests for correct diagnosis. If you are diagnosed with lungs cancer, the treatment should be started immediately.
Surgery is indicated in most of the cases of lungs cancer. Depending on the size, location and extent of spread of the tumour, either wedge/ segmental resection, lobectomy or Pneumonectomy procedure is performed to excise the tumour and tissues surrounding it. These procedure are now being performed using the minimally invasive VATS approach.
The surgery is done under general anaesthesia. Surgeon makes several 2-4cms small incisions on the chest between the ribs. Using the thorascope (camera) that is put inside the chest cavity, the surgeon evaluates the cancerous lung tissue by looking on the images on the monitor from the camera. After evaluating with the help of specialized surgical instruments that have been put inside through one of the incisions, the surgeon transects and removes the required amount of tissue from the lung.
Advantages of VATS or Minimally invasive surgery:
Recovery after the surgery to a large extent depends on the type of surgery performed. After minimally invasive procedure, the patient can be discharged after 3-4 of the surgery and can resume work and normal activities within 4-5 weeks after the surgery.
One can experience improvement in quality of life after undergoing the treatment. Moreover, minimally invasive surgery helps patient lead life with less pain after the surgery, better immunity and better chance of normal breathing and comparatively less time of recovery.
The time required for lungs cancer treatment in India depends upon the stage of cancer. If only surgery is required, the patient would need 2-3 weeks for lungs cancer treatment in India. However, if radiotherapy and chemotherapy are also required, several weeks may be required.
At IndiCure, we recognize the significance of excellent health and well-being of our guests and hence our objective is to provide best lung cancer treatment in India at honest affordable prices. A preferred association with best hospital for lung cancer treatment in India and top surgeons in India helps us advise:
The cost of chemotherapy in India depends upon various factors such as the patient’s medical condition, city and the facility where you choose to get the procedure done.
An individually allocated case manager takes personalized interest to design a tailor made treatment plan for every guest and will provide with a specific time and cost of chemotherapy in India.
Medical history and diagnostic reports may be sent to firstname.lastname@example.org for an early response from the case managers.
We encourage you to educate yourself about lung cancer treatment in India, benefits from the right kind of procedure and then make an informed decision.
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