Concepts: Non-small cell lung cancer treatment, staging, chemotherapy, surgery, and radiation for non-small cell lung cancer,  

CHAPTER FOUR NON-SMALL CELL LUNG CANCER

4.1 OVERVIEW

The material below has been excerpted from the National Cancer Institute website with some limited editorial revision. Since the type of treatment, use of surgery, chemotherapy and radiation depends upon stage, the chapter is divided by stage. Surgery is the major potential curative option for early diagnosed patients with smaller tumors and no lymph node involvement or metastatis. For others, radiation and chemotherapy provides varying results with those results deliniated below. The fact that survival is so directly related to early diagnosis is a compelling argument for screening programs to identify those at high risk at an early stage. At present, screening programs are rarely used.

4.11 Advice for the Reader

The material NCI (National Cancer Institute) provided is excellent, but the reading can at times be difficult. Try to read each section slowly and consult the definitions at the end of the book, and have a medical dictionary on hand. If you are able to digest the information here, you may be able to reduce the general information which takes up a lot of time in doctor-patient conferences, understand your condition and the treatment which is being provided, and be able to ask some pointed questions about your disease with the information you have learned.

4.12 Summary

The book, Lung Cancer, has an excellent summary of the different stages of lung cancer which is useful to review before studying the NCI materials:

Stage 1 (T1 N 0 MO or T2 N0 M0) These patients have T1 or T2 carcinomas but no metastasis to lymph nodes or distant organs. They are candidates for curative resection with a very favorable prognosis.

Stage 2 (T1 N1 M0 or T2 N1 M0) These patients have T1 or T2 carcinomas but also have pulmonary node metastasis (N1) Hilar hymphadeonopathy may require pneumonectomy (removal of the lung) for curative resection, and as a result,seom patients with poor pulmonary reserve may not be candiates for surgery.

Stage 3a (T3 N0 M0, T3 N1 M0 or T1-3 N2 Mo) These patients have locally advanced disease with hilar or ipsilateral mediastinal nodal metastasis, buta select few may be suitable for surgical resection. Prognosis is poor with 5 year survival less than 20 percent.

Stage 4 (T1-4 N1-3 M1) These patients have distant metastasis and have the worst overall prognosis. Surgery is of no proven benefit, but radiotherapy or chemotherapy may provide pallative relief. A Carney, Lung Cancer (Arnold Pub. Co., Great Britain, 1995)

 4.2 OCCULT NON-SMALL CELL LUNG CANCER (Stage 0)

TX, N0, M0

In occult lung cancer, a diagnostic evaluation often includes chest x-ray and selective bronchoscope with close follow-up (e.g., computed tomography scan), when needed, to define the site and nature of the primary tumor; tumors discovered in this fashion are generally early stage and curable by surgery. After discovery of the primary tumor, treatment is determined by establishing the stage of the patient's tumor. Therapy is identical to that recommended for other non-small cell lung cancer patients with similar stage disease.

Tis, N0, M0

Stage 0 non-small cell lung cancer (NSCLC) is the same as carcinoma in situ of the lung. Because these tumors are by definition noninvasive and incapable of metastasizing, they should be curable with surgical resection; however, there is a high incidence of second primary cancers, many of which are unresectable. Phototherapy has been described as an alternative to surgical resection in carefully selected patients. [1-3] This investigational treatment seems to be most effective for very early central tumors that extend less than 1 centimeter within the bronchus.[2] Efficacy of this treatment modality in the management of early NSCLC remains to be proven.

Treatment options:

1. Surgical resection using the least extensive technique possible (segmentectomy or wedge resection) to preserve maximum normal pulmonary tissue since these patients are at high risk for second lung cancers.

2. Endoscopic photodynamic therapy.[2,3]

Author's Note

A recent article discusses photodynamic therapy and its use with Stage 0 patients:

"Photodynamic therapy uses a photosensitiving agent, which becomes activated when exposed to light of the appropriate wavelength (1) and produces toxic oxygen radicals, resulting in cell death....Tissue penetrations is limited to a few millimeters in this method. This fact and the ralatively low power prohibit complete eradication of large obstructing airway lesions. However, successful eradication of superficial (penetration less than 5 millimeters) bronchial wall tumors has been demonstrated. Superficial tumors are usually squamous cell carcinomas that are radiographically occult. They are often detected through cytological examination of sputum.

Surgical resection remains the best treatment for early-stage lung cancer. However, photodynamic therapy may be considered for some operable cancers, for cancers that are inoperable because of high surgical risk or limited pulmonary function or because they are multicentric, and for cancer in patient who refuse surgery. To be a candidate for photodynamic therapy, a patients must have a superficial stage 1 lesion (i/e. no evidence of nodal metastasis) that has a surface area estimated to be less than 3cm."

Midthun, Endobrochial Techniques in Lung Cancer, Otpions for Nonsurgical Care. Vol. 101, No. 3, March 1997 Postgraduate Medicine

4.21 Description of Photdynamic Therapy

One hospital describes and touts its photodynamic therapy:

The Thompson Cancer Survival Center has announced the use of photodynamic therapy as a potentially curative treatment of early endobronchial lung cancer - cancer in the network of airways delivering air to the lungs. The Thompson Center is the first facility in Tennessee, and among only a few select cancer centers around the country, to offer this exciting treatment to its patients.

Photodynamic therapy, or PDT, uses a light-sensitive drug, called Photofrin, and laser light to kill cancer cells. The drug is injected into the patient and concentrates in tumors. Photofrin remains inactive until it is combined with a special laser light. The light activates the drug which produces a toxic form of oxygen that destroys tumor tissue.

For endobronchial lung tumors, the patient is injected with Photofrin. Two days later, laser light is delivered through a small optical fiber inserted through a bronchoscope, an instrument used for examination of the bronchial tubes. One to two days after the laser treatment, destroyed tumor tissue is removed during a second bronchoscopy procedure. The procedure is typically performed on an outpatient basis; however, an overnight hospital stay may be recommended for some patients.

According to Dr. Vijay Patil, the thoracic surgeon participating in this treatment, lung PDT offers several advantages over standard treatment. "The primary benefits of lung PDT are the limited side effects, preservation of the lung, and the fact that PDT can be repeated if necessary," said Dr. Patil. The doctor also notes a few limitations of the procedure. "Lung PDT is useful in patients with early-stage lung cancers in the bronchial tubes. Cancers that have advanced, even locally, cannot be treated with this procedure," said Dr. Patil.

Currently, photodynamic therapy is approved by the FDA for treatment of cancer of the esophagus and early lung cancer....

Lung photodynamic therapy is recommended as a potentially curative treatment for microinvasive endobronchial cancer in patients who are not good candidates for or have refused surgery or radiation. The primary side effect of PDT is light sensitivity. Photofrin stays in the skin for about four weeks, therefore, patients must avoid direct exposure to sunlight and bright lights during this time.www.covenanthealth.com Thompson Cancer Survival Center website

4.3 STAGE I NON-SMALL CELL LUNG CANCER

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

4.31 T1, N0, M0 or T2, N0, M0

Surgery is the treatment of choice for patients with stage I non-small cell lung cancer (NSCLC). Careful preoperative assessment of the patient's overall medical condition, especially the patient's pulmonary reserve, is critical in considering the benefits of surgery. The immediate postoperative mortality rate is age-related, but 3%-5% with lobectomy can be expected. Note that survival rates will vary, so choice of a surgeon and hospital can be important.

[1] Patients with impaired pulmonary function may be considered for segmental or wedge resection of the primary tumor; the Lung Cancer Study Group has conducted a randomized study (LCSG-821) to compare lobectomy with limited resection for patients with stage I cancer of the lung. The results of this study show a reduction in local recurrence for patients treated with lobectomy compared with those treated with limited excision but no significant difference in overall survival.[2] Similar results have been reported from a nonrandomized comparison of anatomic segmentectomy and lobectomy.[3] A survival advantage was noted with lobectomy for patients with tumors greater than 3 centimeters, but not for those with tumors smaller than 3 centimeters. However, the rate of local/regional recurrence was significantly less after lobectomy, regardless of primary tumor size. Another study of stage I patients showed that those treated with wedge or segment resections had a local recurrence rate of 50% (31 of 62) despite having undergone complete resections.[4] Exercise testing may aid in the selection of patients with impaired pulmonary function who can tolerate lung resection.[5] The availability of video-assisted thoracoscopic wedge resection permits limited resections in patients with poor pulmonary function who are not usually considered candidates for lobectomy.[6]

Patients with stage I disease for whom surgery is deemed inappropriate may be considered for radiation therapy with curative intent. In one report of patients older than 70 years of age who had resectable lesions smaller than 4 centimeters but who were medically inoperable or who refused surgery, survival at 5 years following radiation therapy with curative intent was comparable to a historical control group of patients of similar age resected with curative intent.[7] In the two largest retrospective radiation therapy series, inoperable patients treated with definitive radiation therapy achieved 5-year survival rates of 10% and 27%. Both series found that patients with T1, N0 tumors had better outcomes, with 5-year survival rates of 60% and 32% in this subgroup.[8,9]

Primary radiation therapy should consist of approximately 6,000 cGy delivered with megavoltage equipment to the midplane of the known tumor volume using conventional fractionation. A boost to the cone-down field of the primary tumor is frequently used to further enhance local control. Careful treatment planning with precise definition of target volume and avoidance of critical normal structures to the extent possible is needed for optimal results and requires the use of a simulator.

Many patients treated surgically subsequently develop regional or distant metastases.[10] Therefore, patients should be considered for entry into clinical trials evaluating adjuvant treatment with chemotherapy or radiation therapy following surgery. A meta-analysis of 9 randomized trials evaluating postoperative radiation versus surgery alone showed a 7% reduction in overall survival with adjuvant radiation in patients with stage I or II disease.[11][Level of evidence: 1iiA] It will be important to determine whether these outcomes can potentially be modified with technical improvements, better definitions of target volumes, and limitation of cardiac volume in the radiation portals. Trials of adjuvant chemotherapy regimens have failed to demonstrate a consistent benefit. Smokers who undergo complete resection of stage I NSCLC are also at risk for second malignant tumors. In the Lung Cancer Study Group trial of 907 stage T1, N0 resected patients, the rate of nonpulmonary second cancers was 1.8% per year and 1.6% per year for new lung cancers.[12] Others have reported even higher risks of second tumors in long-term survivors, including rates of 10% for second lung cancers and 20% for all second cancers.[4] A randomized trial of vitamin A versus observation in resected stage I patients showed a trend toward decreased second primary cancers in the vitamin A arm with no difference in overall survival rates.[13] An ongoing intergroup clinical trial will evaluate the role of isotretinoin in the chemoprevention of second cancers in patients resected for stage I NSCLC.[14]

Treatment options:

1. Lobectomy or segmental, wedge, or sleeve resection as appropriate.

2. Radiation therapy with curative intent (for potentially resectable patients who have medical contraindications to surgery).

3. Clinical trials of adjuvant chemotherapy following resection.[15,16]

4. Adjuvant chemoprevention trials.[13,14]

5. Endoscopic photodynamic therapy (under clinical evaluation in highly selected T1, N0, M0 patients).[17]

 

4.3 STAGE II NON-SMALL CELL LUNG CANCER

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

4.31 T1, N1, M0 or T2, N1, M0 or T3, N0, M0

Surgery is the treatment of choice for patients with stage II non-small cell lung cancer (NSCLC). Careful preoperative assessment of the patient's overall medical condition, especially the patient's pulmonary reserve, is critical in considering the benefits of surgery. The immediate postoperative mortality rate is age-related, but up to 5%-8% with pneumonectomy or 3%-5% with lobectomy can be expected.

Patients with stage II disease for whom surgery is not recommended but with sufficient pulmonary reserve may be considered for radiation therapy with curative intent.[1] Among patients with excellent performance status, up to a 20% 3-year survival rate may be expected if a course of radiation therapy with curative intent can be completed. In the largest retrospective series reported to date, 152 patients with medically inoperable NSCLC treated with definitive radiation therapy achieved a 5-year overall survival rate of 10%; however, the 44 patients with T1 tumors achieved an actuarial disease-free survival rate of 60%. This retrospective study also suggested that improved disease-free survival was obtained with radiation therapy doses greater than 6,000 cGy.[2] Primary radiation therapy should consist of approximately 6,000 cGy delivered with megavoltage equipment to the midplane of the volume of known tumor using conventional fractionation. A boost to the cone-down field of the primary tumor is frequently used to further enhance local control. Careful treatment planning with precise definition of target volume and avoidance of critical normal structures to the extent possible is needed for optimal results and requires the use of a simulator.

Many patients treated surgically subsequently develop regional or distant metastases.[3] Therefore, patients should be considered for entry into clinical trials evaluating the use of adjuvant treatment with chemotherapy or radiation therapy following surgery. One controlled trial has failed to demonstrate an overall survival benefit for patients with carefully staged squamous cell carcinoma receiving postoperative irradiation, although local recurrences were significantly reduced.[4] A meta-analysis of 9 randomized trials evaluating postoperative radiation versus surgery alone showed a 7% reduction in overall survival with adjuvant radiation in patients with stage I or II disease.[5][Level of evidence: 1iiA] It will be important to determine whether these outcomes can potentially be modified with technical improvements, better definitions of target volumes, and limitation of cardiac volume in the radiation portals. In two controlled trials in carefully staged, surgically resected patients, adjuvant combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide produced modestly increased disease-free survival and a trend toward improved overall survival, especially in the first year after surgery.[6,7] Based on these data, participation in clinical trials evaluating adjuvant therapy after surgical resection should be encouraged.

Treatment options:

1. Lobectomy, pneumonectomy, or segmental, wedge, or sleeve resection as appropriate.

2. Radiation therapy with curative intent (for potentially operable patients who have medical contraindications to surgery).

3. Clinical trials of adjuvant chemotherapy with or without other modalities following curative surgery.[6-8]

4. Clinical trials of radiation therapy following curative surgery.[8]

To preserve space, footnotes are omitted, to review footnotes for chapter 4, go to.  Chapter 4 References, non-small cell lung cancer

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EXCERPTS FROM A COMPLETE GUIDE TO LUNG CANCER S

Chapter 1-2   cancer overview How cancer develops, staging, different types of lung cancer, difference between non-small cell and small cell

Chapter 4 
    Non-small cell lung cancer   Non-Small Cell treatment categorized by stage, chemotherapy, radiation,  

Chapter 5     smallcelllungcancer Small Cell treatment and overview 

Chapter 6      Chemotherapy (What is chemotherapy, different types of drugs, cisplatin, clinical trial results, new developements).

Chapter 9       Lung Cancer Surgery (Types of lung cancer surgery)

Chapter 11       Lung Cancer clinical trial overview 

Chapter 17     HMO.htm  HMO problems and medical insurance issues.

                   Tumor stages ) Explanation of the TNM (Tumor, Node, Metastais) staging system for non small cell lung cancer. 

Lung Cancer Newsletter Lung Cancer Newsletter   The Lung Cancer Newsletter is a detailed newsletter published at least three times per year of about 20-25 pages per issue devoted to recent developments in treatment and diagnosis of lung cancer.  Clinical studies, research reports, and articles in major medical journals are reviewed and summarized.  Learn about the latest medical research, treatments, clinical trials, and developments in chemotherapy.  Order the Lung Cancer Newsletter for $95.00 and receive a complimentary copy of our book.  The newsletter is offered with a money-back guarantee. 

Authored by Howard A. Gutman, as part of A Complete Guide to Lung Cancer
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