THE LUNG CANCER NEWSLETTER

The Lung Cancer Newsletter is a publication devoted to recent developments in lung cancer treatment and diagnosis.  Published at least 3 times per year in issues of 20-25 pages, the newsletter surveys developments in over 100 medical journals, excerpting significant findings and trends in cancer treatment, chemotherapy, cancer etiology, clinical trials, and more.  The opening issue is set forth below.  

LUNG CANCER DEVELOPMENTS

I. DETERMINANTS OF LONG TERM SURVIVAL

Five year survival for patients with tumors surgically removed likely means long term survival. Other factors found to be irrelevant.

An article in the Journal of Thoracic Medicine studied survival patterns of surgically treated lung cancer patients at Sloan Kettering Hospital, (ranked the second best hospital in the nation in the recent U.S News and World Report study). The study abstract states, AIn patients with surgically treated lung cancer, neither age, sex, histological condition, nor stage is a predictor of the risk of late recurrence or new lung cancer. The only prognostic factor appears to be the survival of the patient free of lung cancer for 5 years from the initial treatment, with a resultant favorable outlook to remain well for 10 or more years.

Editor's Comment, The study results are somewhat surprising. Based on prior studies, one would expect a strong correlation between stage and survival, as other studies have found. The authors studied patients who had been surgically treated and survived ten years, but were not able to identify particular characteristics in that group. If overall patterns of survival had been examined, as opposed to simply looking at the group with excellent results, one would expect to see a close correlation between stage and survival rates as many have reported.

The results should give comfort and hope for those patients who can be surgically treated, but whose cancers may be somewhat advanced as in a stage 2 or stage 3A cancer. In the survival group, stage 2 and 3 patients generally did as well as stage 1 patients. Certainly people in that group have a realistic possibility of long-term survival. The study should give those considering experimental therapy some thought, since at least some excellent results were achieved with conventional treatment at a well-regarded hospital. Don't give up is perhaps the lesson.

Title, Factors influencing ten-year survival in resected stages I to IIIa non-small cell lung cancer.Authors, Martini N; Rusch VW; Bains MS; Kris MG; Downey RJ; Flehinger BJ;
 

Ginsberg RJ Address Thoracic Division, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Source J Thorac Cardiovasc Surg, 1999 Jan, 117:1, 32-6; discussion 37-8

B. PATTERNS OF CANCER INCIDENCE

Study examines characteristics of under 50 cancer victims. Percentage of women in this group increases along with percentage of adenocarcinomas.

A long-term retrospective study was carried out on 790 cases of lung cancer to determine if the clinicopathologic characteristics and survival rates of lung cancer patients under the age of 50 differ from those of patients 50 years of age or older at diagnosis by analyzing data on patients registered at Tochigi Cancer Center Hospital. Of the 790 patients, 77 (9.7%) were under the age of 50 at diagnosis. The percentage of women in the younger patient group was significantly higher than that in the older patient group (39.0% vs. 27.5%; P = 0.034). Tumor histology revealed a significant preponderance of adenocarcinomas (60 patients, 77.9%) and a paucity of squamous cell carcinomas (8 patients, 10.4%) in the younger age group.

Title Lung cancer in patients under 50 years old. Author Tominaga K; Mori K; Yokoi K; Noda M; Goto N; Machida S; Nagai M Source Jpn J Cancer Res, 1999 May, 90:5, 490-5

II. CAUSES OF LUNG CANCER

A. RADON

Link between radon and lung cancer seen in study of Missouri Women

Missouri women (aged 30 to 84 years) newly diagnosed with primary lung cancer during the period January 1, 1993, to January 31, 1994, were invited to participate in this population-based case-control study. Both indoor air radon detectors and CR-39 alpha-particle detectors (surface monitors) were used. RESULTS: When surface monitors were used, a significant trend in lung cancer odds ratios was observed for 20-year time-weighted-average radon concentrations. CONCLUSIONS: When surface monitors were used, but not when standard radon dosimetry was used, a significant lung cancer risk was found for radon concentrations at and above the

action level for mitigation of houses currently used in the United States (148 Bqm-3). The risk was below the action level used in Canada (750 Bqm-3) and many European countries (200-400 Bqm-3).

Title Residential radon exposure and risk of lung cancer in Missouri.

Author Alavanja MC; Lubin JH; Mahaffey JA; Brownson RC

Address Division of Cancer Epidemiology and Genetics, National Cancer

Institute, Bethesda, Md. 20892, USA.

Source Am J Public Health, 1999 Jul, 89:7, 1042-8

B. Genetic Factors

Genetic weakness in repairing DNA damage due to smoking contributory factor in developement of lung cancer.

The abstract states,

The major risk factor for lung cancer is exposure to tobacco smoke. Exposure to radon, heavy metals used in smelting, and asbestos also greatly increase risks for lung cancer. However, only about 11% of tobacco smokers ultimately develop lung cancer, suggesting that genetic factors may influence the risk for lung cancer among those who are exposed to carcinogens. Further support for this hypothesis is provided by several epidemiological studies and also from molecular epidemiological studies. Epidemiological studies show approximately 14-fold increased risks for lung cancer among average tobacco smokers and approximately 2.5-fold increased risks attributable to a family history of lung cancer after controlling for tobacco smoke. Segregation analyses suggest that a rare autosomal dominant gene may explain susceptibility to early-onset lung cancer, but these results explain a minority of lung cancer cases, which include a family history. Therefore, more common genetic variants or polymorphisms are hypothesized to affect lung cancer risk. Environmental carcinogenesis resulting from tobacco smoke exposure is a complex process that can involve activation of procarcinogens that lead to adduct formation and subsequent failure of DNA repair, which should normally remove these adducts. Studies comparing DNA repair capacity among newly diagnosed lung cancer patients and age-matched controls indicate significant differences between the two groups....

Results from this assay show an even more significantly higher level of damaged chromatids in lung cancer patients than in controls. Poor DNA repair is independent of tobacco smoking status. The cellular processes involved in DNA repair of bleomycin and BPDE have not yet been fully elaborated. However, the consistency of findings with these two carcinogens indicates that DNA repair capacity influences risk for lung cancer among individuals.

Title

Is there a genetic basis for lung cancer susceptibility?

Author

Amos CI; Xu W; Spitz MR

Source

Recent Results Cancer Res, 1999, 151:, 3-12

IV. TREATMENT OF BRAIN CANCER (BRAIN METASTASIS)

A. USA Today Reports Favorable Results Using Thalidomide to Treat Brain Cancer

The August 24, 1999 issue of USA today reports that 50% of patients with glioblastoma, an aggresive form of brain cancer responded favorably to Thaldiomide. Thalidomine was banned in throughout the world after it caused birth defects when taken by pregnant women. However, the characteristic of the drug which contributed to this may also help reduce the spread of cancer. The Thalidomide had the result of cutting off each cancer blood supply. Thalidomide is a Aangiogenesis inhibitor,@ a drug which attacks cancer by cutting off the blood supply that a cancer requires to grow. However, the drug should not be viewed as a cure, while the use of the drug seemed to extend life, the cancer recurred in the 50% of the patients who had favorable initial responses. For additional information, contact the Angiogenesis Foundation, 617, 576-5708.

B. New England Journal of Medicine Study finds beneficial results in prophylactic cranial irradiation for small-Cell Lung Cancer

Small-cell lung cancer accounts for 20 to 25 percent of all cases of lung cancer (approximately 45,000 new cases per year in the United States). Limited disease (disease confined to the lung) accounts for 30 to 40 percent of all newly diagnosed cases of small-cell lung cancer. It is treated with combination chemotherapy and thoracic irradiation of the site of the primary tumor. With this approach, the median survival is 18 months, and up to 25 percent of patients survive for more than 2 years. The article states,

AA major cause of morbidity and mortality in patients with small-cell lung cancer is brain metastasis, which in most patients results in multiple tumors. At the time of initial diagnosis, brain metastases can be detected in up to 10 percent of patients, and 1 to 2 percent of these patients have metastases only in the brain. However, among patients who complete chemotherapy, an additional 30 to 70 percent subsequently have clinically apparent brain metastases, and even more have such metastases at autopsy. (5) Moreover, among patients who have a complete remission with chemotherapy, approximately 15 percent have brain metastases as the initial or sole manifestation of recurrence. As the length of survival after diagnosis increases, the risk of metastases to the brain increases. Thus, as chemotherapy with concurrent thoracic irradiation becomes more effective for patients with limited small-cell lung cancer, the frequency of brain metastases later in the course of the disease may continue to rise.

For many years, prophylactic cranial irradiation has been used in patients with small-cell lung cancer in the belief that the treatment of microscopic or subclinical metastases would prevent or delay the onset of symptomatic brain metastases, but its efficacy for this purpose has been uncertain. Those who advocate prophylactic cranial irradiation point out that it is a safe way to reduce the overall incidence of brain metastases, even if only a small number of patients benefit. (6,7) Others argue against routine prophylactic cranial irradiation. They point out that the brain is rarely the sole site of recurrence, that radiation can be neurotoxic, and that radiation therapy does not prolong survival. (8,9)

In this issue of the Journal, Auperin et al. report the results of a detailed meta-analysis of the efficacy of prophylactic cranial irradiation in 987 patients (847 patients with limited disease and 140 patients with extensive disease) who took part in seven trials and who had complete remission with chemotherapy, with or without thoracic irradiation. (10) Prophylactic cranial irradiation was associated with an absolute decrease of 25.3 percent in the cumulative incidence of brain metastasis at three years, from 58.6 percent in the control group to 33.3 percent in the treatment group. More important, prophylactic cranial irradiation was also associated with an absolute increase in overall survival of 5.4 percent at three years, from 15.3 percent in the control group to 20.7 percent in the treatment group. Prophylactic cranial irradiation was beneficial in patients with either limited or extensive disease. As previously reported in the two largest trials included in the meta-analysis, in which neuropsychological tests were performed on most but not all patients before, during, and after treatment, neurocognitive impairment was often detected at diagnosis, but no deterioration was found after prophylactic cranial irradiation. (6,7)

This study confirms that there is a small absolute survival advantage for patients who receive prophylactic cranial irradiation. Even though this advantage is small, it is important: early studies of thoracic irradiation in patients with limited-stage small-cell lung cancer revealed no significant trend toward improved survival, but when large numbers of patients were studied, the small absolute survival benefit associated with thoracic irradiation was identified. (2,3) Today, for almost all patients with limited small-cell lung cancer, thoracic irradiation is an integral part of therapy.

We still do not know how best to integrate prophylactic cranial irradiation with chemotherapy in patients with small-cell lung cancer. The optimal dose of radiation, volume of tissue to be irradiated, and duration and timing of prophylactic cranial irradiation have not been determined. Also, questions remain regarding the safety and long-term neuropsychological consequences of prophylactic cranial irradiation. The study found a significant survival benefit, but it should be noted that four of the trials included in the meta-analysis had fewer than 100 patients, which suggests that there may have been some selection bias.

On the basis of the data presented, it is now reasonable to include prophylactic cranial irradiation as part of the treatment of patients with limited small-cell lung cancer who are in complete remission (usually evident after three or four cycles of chemotherapy) and of patients with extensive disease who have isolated metastases and are in complete remission. To minimize the risk of neurologic damage, prophylactic cranial irradiation should not be administered concurrently with chemotherapy or to elderly patients. As treatment of the primary tumor in patients with small-cell lung cancer improves, brain metastases are likely to become an increasingly frequent manifestation of treatment failure. Thus, studies are needed to define the optimal dose and fractionation schedule for prophylactic cranial irradiation and to determine how best to integrate this therapy with chemotherapy and thoracic irradiation.   

RELATED LINKS

For excerpts from The Complete Guide to Lung Cancer, go to lungcancerbook.htm. The book begins by generally describing cancer and its causes, reviews lung anatomy, and then discusses treatment alternatives at different stages.  Excerpts include discussion of lung cancer staging systems, non-small cell and small cell cancers, types of surgery, survival rates, chemotherapy and radiation, other treatments, different types of surgery, smoking and cancer, organizations involved with lung cancer. Go to the entire book site or individual topics as follows

            Chapter 1-2  lungcanceroverview how cancer develops,        staging, different types of lung cancer, difference between                   non-small cell and small cell lung cancer from A Complete Guide to Lung Cancer)

            Chapter 4    
nonsmallcelllungcancer.htm Non-Small Cell lung cancer, treatment categorized by stage, chemotherapy,                       radiation, prognosis categorized by stage,

            Chapter 5 
  smallcelllungcancer.htm (Small Cell lung cancer, 
staging, metastasis, from A Complete Guide to Lung Cancer)

                            lungcancerstages.htm    (lung cancer stages, pathology, categories, general overview, not part of the book).

Legal Issues

To learn about lung cancer victims rights to compensation, go to
                                                    compensationforlungcancer.htm
(Note, Exposure to dangerous dusts in the workplace is the second leading cause of lung cancer. Approximately 25% of lung cancer victims will be entitled to compensation based upon their workplace exposures, but relatively few will actually file claims.)

For information about medical malpractice claims based upon the failure to timely diagnose lung cancer, go to   failuretodiagnosecancer.htm

Profile

Howard Gutman is a New Jersey attorney based in Parsippany, New Jersey who has handled numerous legal claims involving lung cancer.   A member of a leading cancer support group, he has been an advocate for early lung cancer detection programs and is the author of the upcoming book, A Complete Guide to Lung Cancer.

Mr. Gutman clerked at a Wall Street law firm, and was employed by a large New Jersey firm before establishing his own legal practice. His cases have include lung cancer, mesothelioma, silicosis, asbestos, and sarcoidosis.    He has also appeared on Good Day New York and been interviewed by NBC Nightly News.

Contact Information

Telephone
 
Howard A. Gutman, ]973-257-9400 (all consultations are without charge)
FAX
973-257-9128
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Electronic mail
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Occasionally you may have difficulty with e-mail. Please feel free to call our office with any questions, or comment, and there is no charge for such calls, and we welcome your input.

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