Late stage (III and IV) non-small cell cancer of the lung: results of surgical resection at Inova Fairfax Hospital.Abstract: One hundred forty-two patients underwent surgery and related treatment for advanced stage (III, IV) non-small cell cancer of the lung. One hundred seventeen patients underwent up-front surgery, with a hospital mortality rate of 1.7% (2/117). Kaplan-Meier 5-year survival in this group was 31% ([+ or -] 5). Twenty-five patients underwent neoadjuvant therapy Neoadjuvant therapy
Radiation therapy or chemotherapy used to shrink a tumor before surgical removal of the tumor.
Mentioned in: Thymoma
neoadjuvant therapy 1 Neoadjuvant chemotherapy, see there 2. followed by surgical resection, with respective rates of hospital mortality, complete pathologic response, and major pathologic response of 0%, 16%, and 64%. Kaplan-Meier 5-year survival in this latter group was 34% ([+ or -] 11). Of the 16 patients undergoing neoadjuvant therapy who had complete pathologic response or significant downstaging from stage III disease, Kaplan-Meier 5-year survival was 61% ([+ or -] 15). Three clinical observations of interest emerged regarding survival. First, in those patients with postresection FE[V.sub.1] < 1.0 L, hospital mortality rate was 20%, and there were no 5-year survivors (P < 0.0001). Second, where neoadjuvant therapy was associated with complete pathologic response or significant downstaging of disease, there was a trend for improved survival in the downstaged group, but it did not reach statistical significance (P = 0.14). Third, adjuvant therapy Adjuvant therapy
A treatment done when there is no evidence of residual cancer in order to aid the primary treatment. Adjuvant treatments for endometrial cancer are radiation therapy, chemotherapy, and hormone therapy. was associated with improved 5-year survival (P = 0.03), particularly for combination chemotherapy and radiotherapy (P = 0.02).
Key Words: lung cancer, non-small cell Lung Cancer, Non-Small Cell Definition
Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.
There are two kinds of lung cancers, primary and secondary. , late stage, neoadjuvant therapy, adjuvant therapy
Carcinoma of the lung is the single leading cause of death from cancer in men and women, responsible for greater than one quarter of all such deaths. (1) Many studies (2-4) attest to the benefit of surgical resection of non-small cell carcinoma of the lung (NSCCL NSCCL Non-Small Cell Carcinoma of the Lung
NSCCL NSE National Securities Clearing Corporation Limited ), when diagnosed in advance of metastases Metastasis (plural, metastases)
A tumor growth or deposit that has spread via lymph or blood to an area of the body remote from the primary tumor.
Mentioned in: Malignant Melanoma to mediastinal mediastinal /me·di·as·ti·nal/ (-as-ti´n'l) of or pertaining to the mediastinum.
of or pertaining to the mediastinum. lymphatics Lymphatics
Channels that are conduits for lymph.
Mentioned in: Colon Cancer, Rectal Cancer (stage III-A) or even more advanced (stage III-B and IV) disease. Until quite recently, with few exceptions, (5-8) surgical treatment for advanced disease was considered only palliative palliative /pal·li·a·tive/ (pal´e-a?tiv) affording relief; also, a drug that so acts.
Relieving or soothing the symptoms of a disease or disorder without effecting a cure. and the end results dismal. (3,6,9) More recently, we (10) and others (11-14) have reported surgical series of advanced stage NSCCL with significant improvements over historic reports for both hospital mortality and long-term survival.
Between January 1, 1991, and October 31, 2003, 666 patients underwent complete surgical resection for NSCCL at Inova Fairfax Hospital Inova Fairfax Hospital is the largest hospital in the Washington D.C. area. Located in Fairfax County, Virginia, Inova Fairfax Hospital is the flagship hospital of Inova Health System, one of the largest employers in Fairfax County. . Of that group, 24% (163/666) had advanced late stage (III, IV) disease. Although prior studies have reported much poorer long-term survival, (3,6,9) our experience in this group (10) was so encouraging that we decided to examine in more detail our patients with advanced late stage disease.
Materials and Methods
Of the original 163 patients who had advanced-stage disease and good-to-excellent performance status, 21 patients were eliminated for this review. Nine patients were eliminated because the differentiation of N2 from N1 lymph node lymph node
Small, rounded mass of lymphoid tissue contained in connective tissue. They occur all along lymphatic vessels, with clusters in certain areas (e.g., neck, groin, armpits). might reasonably be questioned; level 10 was classified as an N1 lymph node. (15) Six patients with neuroendocrine neuroendocrine /neu·ro·en·do·crine/ (-en´do-krin) pertaining to neural and endocrine influence, and particularly to the interaction between the nervous and endocrine systems.
adj. histology histology (hĭstŏl`əjē), study of the groups of specialized cells called tissues that are found in most multicellular plants and animals. were eliminated to remove any doubts as to whether survival benefit accrued from possible inadvertent inclusion of carcinoid-type tumors. Four patients were eliminated because a definitive histology was not possible--two of whom underwent needle biopsy needle biopsy
Removal of a specimen for biopsy by aspirating it through a needle or trocar that pierces the skin or the external surface of an organ and continues into the underlying tissue to be examined. Also called aspiration biopsy. elsewhere. Finally, two patients were eliminated when a previous staging classification of stage III (T3N0) was carried over inadvertently as stage III in the newer lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell. classification. (16)
All of the remaining 142 patients underwent complete surgical resection of stage III or IV NSCCL, as detailed by clinical and pathologic staging according to according to
1. As stated or indicated by; on the authority of: according to historians.
2. In keeping with: according to instructions.
3. the New International Staging System Staging system
A system based on how far the cancer has spread from its original site, developed to help the physician determine how best to treat the disease.
Mentioned in: Neuroblastoma for Lung Cancer, (16,17) as accepted by the American Joint Committee on Cancer The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards. External links
Small, bean-shaped masses of tissue scattered along the lymphatic system that act as filters and immune monitors, removing fluids, bacteria, or cancer cells that travel through the lymph system. were removed, even if the most distal node was found to be involved." (6) Final staging was based on total histologic review of resected lung, lymph nodes, and tissues.
No single regimen of preoperative pre·op·er·a·tive
Preceding a surgical operation.
preceding an operation.
the preparation of a patient before operation. (neoadjuvant) chemotherapy was followed. Multiple oncology groups used a variety of cis/carboplatin regimens, with varying number of cycles and supplemental agents. Neoadjuvant radiation ranged from 4,500 to 6,300 Gray (Gy), most commonly 4,500 to 5,000 Gy. For postoperative (adjuvant adjuvant /ad·ju·vant/ (aj?dbobr-vant) (a-joo´vant)
1. assisting or aiding.
2. a substance that aids another, such as an auxiliary remedy.
3. ) care, the style and degree of chemotherapy and radiotherapy also varied considerably.
Patient survival was examined by age, sex, cell type, TNM classification TNM classification Oncology An international system for staging malignancy which measures 3 major parameters of a cancer: T–size or extent of the primary tumor, as determined by clinical exam, endoscopy, laparoscopy, biopsy or resective procedures, , type of therapy, and extents of tumor and resection. Hospital mortality rate was also calculated. Information with regard to lymph node staging was obtained from tissue submitted for pathology review, whether from resected pulmonary parenchyma Parenchyma
A ground tissue of plants chiefly concerned with the manufacture and storage of food. The primary functions of plants, such as photosynthesis, assimilation, respiration, storage, secretion, and excretion—those associated with living and nodes obtained at thoracotomy thoracotomy /tho·ra·cot·o·my/ (-kot´ah-me) pleurotomy; incision of the chest wall.
Incision into the chest wall. Also called pleurotomy. , from prethoracotomy surgical staging procedures, or both.
Follow-up in this cohort was 100%, and the censor date for those patients still alive was October 31, 2003. Survival was calculated according to the method of Kaplan-Meier, (19) and the log-rank test was used to compare two or more survival curves. (20) Statistical significance was defined as P [less than or equal to] 0.05. Also, simple alive/dead proportions were calculated, irrespective of irrespective of
Without consideration of; regardless of.
preposition despite staging, therapy or cause of death.
Of the 142 patients, 56% were male (80/142) and 44% (62/142) were female. Patient ages ranged from 32 to 82 years and did not differ significantly by gender. Preoperative estimates of postoperative 1-second forced expiratory volumes forced expiratory volume
n. Abbr. FEV
The maximum volume of air that can be expired from the lungs in a specific time interval when starting from maximum inspiration. (FE[V.sub.1]) in these patients were characterized as <1.0 L, [greater than or equal to]1.0 L, and unknown. The corresponding proportions of patients falling into these categories were 7% (10/142), 80% (113/142), and 13% (19/142). Tumors were classified according to histology, stage, and TNM TNM tumor-nodes-metastasis; see under staging.
tumor, nodes and metastases; a system of cancer staging (see TNM staging). subgroups. With regard to cell type, 58% (83/142) of these patients had squamous cell squamous cell
A flat, scalelike epithelial cell. tumors, whereas 37% (53/142) had adenocarcinomas and 4% (6/142) had large cell undifferentiated carcinomas.
With regard to final stage of disease, 16 patients were downstaged by neoadjuvant therapy to stage 0 or complete pathologic response (CPR Cardiopulmonary Resuscitation (CPR) Definition
Cardiopulmonary resuscitation (CPR) is a procedure to support and maintain breathing and circulation for a person who has stopped breathing (respiratory arrest) and/or whose heart has stopped (cardiac ) (4 patients), I-A (3 patients), I-B (4 patients), and II-B (5 patients). Seventy-one patients were classified as stage III-A and 40 patients as stage III-B. Fifteen patients were stage IV, either resected of multiple cancers in one lobe with concomitant nodal Having to do with nodes. See node.
NODAL - Interpreted language implemented on Norsk Data's NORD-10 computers. Used by CERN and DESY high energy physics labs to control their accelerator hardware, PADAC and SEDAC. Included trackball input, graphics. metastases or of separate cancers in different lobes at the same operation. Finally, 49 of 68 patients with N2 disease harbored single-level mediastinal metastases, whereas 12 patients harbored multiple-level metastases and 7 harbored indeterminate metastases.
[FIGURE 1 OMITTED]
Diagnostics and therapeutics
All patients in this series underwent complete surgical resection according to Watanabe criteria. (6) All patients treated neoadjuvantly completed their preoperative therapy before undergoing resection. Follow-up in these patients was 100%, encompassing all groups and subgroups. Eighty-two percent (117/142) of these patients underwent up-front surgical resection, 31% of these (36/117) with mediastinoscopy/mediastinotomy. Also in this up-front surgical resection group, 26% (30/117) underwent positron emission tomography positron emission tomography: see PET scan.
positron emission tomography (PET)
Imaging technique used in diagnosis and biomedical research. (PET) and 100% underwent CT.
Of the total group, 18% (25/142) underwent preoperative (neoadjuvant) therapy. Sixteen patients received chemotherapy and 9 patients received chemotherapy plus radiotherapy before undergoing surgical resection. All 25 patients underwent preoperative CT scanning CT scanning
Computer tomography scanning is a diagnostic imaging tool that uses x rays sent through the body at different angles.
Mentioned in: Apraxia . Of the 16 patients pretreated with chemotherapy, downstaging occurred in 63% (10/16). Thirteen of the 16 tested positive either for hypermetabolic mediastinum mediastinum /me·di·as·ti·num/ (me?de-ah-sti´num) pl. mediasti´na [L.]
1. a median septum or partition.
2. on PET (10 patients) and/or with positive nodal pathology at mediastinoscopy/mediastinotomy (6 patients). Of the remaining 3 patients, 1 underwent negative mediastinoscopy, emerging stage III-A (T3N1) after neoadjuvant therapy and subsequent resection. The final two patients were treated on the basis of CT alone, emerging after therapy with III-B and I-B disease. The patient with stage 1-B disease died 2 months after surgery.
In 10 instances in which mediastinoscopy/mediastinotomy was negative or not performed in the face of hypermetabolic (positive) mediastinum on PET, PET was repeated before surgery but after chemotherapy in four patients. Two of the four repeat PET scans were negative and two PET scans remained positive. The two latter patients were resected of I-B and II-B disease and, at postoperative follow-up, both patients remained alive, the former at 13 months and the latter at 16 months. Of the remaining 6 patients, 3 were resected of stage III disease. Two of these remained alive at 60 and 30 months, respectively, and one died at 15 months after surgery. The final three were resected of stage 0, 0 and II-B disease. Two remained alive at 49 and 43 months, respectively, and one died at 2 months after surgery. In the above 6 patients, no granulomatous granulomatous /gran·u·lom·a·tous/ (-lom´ah-tus) containing granulomas.
Resembling a tumor made of granular material. changes or any other explanation for the mediastinally positive PET scans were found.
Of the 9 patients treated neoadjuvantly with chemotherapy plus radiotherapy, downstaging occurred in 67% (6/9). Eight patients tested positive with either hypermetabolic mediastinum on PET scan (6 patients) and/or with nodal pathology at mediastinoscopy/mediastinotomy (4 patients). The remaining patient was resected of stage III (T2N2) disease. In all four instances in which mediastinoscopy/mediastinotomy was negative or not performed in the face of hypermetabolic (positive) mediastinum on PET, PET was repeated before surgery but after chemotherapy and radiotherapy. All four repeat PET scans were negative. The mediastinal nodes were negative in all four at surgery, with three patients staged II-B and one staged I-B.
Lobectomy lobectomy /lo·bec·to·my/ (lo-bek´tah-me) excision of a lobe, as of the lung, brain, or liver.
Excision of a lobe of an organ or a gland. was the most commonly performed lung resection technique, involving 96 patients, of whom 7 underwent bilobectomy and 1 sleeve lobectomy. Pneumonectomy pneumonectomy /pneu·mo·nec·to·my/ (-nek´tah-me) excision of lung tissue; it may be total, partial, or of a single lobe (lobectomy) .
pneu·mo·nec·to·my or pneu·mec·to·my
n. was performed in 29 patients (13 right, 16 left). Wedge resection wedge resection
Surgical removal of a wedge-shaped portion of tissue, as of the ovary.
wedge resection A triangular piece of tissue removed in surgery, most commonly obtained in 2 distinct contexts Gynecology A was performed in 17 patients. Resection of a portion of the chest wall or mediastinum was also performed in 15 and 4 patients, respectively.
Hospital mortality rate was 1.4% (2/142). Both deaths occurred after performance of right pneumonectomy, and both occurred in the group of 10 patients whose preoperatively calculated postoperative FE[V.sub.1] was less than 1.0 L. There were no statistically significant differences in 5-year survival patterns among patients examined by extent of resection: pneumonectomy versus lobectomy versus wedge resection (P = 0.49). The single most significant factor in early and late patient death was predicted, postoperative FE[V.sub.1] (P < 0.0001, Table 2).
No statistically significant differences in 5-year survival were found between the 117 patients undergoing up-front surgical resection and the 25 patients treated neoadjuvantly (P = 0.73, Table 3-A). No statistically significant survival differences were found between neoadjuvant chemotherapy Neoadjuvant chemotherapy
Treatment of the tumor with drugs before surgery to reduce the size of the tumor.
Mentioned in: Neuroblastoma
neoadjuvant chemotherapy and neoadjuvant chemotherapy plus radiotherapy (P = 0.19, Table 3-B). The lack of a statistically significant difference here may be due to small sample size and insufficient accrual survival time in the neoadjuvant chemotherapy plus radiotherapy group to permit a 5-year comparison. Finally, no statistically significant differences in survival were found between neoadjuvant chemotherapy plus surgery and up-front surgery (P = 0.32, Table 3-C1). Again, the limited sample of patients treated neoadjuvantly with chemotherapy plus surgery may be an issue here.
Sixteen patients were treated with preoperative (neoadjuvant) chemotherapy before undergoing surgical resection. Six of these patients had N2 disease that was not pathologically proven, either before or after surgery. At follow-up, 1 patient with stage 0 disease died at 2 months, 1 patient with stage I-B disease died at 2 months, 1 patient with stage 0 was alive at 49 months, 1 patient with stage I-B disease was alive at 13 months, and 2 patients with stage II-B disease were alive at 16 and 43 months, respectively. To examine whether the inclusion of these six patients might create an unintended bias toward longer survival, we eliminated them from the neoadjuvant chemotherapy plus surgery group. We then compared the remaining 10 patients with the 117 patients in the up-front surgery group (Table 3-C2) and found no statistically significant differences in survival (P = 0.41). Again, the limited sample of patients treated neoadjuvantly with chemotherapy plus surgery may be an issue here.
Table 4 depicts the survival experience of our stage III/IV patients. Of the 25 patients who were treated neoadjuvantly, 64% (16/25) were postoperatively downstaged to one degree or another. Five-year survival five-year survival Epidemiology The timespan that a person survives with a particular dread disease, in particular CA; 5YS facilitates standardization of survival statistics. See Cancer-free survival. in the downstaged group was 61% versus 25% in the group with N2 disease, although this difference was not statistically significant (P = 0.14). Although patients with single-level N2 disease appeared to have 5-year survival rates superior to those with multilevel mul·ti·lev·el
Having several levels: a multilevel parking garage.
Adj. 1. multilevel - of a building having more than one level disease (34% versus 16%), there was no statistically significant difference (P = 0.19).
Finally, Table 5 depicts the survival experience of patients by postoperative (adjuvant) therapy. Patients treated adjuvantly with chemotherapy with or without radiation showed the best survival (P = 0.02).
This review of our survival experience in stages III and IV NSCCL has several limitations. First, the review is retrospective. Second, although we are able to distinguish single-level N2 disease from multilevel N2 disease, (12,14) we did not differentiate between complete and incomplete resection on the basis of Mountain's lymphatic lymphatic /lym·phat·ic/ (lim-fat´ik)
1. pertaining to lymph or to a lymphatic vessel.
2. a lymphatic vessel.
adj. criteria. (21) Third, not all N2 disease was pathologically proven before surgery. Fourth, different and varying regimens of chemotherapy and radio-therapy were used in the neoadjuvant and adjuvant groups. Nevertheless, the 5-year survival achieved with an aggressive surgical strategy was 31%, at minimum.
Although the latter are Kaplan-Meier estimates, not actuarial survivals as recently reported by Machtay, (11) our survivals with surgery up front would seem at first glance to equal that achieved at the University of Pennsylvania (body, education) University of Pennsylvania - The home of ENIAC and Machiavelli.
Address: Philadelphia, PA, USA. (11) with radiotherapy to 45 to 54 Gy and concurrent chemotherapy. Clearly, such is not the case, as it has long been known that extended survivals and cures may be achieved when operating on and resecting occult, mediastinal (N2) disease. (3,5,7,8) We also have continued Martini's (22) lead into neoadjuvant application of chemotherapy plus or minus radiotherapy before operating for advanced disease. Just as the University of Pennsylvania (11) celebrates improved 5-year survival to 48% with major pathologic response, we also note improvement to 61% in 5-year survival in that group downstaged by neoadjuvant therapy (refer to Table 4, "downstaged"). As fully 64% of our neoadjuvantly treated patients are downstaged significantly, application of neoadjuvant therapy to aggressive surgical resection is increasingly seen to bear improved results. (11,22)
Compared with the results of Machtay et al, (11) our results using single-agent, neoadjuvant chemotherapy improved CPR by 46% (19% versus 13%) and overall major pathologic response by 50% (63% versus 42%), and our hospital mortality rate of 0% in this group compares favorably with their "early death rate of 9%." Even if the six patients not histologically proven before surgery to harbor stage III disease were deleted from the neoadjuvant chemotherapy group, the remaining 10 patients had respective hospital mortality rates, CPR, major pathologic response, and 5-year survival rates of 0%, 10%, 40%, and 39%. In view of these results and those of Memorial Sloan-Kettering, (23) in which "the addition of (preoperative) radiotherapy did not significantly increase survival," we continue to favor simple but aggressive neoadjuvant chemotherapy alone for patients with bulky mediastinal disease whose clinical performance status is good to excellent.
Given the benefits and limitations of neoadjuvant therapy, we do not subscribe to Verb 1. subscribe to - receive or obtain regularly; "We take the Times every day"
buy, purchase - obtain by purchase; acquire by means of a financial transaction; "The family purchased a new car"; "The conglomerate acquired a new company"; a forced choice of either neoadjuvant or adjuvant therapy. If patients are deemed fit enough, we will aggressively pursue a triple regimen (neoadjuvant therapy, surgical resection, and adjuvant therapy), as adjuvant therapy has its own potential advantages. With minimal residue of disease, and those cells preponderantly pre·pon·der·ant
Having superior weight, force, importance, or influence. See Synonyms at dominant.
pre·ponder·ant·ly adv. in their growth phase, postoperative remnants are maximally susceptible to chemo/radiotherapy. (24) This approach seems particularly reasonable, given our results with adjuvant therapy (Table 5) and recent developments favoring adjuvant chemotherapy Adjuvant chemotherapy
Treatment of the tumor with drugs after surgery to kill as many of the remaining cancer cells as possible.
Mentioned in: Neuroblastoma for lung cancer as a new standard of care. (25,26) Furthermore, if one adopts a neoadjuvant program of chemotherapy alone, then postoperative radiotherapy may be given in higher doses and in an uninterrupted fashion, if required.
Adjuvant therapy may be delivered as chemotherapy, radiotherapy, or combination chemoradiation therapy (sequential or concurrent). Impressive results have been achieved recently with adjuvant cisplatin-based chemotherapy. (25) Almost two decades ago, the Lung Cancer Study Group (27) demonstrated the ability of adjuvant radiotherapy to minimize local recurrence local recurrence Oncology The reappearance of the signs and Sx of CA at a site that was previously treated and responded to therapy. See Relapse. , at the cost of increased morbidity and non-cancer-related mortality rates. Also noted in that same study was a trend toward increased survival in stage III-A N2-positive patients. Subsequently, the Eastern Cooperative Oncology Group The Eastern Cooperative Oncology Group (ECOG) was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials. A cooperative group is a large network of researchers, physicians, and health care professionals at public and demonstrated that adjuvant, combination chemoradiation therapy (50.4 Gy) did not improve survival benefit over radiotherapy alone. (28) However, in our experience (Table 5), adjuvant radiotherapy, supplemented with sensitizing sen·si·tize
v. sen·si·tized, sen·si·tiz·ing, sen·si·tiz·es
1. To make sensitive: "The polarity principle . . . chemotherapy, was associated with the best 5-year survival.
Are we making progress in the treatment of NSCCL? In a 1992 review, (3) the University of Toronto Research at the University of Toronto has been responsible for the world's first electronic heart pacemaker, artificial larynx, single-lung transplant, nerve transplant, artificial pancreas, chemical laser, G-suit, the first practical electron microscope, the first cloning of T-cells, reported that N2-positive patients surviving negative mediastinoscopy and complete resection achieved a 5-year survival of 35%, (29) somewhat similar to our results. However, when operative mortality operative mortality The percentage of Pts who die while hospitalized during or after a surgical procedure , incomplete resection, or inability to resect resect /re·sect/ (-sekt´) to excise part or all of an organ or other structure.
To perform a resection on a part of the body. were included in their data analysis, 5-year survival dropped to 24% when mediastinoscopy was negative and 9% when mediastinoscopy was positive. (30) Thus, in our experience, where we have included all hospital deaths and have achieved survivals ranging from 31 to 61%, we do seem to be making some progress. When examining our results against the experiences of Toronto (3) and the University of Pennsylvania, (11) two points stand out in patient selection. First, treatment must be based on extent of disease. Second, treatment must also be based on clinical performance, as our results in patients with poor predicted postoperative FE[V.sub.1] well document. It bears repeating that there were no long-term survivors when preoperatively predicted postoperative FE[V.sub.1] was less than 1.0.
Our experience suggests that aggressive therapy for advanced stage (III, IV) NSCCL, including surgical resection, appears worthwhile in patients with reasonable pulmonary function and good-to-excellent performance status. (7,10) First, the appearance of advanced disease may be misleading, as Watanabe (6) documented false-positive CT scans for N2 disease in 39% of patients ultimately resected with stage I or II disease. Second, up-front surgery alone may yield a 5-year survival rate equal to 31%. Third, skillfully combining surgery with other neoadjuvant and/or adjuvant therapies may further improve 5-year survival to 45 to 61%.
We currently favor neoadjuvant, multiagent chemotherapy and combination adjuvant chemotherapy plus radiotherapy, when combination therapy is desired. With only a 1% treatment-related mortality rate associated with adjuvant chemotherapy, (25) benefit/risk analysis for stage III patients satisfactorily recovering from surgery favors treatment. Although future experience will more clearly define what combination of treatments are best, at present we have seen significant gains in 5-year survival with very low early mortality rates.
1. Ries LAG, Hawkey BF, Miller BA, et al. Cancer statistics review 1973-1988. Natl Cancer Inst NIH "Not invented here." See digispeak.
NIH - The United States National Institutes of Health. 1991. pp 1791-1789.
2. Williams DE, Pairolero PC, Davis CS, et al. Survival of patients surgically treated for stage I lung cancer. J Thorac Cardiovasc Surg 1981;82:70-76.
3. Miller JD, Gorenstein LA, Patterson G. Staging: The key to rational management of lung cancer. Ann Thorac Surg 1992;53:170-178.
4. Kiernan PD, Sheridan M, Hostetter AL, et al. Stage I non-small cell cancer of the lung: Results of surgical resection at Fairfax Hospital. Va Med Q 1993;120:146-149.
5. Martini N, Flehinger BJ. The role of surgery in N2 lung cancer. SCNA SCNA Sun Certified Network Administrator
SCNA Security Certified Network Architect
SCNA South Carolina Nurses Association
SCNA Saab Club of North America
SCNA Southern California Naturist Association
SCNA Sudden Cosmic Noise Absorption 1987;67:49-1037.
6. Watanabe Y, Shimizu J, Oda M, et al. Aggressive surgical intervention in N2 non-small cell cancer of the lung. Ann Thorac Surg 1991;51:253-261.
7. Kiernan PD, Sheridan M, Byrne WD, et al. Stage II and III-A non-small cell cancer of the lung: Results of surgical resection at INOVA Fairfax Hospital. Va Med Q 1994;121:172-178.
8. Daly BDT BDT
In currencies, this is the abbreviation for the Bangladesh Taka.
The currency market, also known as the Foreign Exchange market, is the largest financial market in the world, with a daily average volume of over US $1 trillion. , Mueller JD, Faling LJ, et al. N2 lung cancer: Outcome in patients with false negative computed tomographic scans of the chest. J Thorac Cardiovasc Surg 1993;105:904-911.
9. Naruke T, Goya T, Tsuchiya R, et al. The importance of surgery to non-small cell carcinoma of the lung with mediastinal lymph node metastasis metastasis /me·tas·ta·sis/ (me-tas´tah-sis) pl. metas´tases
1. transfer of disease from one organ or part of the body to another not directly connected with it, due either to transfer of pathogenic microorganisms or to . Ann Thorac Surg 1988;46:603-610.
10. Kiernan PD, Graling PR, Hettrick VL, et al. A pragmatic and successful approach to the treatment of non-small cell carcinoma of the lung. AORN AORN Association of periOperative Registered Nurses
AORN Association of Operating Room Nurses (name changed)
AORN As of Right Now 2004;80:840-862.
11. Machtay M, Lee JH, Stevenson JP, et al. Two commonly used neoadjuvant chemo che·mo
Chemotherapy or a chemotherapeutic treatment. and radiation therapy regimens for locally advanced stage III non-small cell lung carcinoma: Long-term results and associations with pathologic response. J Thorac Cardiovasc Surg 2004;127:108-113.
12. Inoue M, Sawabata N, Takeda S, et al. Results of surgical intervention for P-stage III-A (N2) non-small cell lung cancer Lung Cancer, Non-Small Cell Definition
Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.
There are two kinds of lung cancers, primary and secondary. : Acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor primary tumor A neoplasm which, in clinical parlance, is regarded as malignant, arising in one site and capable of giving rise to metastatic or secondary tumors. See Metastasis. Cf Tumor of unknown origin. in the upper lobe. J Thorac Cardiovasc Surg 2004;127:1100-1106.
13. Okada M, Nishio W, Sakamoto T, et al. Evolution of surgical outcomes for non-small cell lung cancer: time trends in 1,465 consecutive patients undergoing complete resection. Ann Thorac Surg 2004;77:1926-1931.
14. Keller SM, Vangel MG, Wagner H, et al. Prologed survival in patients with resected non-small cell lung cancer and single-level N2 disease. J Thorac Cardiovasc Surg 2004;128:130-137.
15. Tisi GM, Friedman PJ, Peters RM, et al. Clinical staging of primary lung cancer primary lung cancer Oncology Lung cancer arising in lung tissue–eg, trachea, bronchial tree, parenchyma. See Bronchoalveolar carcinoma, Small cell carcinoma, Squamous cell carcinoma. Cf Metastatic lung cancer. . Am Rev Respir Dis 1983;127:659-670.
16. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111:1710-1717.
17. Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718-1723.
18. American Joint Committee on Cancer Staging Manual. Philadelphia, Lippincott-Raven Publishing, 1997, 5th ed, pp 37-127.
19. Cox DR, and Oakes D. Analysis of Survival Data. London, Chapman and Hall Chapman and Hall was a British publishing house, founded in the first half of the 19th century by Edward Chapman and William Hall. Upon Hall's death in 1847, Chapman's cousin Frederic Chapman became partner in the company, of which he became sole manager upon the retirement of , 1984.
20. Peto R, Pike MC. Conservatism of the approximate sigma (O-E) 2-E in the log rank test for survival data in tumor-incidence data. Biometrics 1973;29:579-584.
21. Mountain CF. The biologic operability Operability is the ability to keep a system in a functioning and operating condition. In a computing systems environment with multiple systems this includes the ability of products, systems and business processes to work together to accomplish a common task such as finding and of stage III non-small cell lung cancer. Ann Thorac Surg 1985;40:60-64.
22. Martini N, Kris MG, Gralla RJ, et al. The effects of preoperative chemotherapy on the resectability of non-small cell lung cancer with mediastinal lymph node metastasis (N2M "Not too much." See digispeak. 0). Ann Thorac Surg 1988;45:370-379.
23. Martin J, Ginsberg RJ, Venkatraman ES, et al. Long-term results of combined-modality therapy in resectable re·sect·a·ble
Suitable for resection. non-small cell lung cancer. J Clin Oncol 2002;20:1989-1995.
24. Simpson-Herren L, Sanford A, Holmquist J. Effects of surgery in the cell kinetics of residual tumor. Cancer Treat Res 1976;60:1744-1760.
25. International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004;350:351-360.
26. Blum RH. Adjuvant chemotherapy for lung cancer: A new standard of care. N Engl J Med 2004;350:404-405.
27. Weisenburger T. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid epidermoid /epi·der·moid/ (-der´moid)
1. pertaining to or resembling the epidermis.
2. epidermoid cyst.
Composed of or resembling epidermal tissue. cancer of the lung. N Engl J Med 1986;315:1377-1381.
28. Keller S, Adak S, Wagner H, et al. A randomized ran·dom·ize
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment. trial of postoperative adjuvant therapy in patients with completely resected stage II or stage IIIA IIIA Internet Information Infrastructure Architecture
IIIA Integrated Intelligence Information Application
IIIA International Imaging Industry Association non-small cell lung cancer. N Engl J Med 2000;343:1217-1222.
29. Pearson FG. Lung cancer: The past twenty-five years. Chest 1986;89:200S-205S.
30. Pearson FG, Delarue NC, Ilves, TRJ TRJ Textile Research Journal
TRJ Therapeutic Recreation Journal (quarterly journal of the National Therapeutic Recreation Society)
TRJ The Romance Journal
TRJ Toal, Reutter, Jackman Refrigeration (Oxnard, CA) , et al. Significance of positive superior mediastinal nodes. identified at mediastinoscopy in patients with resectable cancer Resectable cancer
A tumor that can be surgically removed.
Mentioned in: Neuroblastoma of the lung. J Thorac Cardiovasc Surg 1982;83:1-11.
Believe those who seek the truth. Doubt those who find it. --Andre Gide
Paul D. Kiernan, MD, Michael J. Sheridan, SCD ScD [L.] Scien´tiae Doc´tor (Doctor of Science).
SCD 1 Sickle cell disease, see there 2 Subacute combined degeneration, see there 3 Sudden cardiac death, see there , James Lamberti, MD, Thomas LoRusso, MD, Vivian Hetrick, RN, Betty Vaughan, RN, and Paula Graling, RN
From the Inova Health System Inova Health System is a non-profit health organization based in Northern Virginia, USA. Hospitals under Inova provide most of the healthcare needs for citizens in Northern Virginia. The flagship hospital, Inova Fairfax Hospital, has won acclaims as one of the best hospitals in the nation. , Inova Fairfax Hospital, Sections of Thoracic Surgery Thoracic Surgery Definition
Thoracic surgery is the repair of organs located in the thorax, or chest. The thoracic cavity lies between the neck and the diaphragm, and contains the heart and lungs (cardiopulmonary system), the esophagus, trachea, pleura, , Epidemiology and Biostatistics, Pulmonary Medicine, and Thoracic Operating Room operating room
n. Abbr. OR
A room equipped for performing surgical operations. Nursing, Annandale, Virginia Annandale is an unincorporated place in Fairfax County, Virginia, United States. Recognized by the U.S. Census Bureau as a census-designated place (CDP), the community had a total population of 54,994 as of the 2000 census. .
Reprint requests to Dr. Kiernan, Section of Thoracic Surgery, Inova Fairfax Hospital, c/o Suite 301, 3301 Woodburn Road, Annandale, VA 22003. E-mail: firstname.lastname@example.org
Accepted May 10, 2005.
RELATED ARTICLE: Key Points
* One hundred seventeen patients underwent up-front surgery with respective hospital mortality rates and 5-year survival of 1.7% and 31%.
* Twenty-five patients, most with bulky mediastinal disease, underwent neoadjuvant therapy followed by surgical resection with respective rates of hospital mortality, complete pathologic response, major pathologic response, and 5-year survival of 0%, 16%, 64%, and 34%.
* Of the 16 patients undergoing neoadjuvant therapy who had complete pathologic response or significant downstaging of disease, 5-year survival was 61%.
* Among patients with an estimated postoperative FE[V.sub.1] < 1.0 L, there were no 5-year survivors (P < 0.0001).
* Adjuvant therapy was associated with improved 5-year survival (P = 0.03), particularly for combination chemotherapy and radiotherapy (P = 0.02).
Table 1. International (TNM) staging system for lung cancer (a) TNM descriptors Primary tumor (T) 0, No evidence of primary tumor 1, [less than or equal to] 3 cm in greatest dimension; not in main bronchus 2, > 3 cm in greatest dimension; involves main bronchus > 2 cm distal to carina; invades visceral pleura 3, of any size that directly invades chest wall, parietal or mediastinal pleura, pericardium, diaphragm, or tumor in the main bronchus < 2 cm distal to the carina without involvement of the carina 4, of any size that invades "vital mediastinum" such as heart, great vessels, trachea, esophagus, vertebral body, carina, tumor with malignant pleural or pericardial effusion, or with satellite tumor nodule(s) within ipsilateral primary tumor lobe of the lung Lymph nodes (N) 0, No metastasis 1, Metastasis to ipsilateral hilar and/or intrapulmonary nodes 2, Metastasis to ipsilateral mediastinal and/or subcarinal nodes 3, Metastasis to contralateral mediastinal or scalene or supraclavicular nodes Distant metastasis (M) 0, No distant metastasis 1, Distant metastasis, including nodule(s) in ipsilateral nonprimary tumor lobe(s) of the lung Stage groupings I-A T1N0M0 III-A T3N1M0 I-B T2N0N0 Any N2M0 II-A T1N1M0 III-B Any T4M0 II-B T2N1M0 Any N3M0 T3N0M0 IV Any M1 (a) TNM, tumor, node, metastasis. Adapted from Mountain CF. (16) Table 2. Advanced stage non-small cell carcinoma of the lung survival by predicted postoperative 1-second forced expiratory volume status. Inova Fairfax Hospital January 1, 1991, to October 31, 2003 (a) Kaplan-Meier survival Predicted postoperative No. estimates (SE) FE[V.sub.1] alive/dead 1 yr 2 yr 3 yr < 1.0 L 0/10 22 (14) 22 (14) * [greater than or equal to] 1.0 L 54/59 82 (4) 82 (4) 46 (5) Kaplan-Meier survival Predicted postoperative estimates (SE) FE[V.sub.1] 4 yr 5 yr P < 1.0 L * * <0.0001 [greater than or equal to] 1.0 L 38 (6) 36 (6) *Insufficient accrual time for comparison. (a) SE, standard error of Kaplan-Meier survival estimate. Table 3. Advanced stage non-small cell carcinoma of the lung survival by type of therapy, with and without neoadjuvant therapy. Inova Fairfax Hospital, January 1, 1991, to October 31, 2003 (a) Kaplan-Meier survival estimates (SE) Therapy No. alive/dead 1 yr 2 yr 3 yr A. Surgery up front 45/72 77 (4) 53 (5) 41 (5) vs Neoadj Rx + surgery 12/13 92 (5) 58 (11) 34 (11) B. Type neoadj Rx Chemo only 9/7 88 (8) 64 (13) 45 (14) vs Chemo + radiation 3/6 100 (0) 47 (19) * C. Therapy C1. Chemo + surgery 9/7 88 (8) 64 (13) 45 (14) vs C2. Surgery up front 45/72 77 (4) 53 (5) 41 (5) D. Chemo + surgery 5/5 100 (0) 78 (14) 39 (17) vs Surgery up front 45/72 77 (4) 53 (5) 41 (5) Kaplan-Meier survival estimates (SE) Therapy 4 yr 5 yr P A. Surgery up front 33 (5) 31 (5) vs 0.73 Neoadj Rx + surgery 34 (11) 34 (11) B. Type neoadj Rx Chemo only 45 (14) 45 (14) vs 0.19 Chemo + radiation * * C. Therapy C1. Chemo + surgery 45 (14) 45 (14) vs 0.32 C2. Surgery up front 33 (5) 31 (5) D. Chemo + surgery 39 (17) 39 (17) vs 0.41 Surgery up front 33 (5) 31 (5) *Insufficient accrual time for comparison. (a) Neoadj Rx, neoadjuvant therapy. Table 4. Advanced stage non-small cell carcinoma of the lung survival by final pathology stage. Inova Fairfax Hospital, January 1, 1991, to October 31, 2003 (a) Kaplan-Meier survival Final stage (No.) estimates (SE) (N = 142) No. alive/dead 1 yr 2 yr 3 yr CPR (a) (4) 3/1 75 (22) 75 (22) 75 (22) I-A (b) (3) 2/1 100 (0) 100 (0) 50 (35) I-B (c) (4) 1/3 75 (22) * * II-B (b) (5) 4/1 100 (0) 75 (22) 75 (22) III-A (71) 26/45 80 (5) 55 (6) 44 (6) III-B (40) 17/23 74 (7) 52 (9) 36 (9) IV (15) 4/11 86 (9) 50 (13) 29 (12) Kaplan-Meier survival estimates (SE) Disease category (No.) No. alive/dead 1 yr 2 yr 3 yr Downstaged (b) (16) 11/5 88 (9) 61 (15) 61 (15) N2 positive (68) 22/46 81 (5) 51 (6) 38 (6) Kaplan-Meier survival Final stage (No.) estimates (SE) (N = 142) 4 yr 5 yr P CPR (a) (4) 75 (22) * I-A (b) (3) 50 (35) 50 (35) I-B (c) (4) * * II-B (b) (5) * * 0.48 III-A (71) 33 (6) 31 (6) III-B (40) 36 (9) 36 (9) IV (15) 21 (11) 21 (11) Kaplan-Meier survival estimates (SE) Disease category (No.) 4 yr 5 yr P Downstaged (b) (16) 61 (15) 61 (15) 0.14 N2 positive (68) 28 (6) 25 (6) *Insufficient accrual time for comparison. (a) CPR, Complete pathologic response. (b) Downstaged by neoadjuvant therapy. Table 5. Advanced stage non-small cell carcinoma of the lung survival by postoperative (adjuvant) therapy. Inova Fairfax Hospital, January 1, 1991, to October 31, 2003 Kaplan-Meier survival Type postoperative therapy estimates (SE) (No.) (N = 142) No. alive/dead 1 yr 2 yr 3 yr Chemo + radiation (39) 21/18 95 (4) 67 (8) 55 (9) Chemo only (21) 11/10 84 (8) 50 (12) 39 (13) Radiation only (23) 6/17 72 (10) 50 (11) 39 (11) None (59) 19/40 71 (6) 47 (7) 31 (7) Kaplan-Meier survival Type postoperative therapy estimates (SE) (No.) (N = 142) 4 yr 5 yr P Chemo + radiation (39) 51 (9) 51 (9) Chemo only (21) 39 (13) 39 (13) 0.03* Radiation only (23) 20 (10) 20 (10) None (59) 26 (7) 21 (7) *For trend in postoperative therapy survival. For chemotherapy with radiation versus other postoperative therapies, P = 0.02.