kshivets o. lung cancer: optimal treatment strategies

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Lung Cancer: Optimal Treatment Strategies


  • The Open Lung Cancer Journal, 2009, 2, 12-23 12 Open Access Lung Cancer: Optimal Treatment Strategies Oleg Kshivets* Department of Thoracic Surgery, Klaipeda University, Klaipeda, Lithuania Abstract: Objective: Search of best treatment plan for non-small lung cancer (LC) patients (LCP) was realized. Methods: In trial (1985-2008) the data of consecutive 535 LCP after complete resections (R0) (age=57.38.2 years; male- 482, female-53; tumor diameter: D=4.72.2 cm; pneumonectomies-222, lobectomies-313, combined procedures with re- section of pericardium, atrium, aorta, VCS, carina, diaphragm, ribs-155; only surgery-S-316, adjuvant chemoimmunora- diotherapy-AT-117: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy, postoperative radiotherapy 45- 50Gy-RT-102; squamous-341, adenocarcinoma-153, large cell-41; stage IA-105, IB-130, IIA-21, IIB-122, IIIA-116, IIIB- 41; T1-150, T2-230, T3-114, T4-41; N0-310, N1-118, N2-107; G1-126, G2-152, G3-257) were reviewed. Variables se- lected for 5-year survival (5YS) study were input levels of blood, biochemic and hemostatic factors, sex, age, TNMG, D. Survival curves were estimated by Kaplan-Meier method. Differences in curves between groups were evaluated using a log-rank test. Neural networks computing, Cox regression, clustering, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity. Results: For total of 535 LCP overall life span (LS) was 1723.31294.9 days and cumulative 5YS reached 63.6%, 10 years 52.8%. 304 LCP (LS=2597.31037 days) lived more than 5 years without LC progressing. 186 LCP (LS=559.8383.1 days) died because of LC during first 5 years after surgery. 5YS of LCP with N1-2 was superior signifi- cantly after AT (65.6%) compared with RT (39.5%) (P=0.0003 by log-rank test) and S (28.3%) (P=0.000). Cox modeling displayed that 5YS significantly depended on: phase transition (PT)early-invasive LC, PT N0-N12, AT, age, weight, histology, G, T, D, blood cell subpopulations, cell ratio factors, ESS, prothrombin index, heparin tolerance, recalcification time, bilirubin, (P=0.000-0.046). Neural networks computing, genetic algorithm selection and bootstrap simulation re- vealed relationships between 5YS and PT N0-N12 (rank=1), procedure type, G, T, histology, AT, PT early-invasive LC, RT, S, sex, ESS, prothrombin index, fibrinogen, Hb, protein, weight, lymphocytes. Correct prediction of 5YS was 99.6% by neural networks computing (error=0.045; urea under ROC curve=0.995). Conclusion: Optimal treatment strategies for LCP are: 1) screening and early detection of LC; 2) availability of experi- enced surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymphadenec- tomy for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable progno- sis. INTRODUCTION after clinical trials showed approximately 5-15% improve- ment in overall survival for those with higher risk disease, Lung Cancer is a global problem of the mankind. In the especially for stage II-IIIA [4,5]. Generally, cancer has im- world 1.5 million new patients with lung cancer are diag- munosuppressive effects on patients immune circuit [6]. nosed each year, from which 85-90% have already died. Ap- Surgery, chemotherapy and irradiation themselves perturb proximately 80-85% of these tumors are non-small cell his- baseline immune circuit [7]. Clinically, in the total popula- tological type, including adenocarcinomas, squamous cell tion it is known that poor baseline cytotoxic function of pa- and large cell carcinomas. Non-small cell lung cancer (LC) tient immune cells correlates with a higher long-term rate of is the main cause of death from cancer, and real 5-year sur- cancer relapses and generalization after radical procedures vival (5YS) across all stages of the disease is approximately [8]. 14% in the USA and 10% in Europe [1,2]. At the present, radical surgery is generally regarded as the best treatment One of the most perspective directions developed to en- option, but only approximately 30-50% of tumors are suit- hance the efficacy of surgery is the combination of chemo- able for potentially curative resection depending on quality therapy, irradiation and immunotherapy or gene therapy of diagnostics of LC and aggression and skill of regional which offers the advantage of exposing LC cell population thoracic surgeons [1,3]. Adjuvant chemotherapy has recently for drugs and immune factors, thus obviating cancer cell- become a new standard of care for patients with LC (LCP) cycle cytotoxic and host-immunoprotective effects [1,9]. Nevertheless, very few studies have demonstrated convinc- ing clinical results. We developed optimal treatment strate- *Address correspondence to this author at the Thoracic Surgery Department, gies that incorporate bolus chemotherapy, irradiation and Klaipeda University Hospital, Vingio: 16, P/D 1017, Klaipeda, LT95188, immunotherapy after radical, aggressive en-block surgery Lithuania; Tel: (370)60878390; E-mail: [email protected] and mediastinal lymph node dissection. 1876-8199/09 2009 Bentham Open
  • Fiber Deposition in Human Lungs The Open Lung Cancer Journal, 2009, Volume 2 13 PATIENTS AND METHODS in 105, IB in 130, IIA - in 21, IIB in 122, IIIA - in 116 and IIIB in 41 patients; the pathological T stage was T1 in We performed a review of prospectively collected data- 150, T2 - in 230, T3 - in 114, T4 - in 41 cases; the pathologi- base of European patients undergoing the complete (R0) cal N stage was N0 in 310, N1 - in 118, N2 - in 107 patients. pulmonary resections for LC between August 1985 and No- The tumor differentiation was graded as G1 in 126, G2 - in vember 2008. 535 consecutive LCP (male 482, female 152, G3 - in 257 cases. 53; age=57.38.2 years, tumor size=4.72.2 cm) (meanstandard deviation) entered this trial. Patients were After surgery postoperative chemoimmunoradiotherapy not considered eligible if they had N3 lymph node metasta- or radiotherapy were accomplished LCP in ECOG perform- sis, stage IV (nonregional lymph nodes metastases, distant ance status 0 or 1. metastases, carcinomatous pleurisy, carcinomatosis), previ- All patients (535 LCP) were divided between the three ous treatment with chemotherapy, immunotherapy or radio- protocol treatment: 1) surgery and adjuvant chemoim- therapy or if there were two primary tumors at the time of munoradiotherapy (117 LCP group A) (age=57.79.0 diagnosis. LCP after non-radical procedures and patients, years; males - 108, females - 9; tumor size=5.52.5 cm); 2) who died postoperatively, were excluded to provide a homo- surgery and postoperative radiotherapy (102 LCP group B) geneous patient group. The preoperative staging protocol (age=57.77.5 years; males - 91, females - 11; tumor included clinical history, physical examination, complete size=4.72.1 cm); 3) surgery alone without any adjuvant blood count with differentials, biochemistry and electrolyte treatment (316 LCP group C) (age=57.18.1 years; males- panel, chest X-rays, rntgenoesophagogastroscopy, com- 283, females - 33; tumor size=4.32.1 cm) the control puted tomography scan of thorax, abdominal ultrasound, group. All patients completed adjuvant therapy (chemoim- fibrobronchoscopy, electrocardiogram. Computed tomogra- munoradiotherapy or radiotherapy). phy scan of abdomen, liver and bone radionuclide scan were performed whenever needed. Mediastinoscopy was not used. After complete resections 102 LCP received radiotherapy All LCP were diagnosed with histologically confirmed LC. (60CO; ROKUS, Russia) with a total tumor dose 45-50 Gy All had measurable tumor and ECOG performance status 0 starting 2-4 weeks after surgery (group B). Radiation con- or 1. Before any treatment each patient