IIIA Non-small Cell Lung Carcinoma Research Articles

Pretreatment Tumor Growth Rate and Radiological Response as Predictive Markers of Pathological Response and Survival in Patients with Resectable Lung Cancer Treated by Neoadjuvant Treatment.

Predictive biomarkers associated with pathological response, progression precluding surgery, and/or recurrence after surgery are needed for patients with resectable non-small cell lung carcinoma (NSCLC) treated by neoadjuvant treatment. We evaluated the clinical impact of the pretreatment tumor growth rate (TGR0) and radiological response for patients with resectable NSCLC treated with neoadjuvant therapies. Consecutive patients with resectable stage IB (≥4 cm) to IIIA NSCLC treated by neoadjuvant platinum-doublet chemotherapy with or without nivolumab at our tertiary center were retrospectively analyzed. TGR0 and RECIST objective responses were determined. Multivariable analyses identified independent predictors of event-free survival (EFS), overall survival (OS), and major pathological response (MPR). Between November 2017 and December 2022, 32 patients (mean [SD] age, 63.8 [8.0] years) were included. At a median follow-up of 54.8 months (95% CI, 42.3-60.4 months), eleven patients (34%) experienced progression or recurrence, and twelve deaths (38%) were recorded. The TGR0 cutoff of 30%/month remained the only independent factor associated with EFS (HR = 0.04; 95% CI, 0.01-0.3; p = 0.003) and OS (HR = 0.2; 95% CI, 0.03-0.7; p = 0.01). The TGR0 cut-off had a mean time-dependent AUC of 0.83 (95% CI, 0.64-0.95) and 0.80 (95% CI, 0.62-0.97) for predicting EFS and OS, respectively. Fifteen of 26 resection cases (58%) showed MPR including nine with pathological complete responses (35%). Only the objective response of the primary tumor was associated with MPR (OR = 27.5; 95% CI, 2.6-289.1; p = 0.006). Assessment of TGR0 can identify patients who should benefit from neoadjuvant treatment. A tumor objective response might be a predictor of MPR after neoadjuvant treatment, which will help to adapt surgical management.

Comprehensive Characterization of Stage IIIA Non-Small Cell Lung Carcinoma.

IntroductionHeterogeneity of non-small cell lung carcinoma (NSCLC) among patients is currently not well studied. Pathologic markers and staging systems have not been a precise predictor of the prognosis of an individual patient. Hence, we hypothesize to develop a transcript-based signature to categorize stage IIIA-NSCLC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), plus identify markers that could indicate the prognosis of the disease.MethodsHuman Transcriptome Array 2.0 (HTA) and NanoString nCounter® platform were used for high-throughput gene-expression profiling. Initially, we profiled stage IIIA-NSCLC through HTA and validated through NanoString. Additionally, two metastatic markers SPP1 and CDH2 were validated in 47 NSCLC stage IIIA samples through real-time PCR.ResultsWe observed distinct gene clusters in LUAD and LUSC with down-regulation of six genes and up-regulation of 57 genes through HTA. Ninety-six transcripts were randomly selected after analyzing HTA data and validated on the NanoString platform. We found 40 differentially expressed transcripts that categorized NSCLC into LUAD and LUSC. SPP1 is significantly overexpressed (4.311±1.27 fold in LUAD and 13.41±3.82 fold in LUSC compared to control), and the CDH2 transcript was significantly overexpressed (11.53 ± 4.027-fold compared to control) only in LUSC.DiscussionThese markers enable us to categorize stage IIIA NSCLC into LUAD and LUSC plus these markers may be helpful to understand the pathophysiology of NSCLC. However, more data required to make these findings useful in general clinical practice.

Variants in Epithelial-Mesenchymal Transition and Immune Checkpoint Genes Are Associated With Immune Cell Profiles and Predict Survival in Non-Small Cell Lung Cancer.

Identification of gene mutations that are indicative of epithelial-mesenchymal transition and a noninflammatory immune phenotype may be important for predicting response to immune checkpoint inhibitors. To evaluate the utility of multiplex immunofluorescence for immune profiling and to determine the relationships among tumor immune checkpoint and epithelial-mesenchymal transition genomic profiles and the clinical outcomes of patients with nonmetastatic non-small cell lung cancer. Tissue microarrays containing 164 primary tumor specimens from patients with stages I to IIIA non-small cell lung carcinoma were examined by multiplex immunofluorescence and image analysis to determine the expression of programmed death ligand-1 (PD-L1) on malignant cells, CD68+ macrophages, and cells expressing the immune markers CD3, CD8, CD57, CD45RO, FOXP3, PD-1, and CD20. Immune phenotype data were tested for correlations with clinicopathologic characteristics, somatic and germline genetic variants, and outcome. A high percentage of PD-L1+ malignant cells was associated with clinicopathologic characteristics, and high density of CD3+PD-1+ T cells was associated with metastasis, suggesting that these phenotypes may be clinically useful to identify patients who will likely benefit from immunotherapy. We also found that ZEB2 mutations were a proxy for immunologic ignorance and immune tolerance microenvironments and may predict response to checkpoint inhibitors. A multivariate Cox regression model predicted a lower risk of death for patients with a high density of CD3+CD45RO+ memory T cells, carriers of allele G of CTLA4 variant rs231775, and those whose tumors do not have ZEB2 mutations. Genetic variants in epithelial-mesenchymal transition and immune checkpoint genes are associated with immune cell profiles and may predict patient outcomes and response to immune checkpoint blockade.

Implantation of computed tomography-guided Iodine-125 seeds in combination with chemotherapy for the treatment of stage III non-small cell lung cancer.

PurposeWe investigated the role of computed tomography (CT)-guided Iodine-125 (125I) seed implantation in combination with chemotherapy for the treatment of stage III non-small cell lung carcinoma (NSCLC).Material and methodsThe data from 182 patients with stage III NSCLC who were treated with radioactive 125I seed implantation between June 2002 and June 2009, and who received sequential platinum-based combination chemotherapy using the most common combination of platinum and gemcitabine, were retrospectively reviewed. The 182 patients received a prescribed dose of 110.0 Gy, with a median radioactivity of 0.70 mCi (range, 0.64-0.78 mCi, 2.37-3.26 × 107 Bq). The median number of 125I seeds was 38 pellets (range, 6-105 pellets). The median post-operation dose covering 100% of the target volume (D100) was 94.5 Gy (range, 54.6-125.5 Gy). The median D90 was 143.0 Gy (range, 121.6-184.0).ResultsThe 1-, 3-, and 5-year overall survival rates were 83.35%, 25.57%, and 11.34%, respectively; the median survival time was 24.76 months. At 1, 3, and 5 years, the local control rates were 92.01%, 86.51%, and 76.45%, respectively; the median local control time was 25.28 months. For patients with stage IIIA and IIIB NSCLC, the median survival times were 26.67 and 24.59 months, respectively (p = 0.2). Pre-treatment hemoglobin level, tumor volume, and postoperative D100 were significantly associated with survival. A total of 24 patients experienced pneumothorax (incidence rate, 13.20%), and 17 patients experienced hemothorax (incidence rate, 5.0%).ConclusionsCT-guided 125I seed implantation combined with chemotherapy is an effective, minimally invasive method for the treatment of stage III NSCLC. Furthermore, hemoglobin levels before treatment, D100, and the maximum diameter of the tumor may be prognostic factors in patients with NSCLC treated sequentially with radiotherapy and chemotherapy.

Higher Versus Standard Preoperative Radiation in the Trimodality Treatment of Stage IIIa Lung Cancer

The management of potentially resectable stage III non-small cell lung carcinoma (NSCLC) is controversial. Options include induction chemotherapy or induction chemoradiation followed by resection, or chemoradiation without surgery. No trial has compared the outcomes of induction chemoradiation using different radiation doses. We reviewed our experience involving patients with clinical stage III disease treated with trimodality therapy involving two radiation strategies to determine the response rates, operative results, recurrence patterns, and long-term survival. A retrospective review was made of consecutive stage III NSCLC patients treated from 2004 to 2011. Fifty-two patients with clinical stage IIIa NSCLC were treated with trimodality therapy. Eighteen patients were treated to doses of 60 Gy or higher, and 34 to lower doses (45, 50, or 54 Gy). There were significantly more postoperative complications in the higher radiation group (p < 0.001). Pathologic complete response (50% versus 15%, p = 0.016) and mediastinal nodal clearance (75% versus 42%, p = 0.254) rates were also higher in the high-dose group. That did not, however, translate into better disease-free and overall survival rates. Importantly, long-term noncancer mortality was significantly higher after higher dose preoperative radiation therapy. In this series of patients with clinical stage IIIa NSCLC treated with trimodality therapy, a higher dose of preoperative radiation therapy resulted in better response rates but that did not translate to better cancer-specific survival. Of significance, we observed a notably higher delayed noncancer mortality in the high-dose group.

Morbidity and Mortality after Major Pulmonary Resections in Patients with Locally Advanced Stage IIIA Non-small Cell Lung Carcinoma Who Underwent Induction Therapy

The optimal treatment for patients with locally advanced stage IIIA non-small cell lung carcinoma (NSCLC) remains controversial, but induction therapy is increasingly used. The aim of this study was to evaluate mortality, morbidity, hospital stay and frequency of postoperative complications in stage IIIA NSCLC patients that underwent major pulmonary resections after neoadjuvant chemotherapy or chemoradiation. We conducted a retrospective analysis of all patients who underwent major pulmonary resections after induction therapy for locally advanced NSCLC from October 2009 to February 2014. Forty-one patients were included in the study. Complete resection was achieved in 40 patients (97.5%). A complete pathologic response was seen in 10 patients (24.4%). Mean hospital stay was 17.7 days (ranged 5-129 days). Early (in-hospital) mortality occurred in 2.4% (one patient after bilobectomy), late (six months) mortality in 4.9% (two patients after right pneumonectomy and bilobectomy), and overall morbidity in 58.5% (24 patients). Postoperative complications included: bronchopleural fistula (BPF) with empyema - three patients, empyema without BPF - five patients, air leak - eight patients, atrial fibrillation - eight patients, pneumonia - eight patients, and lobar atelectasis - four patients. Following neoadjuvant therapy for stage IIIA NSCLC, pneumonectomy can be performed with low early and late mortality (0% and 5.8%, respectively), bilobectomy is a high risk operation (16.7% early and 16.7% late mortality); and lobectomy a low risk operation (0% early and late mortality). The need for major pulmonary resections should not be a reason to exclude patients from a potentially curative procedure if it can be performed with acceptable morbidity and mortality rates at an experienced medical centre.

Isolated Left Main Coronary Artery Stenosis after Thoracic Radiation Therapy: To Operate or Not to Operate

Radiation therapy of neoplasms involving the chest or mediastinum results in a wide spectrum of cardiac complications including coronary artery disease, which can present in patients with few or no traditional cardiac risk factors. We report a case of radiation induced coronary artery disease in a 60-year-old female with a history of stage IIIA nonsmall cell lung carcinoma which was diagnosed eight years earlier and treated with chemotherapy and radiotherapy. She presented to the hospital with atypical chest pain that had occurred intermittently over the preceding week. Her initial electrocardiogram and cardiac enzymes were within normal limits. However, following an indeterminate exercise nuclear stress test, she developed chest pain and elevated cardiac enzymes. Coronary angiography demonstrated 90% stenosis of the left main coronary artery ostium, without any evidence of atherosclerotic disease or stenosis in other coronary arteries. She underwent surgical revascularization, which revealed dense adhesions surrounding the heart. During surgery, she developed severe bleeding and died. Coronary artery disease can present within years of radiation exposure, and ostial lesions are typical. Treatment is often challenging because of the effects of radiation on other tissues and the risks of revascularization procedures. Therefore, a multidisciplinary team approach should be considered.

Chemotherapy for Non-Small-Cell Lung Carcinoma: From a Blanket Approach to Individual Therapy

Only one third of patients with non-small-cell lung carcinoma (NSCLC) present with early-stage disease that is amenable to potentially curative resection and adjuvant therapy. Unfortunately, even in stage I NSCLC, 5-year survival rates are in the range of 55 to 72%. For unresectable disease in stages IIIB and IV, 5-year survival rates are < 5%. Postoperative chemotherapy (adjuvant chemotherapy) using cisplatin-based regimens has become the standard of care for resected stage II to IIIA NSCLC. However, adjuvant chemotherapy may be harmful in stage IA NSCLC, and its role for stage 1B is controversial. There are no conclusive data showing superiority of neoadjuvant chemotherapy (given prior to surgery) over adjuvant chemotherapy (given after surgery) or vice versa in early-stage NSCLC. Several emerging TARGETED therapy agents [e.g., inhibitors of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), or tyrosine kinase], and combination chemotherapy regimens are currently being evaluated in NSCLC. Specific patient subpopulation characteristics (including EGFR mutations) may be prognostically important to identify potential responders (or nonresponders) to therapy. This review will focus on chemotherapeutic approaches to treat both early stage (adjuvant and neoadjuvant chemotherapy) and metastatic disease including the use of maintenance therapy and novel agents.

Factors associated with local and distant recurrence and survival in patients with resected nonsmall cell lung cancer

This study assessed the impact of surgical, histopathologic and patient-related factors on the risks of local and distant recurrence and overall survival for patients with stages I through IIIA nonsmall cell lung carcinoma (NSCLC) undergoing definitive resection with or without adjuvant chemotherapy. This study included 373 consecutive patients treated between 2000 and 2005 who did not receive adjuvant or neoadjuvant radiotherapy, had at least 3 months of follow-up, and did not have a history of other cancers within 5 years of the diagnosis of their NSCLC. Of these, 52% had pathologic stage IA disease, 30% had stage IB, 5% had stage IIA, 8% had stage IIB and 5% had stage III disease. Forty-four patients received chemotherapy. The median follow-up was 33 months. Local failure rates at 2 years, 3 years, and 5 years were 16%, 22%, and 32%, respectively; distant recurrence rates were 13%, 15%, and 21%, respectively. Multivariable analysis revealed that local recurrence was significantly associated with the presence of lymphatic or vascular invasion (LVI), the use of chemotherapy, and having diabetes; distant recurrence was significantly higher in patients with nonsquamous cell histology, those undergoing pneumonectomy, and those with more advanced TNM stage. Survival was significantly associated with age, history of myocardial infarction, performance of a pneumonectomy, histology, LVI, and the number of positive N1 lymph nodes. Local recurrence was the predominant type of failure in this series. Patient with diabetes or LVI may benefit from close surveillance and aggressive therapy of asymptomatic local recurrences, especially when chemotherapy is given in addition to surgery.

114: A Phase II Trial of Concurrent Paclitaxel and Carboplatin and Thoracic Radiotherapy in Resected Stage II and IIIA Non-Small Cell Lung Carcinoma

114: A Phase II Trial of Concurrent Paclitaxel and Carboplatin and Thoracic Radiotherapy in Resected Stage II and IIIA Non-Small Cell Lung Carcinoma

Prognostic impact of Deoxyribonucleic acid (DNA) image analysis cytometry and immunohistochemical expression of Ki67 in surgically resected non-small cell lung cancers

Background: The aim of the present study was to evaluate the prognostic significance of DNA ploidy and Ki67 expression in non-small cell lung carcinoma (NSCLC). Methods: This prospective study included 96 patients with stages I–IIIA NSCLC who underwent surgical excision. DNA image analysis cytometry was applied on imprints. Calculation of the DNA index (DI) and the 5c exceeding rate (5cER) was performed and the histograms were classified as peridiploid, peritetraploid, and x-ploid–multiploid. The Ki67 immunoreactivity was determined according to the avidin–biotin complex immunoperoxidase method. Results: DNA histogram classification disclosed 30 peridiploid cases, 15 peritetraploid and 51 x-ploid–multiploid. Forty-eight cases (50%) had 5cER > 5%. The Ki67 immunoreactivity was below 25% in 53 tumors (62.4%) and above 25% in 32 (32.6%). Our results revealed the existence of a statistically significant relationship of DNA ploidy with nodal status ( p = 0.042) and grade ( p = 0.005). Adenocarcinomas and large cell carcinomas were more frequently encountered in x-ploid–multiploid tumors as compared to squamous cell carcinomas, which were more frequently peridiploid ( p = 0.003). 5cER showed statistically significant association with nodal status ( p = 0.037). Univariate analysis with respect to survival revealed significant association with stage ( p < 0.001), nodal status ( p < 0.001), tumor status ( p < 0.001), DNA ploidy ( p = 0.008) and 5cER ( p = 0.0124). Multivariate analysis revealed stage and ploidy status as independent factors: peridiploid tumors were associated with better survival as compared to x-ploid–multiploid tumors ( p = 0.022). Conclusion: Our results suggest that DNA ploidy, as determined by image analysis, provides an independent prognostic parameter for patients with NSCLC and thus, could be used to identify a subset of patients with more aggressive tumors.

P-211 Stage IIIA non-small cell lung carcinoma (NSCLC): Treatmentchoices following neoadjuvant chemotherapy

P-211 Stage IIIA non-small cell lung carcinoma (NSCLC): Treatmentchoices following neoadjuvant chemotherapy

The combination of gemcitabine and cisplatin as neoadjuvant chemotherapy for early stage non-small cell lung carcinoma (NSCLC): an interim analysis of a phase II trial

7303 Background: The objectives of this ongoing, open-label, single-arm, phase II trial were to evaluate the efficacy and safety of gemcitabine/cisplatin as neoadjuvant chemotherapy in patients with operable, early stage NSCLC. Methods: Chemonaive patients >18 to 70 years old with stage IB, IIA-B, and IIIA NSCLC and an ECOG performance status (PS) of 0–1 received gemcitabine (1000 mg/m2; iv) on days 1 and 8 plus cisplatin (75 mg/m2; iv) on day 1. The treatment was administered on a 21-day treatment cycle for 3 cycles, followed by surgery or radiotherapy if medically unfit for surgery. The follow-up period was 12 months after surgery. Results: At the time of this analysis, 43 patients, with a median age of 55.8 years, were enrolled. Most patients (47%) had stage IB, while 26% of the patients had stage II and 28% had stage IIIA disease. N0 and N2 nodal disease was observed in 74% and 26% of the patients, respectively. Overall, 70% of the patients had T2 primary tumors, 26% had T3, and 2% of the patients each had T1 and T0. At baseline, 19 patients had a PS of 0 and 24 patients had a PS of 1. The PS of the patients improved in each visit during the follow-up period; 33 (77%) patients were fully active and asymptomatic (PS 0) at the final visit. Of the 38 patients evaluable for clinical tumor response, 21 (55%) had partial response and 15 (40%) had stable disease, while only 2 (5%) had progressive disease. NCI-CTC grade 3–4 hematologic toxicities included neutropenia in 24 (56%) patients and thrombocytopenia in 6 (14%) patients. Non-hematologic toxicities were acceptable. Data on 24 of 43 patients were analyzed for surgery. The tumor resection rate was 88% (21 of 24). Two of 24 patients (8%) received radiotherapy following chemotherapy. Conclusion: Preliminary results show that the combination of gemcitabine/cisplatin is an effective and tolerable neoadjuvant treatment for patients with operable, early stage NSCLC. The final analysis of the data, including pathological complete response rate as well as the expression and correlation of the prognostic factors erbB-2, VEGF, Ki67, and p53 with efficacy parameters, will be presented at the meeting. No significant financial relationships to disclose.

Results of a phase I dose‐escalation study using three‐dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma

The objective of this study was to report the results of a Phase I dose-escalation study using three-dimensional conformal radiation therapy (3D-CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC). Between 1991 and 2003, 104 patients were enrolled for 3D-CRT at Memorial Sloan-Kettering Cancer Center. The median patient age was 69 years. Twenty-eight percent of patients had Stage I-II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses < or = 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity. After an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2-year local control rate was 52%, the disease-free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received > or = 80.0 Gy. The MTD of 3D-CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy.

Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven Stage IIIA(N2) nonsmall cell lung carcinoma: a Phase II multicenter study.

The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC). Forty-nine chemotherapy-naïve patients (median age, 61 years; World Health Organization performance status, 0-1) with biopsy-proven Stage IIIA(N2) disease received 1000 mg/m(2) gemcitabine, 125 mg/m(2) paclitaxel, and 50 mg/m(2) cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy. Grade 3-4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3-4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty-six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1-year survival rate of 85%. GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored.

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma

Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.

182 Chemoradiation with or without surgery for stage IIIA non-small cell lung carcinoma (NSCLC): A comparison of survival and patterns of failure

182 Chemoradiation with or without surgery for stage IIIA non-small cell lung carcinoma (NSCLC): A comparison of survival and patterns of failure

Multimodality treatment of stage IIIA non-small-cell lung carcinoma: a critical review of the literature and strategies for future research.

Stage IIIA non-small-cell lung carcinoma (NSCLC) is composed of regionally advanced yet potentially resectable disease. Many trials have evaluated a variety of therapeutic strategies. Most have been single-arm phase II trials, although a number of comparative phase III trials have also been performed. This review critically evaluates the existing literature on the treatment of stage IIIA NSCLC, particularly the various multimodality approaches that have been used. A review of the existing literature does not establish the optimal treatment of stage IIIA NSCLC. Although radiation therapy alone remains the most commonly administered therapy for apparently unresectable disease, the status of radiation as a "standard" therapy can be seriously challenged based on existing data. Similarly, although a number of studies have established that surgical resection is clearly feasible in selected patients with stage IIIA disease, the efficacy of surgery also remains to be definitively established. Many studies have explored neoadjuvant chemotherapy, either in conjunction with radiation or surgery, with results that are best described as conflicting and controversial. Without question, randomized phase III trials are required at this time to define what is to be considered optimal treatment. An attempt is made to define the most important questions that should be addressed in future phase III trials. Additionally, a number of study designs are suggested to best answer the therapeutic questions posed.