IIIB Non-small Cell Lung Cancer Research Articles

Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1=weight loss (WL); group 2=weight preservation/gain (WP) for comparative analyses. Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT.

10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)—A multicenter phase-II trial (CISTAXOL)

BackgroundInduction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German–French phase-II trial with trimodality. Patients and methodsMediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50mg/m2 day 1+8) and paclitaxel (175mg/m2d1) qd 22. Concurrent CTx/RTx followed: 45Gy (1.5Gy bid) with cisplatin 50mg/m2 day 2+9 and etoposide 100mg/m2 d 4–6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20Gy; 2Gy qd) followed. Here we report 10-year-LTS for this cohort. ResultsAll 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33–69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment – histopathology (squamous/adeno) – age (<50/≥50) – Charlson-CI: 1/>1 – BMI (≥25/<25) – pack years smoking (≥10/<10); treatment-dependent – R0/no-R0. ConclusionsThis regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).

A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer

BackgroundCetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). MethodsPatients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). ResultsForty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. ConclusionsThe addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

Recurrence of Paraneoplastic Membranous Glomerulonephritis following Chemoradiation in a Man with Non-Small-Cell Lung Carcinoma

Membranous glomerulonephritis can occur as a rare paraneoplastic complication of human cancers. In this case report, we describe a patient who presented acutely with symptoms of the nephrotic syndrome including heavy proteinuria and anasarca. He was subsequently diagnosed with membranous glomerulonephritis, and soon afterwards was found to have stage IIIB non-small cell lung cancer. Following chemoradiation therapy, both the patient’s cancer and membranous glomerulonephritis dramatically improved. However, approximately 14 months following his initial presentation, the patient was found to have a recurrence of his nephrotic-range proteinuria which corresponded temporally with recurrence of his cancer. We present details of the case and a review of the relevant scientific literature.

Expression of KISS1 and KISS1R (GPR54) may be used as favorable prognostic markers for patients with non-small cell lung cancer

Lung cancer is the most commonly diagnosed cancer worldwide. Loss of KISS1 expression has been associated with progression and poor prognosis of various cancers, however, the precise role of KISS1 expression in non-small cell lung cancer (NSCLC) is not well defined. KISS1 receptor (KISS1R, also named GPR54) coupled to KISS1, has been shown to play a pivotal role in suppressing cancer metastasis. In this study, 56 NSCLC specimens were divided into stage IIIB (locally advanced) and stage IV (metastatic). The mRNA and protein levels of KISS1 and KISS1R in cancer tissues were found to be lower compared to that in normal tissues using RT-PCR and western blot analysis, respectively. In addition, the expression of both KISS1 and KISS1R in stage IV NSCLC was lower compared to that in stage IIIB stage NSCLC. The cumulative survival rate of the patients with KISS1 or KISS1R expression was significantly higher compared to that without expression. KISS1 or KISS1R expression in NSCLC can be used to indicate favorable prognosis for disease outcome. Metastin, the product of the KISS1 gene, was lower in the serum of patients with stage IV NSCLC compared to that in stage IIIB NSCLC.

A three-drug induction chemotherapy with gemcitabine, carboplatin, and paclitaxel for stage III non-small cell lung cancer

The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18-75 years, ECOG PS 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m(2) on day 1, and i.v. gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3-G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2-72), median PFS was 10.5 months (95 % CI 9.9-11.4) and median OS was 21.1 months (95 % CI 19.7-22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2-19.7) and a median OS of 25.5 months (95 % CI 23.0-28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.

Gefitinib in combination with prednisolone to avoid interstitial lung disease during non-small cell lung cancer treatment: A case report

Gefitinib-induced interstitial lung disease (ILD) is a rare but lethal drug adverse event, which usually leads to the withdrawal of gefitinib and causes complications with anticancer treatment. In this study, gefitinib administration combined with prednisolone in a female with stage IIIb non-small cell lung cancer (NSCLC) produced a good outcome without inducing ILD. The results suggested that combined administration of gefitinib with glucocorticoids may be an efficient method to treat NSCLC while avoiding complications with ILD.

Peripheral Immune Cell Gene Expression Changes in Advanced Non-Small Cell Lung Cancer Patients Treated with First Line Combination Chemotherapy

IntroductionIncreasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.MethodsTo test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.ResultsSixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.ConclusionsOur results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.

Outcome of endobronchial electrocautery versus external beam radiotherapy or both together in the palliative management of non-small cell lung cancer

BackgroundApproximately 75% of patients with non-small cell lung cancer (NSCLC) present with locally advanced or metastatic disease which renders them inoperable and virtually incurable. Whene the aim of treatment is palliation, radiotherapy and bronchotherapeutic procedures are often recommended. Aim of the workTo evaluate the outcome of endobronchial electrocautery and or external beam radiotherapy (XRT) in the palliative treatment of patients with inoperable non-small cell lung cancer. Patient and methods40 patients with unresectable stage IIIA and IIIB NSCLC, 33 males and 7 females, their mean age of 60.82±6.23years were recruited in the study. Eligible patients were randomly classified into 3 groups: Group I: included 11 patients who received combined external irradiation (XRT) with end bronchial electro cautery, Group II: included 11 patients who received end bronchial electrocautery without external irradiation XRT, Group III: including 18 patients who received external palliative irradiation alone. Evaluation of chest symptoms, chest CT, PFTs, ABGs and quality of life outcomes were done before the interventional bronchoscopy and XRT therapies then one week and one month after the end of treatment. ResultsAs regards improvement of endobronchial symptoms; one week after completion of treatment, Group III patients was significantly lesser than Groups I and II and one month after treatment, there was no significant difference between all patient groups except in cough which was in Group III of lesser improvement than Groups I and II. As regards patients who had atelectasis before starting treatment: Group I showed 100% disappearance of atelectasis either complete or partial one month after completion of treatment while Group II showed 77.77% disappearance of atelectasis either complete or partial and finally Group III showed 64.29% disappearance of atelectasis either complete or partial. As regards changes in both FEV1% and FVC%; all patient groups showed significant differences pretreatment and one month after completion of treatment and Group I patients was significantly different than patients of both Groups II & III. ConclusionsThe replacement of external radiation with bronchoscopic therapy may not be a recommended option, but its addition to XRT may be a relatively simple method of augmenting the symptom palliative effect, providing higher response rates for re-expansion of collapsed lung and reducing endobronchial obstruction endoscopically.

Incidental Nodal Irradiation in Stage III Lung Cancer Treated With Involved-Field Radiation: Comparison Between 3DCRT and IMRT

o However, caution must be taken when delivering IFRT with IMRT if there is high risk for subclinical disease in the AP window nodal regions. Sonam Sharma, Jonathan Whaley, Jennifer Wei Zou, Annemarie Fernandes, Eric Xanthopoulos, Charles B. Simone II, John P. Christodouleas, Stefan Both, Ramesh Rengan, Smith Apisarnthanarax Incidental nodal irradiation in stage III lung cancer treated with involved field radiation: comparison between 3DCRT and IMRT

Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer

New therapeutic approaches are being developed based on findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) can influence chemosensitivity. The identification of molecular markers, useful for therapeutic decisions in lung cancer, is thus crucial for disease management. The present study evaluated single-nucleotide polymorphisms (SNPs) in XRCC3, XPD and Aurora kinase A in NSCLC patients in order to assess whether these biomarkers were able to predict the outcomes of the patients. The Spanish Lung Cancer Group prospectively assessed this clinical study. Eligible patients had histologically confirmed stage IV or IIIB (with malignant pleural effusion) NSCLC, which had not previously been treated with chemotherapy, and a World Health Organization performance status (PS) of 0-1. Patients received intravenous doses of vinorelbine 25 mg/m(2) on days 1 and 8, and cisplatin 75 mg/m(2) on day 1, every 21 days for a maximum of 6 cycles. Venous blood was collected from each, and genomic DNA was isolated. SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 were assessed. The study included 180 patients. Median age was 62 years; 87 % were male; 34 % had PS 0; and 83 % had stage IV disease. The median number of cycles was 4. Time to progression was 5.1 months (95 % CI, 4.2-5.9). Overall median survival was 8.6 months (95 % CI, 7.1-10.1). There was no significant association between SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 in outcome or toxicity. Our findings indicate that SNPs in XRCC3, XPD or Aurora kinase A cannot predict outcomes in advanced NSCLC patients treated with platinum-based chemotherapy.

1620 - Weight Loss Despite Oral Glutamine Supplementation Predicts Poor Prognosis in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy

ABSTRACT Background In this retrospective study, we investigated potential impact of weight change according to oral glutamine supplementation (GLT) on survival in patients with stage IIIB non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. Materials and methods Of the 142 patient evaluated retrospectively, 84 received GLT (GLT+), and 58 refused GLT intake (GLT-) and analyzed as control group. GLT was given at a daily dose of 30 g in powder form mixed with fruit juices. All patients received thoracic radiotherapy (TRT) to a total dose of 60-66 Gy (2Gy/Fx) concurrently with 2 cycles of cisplatin-based chemotherapy. Results During CRT, 76 (53.5) cases lost weight while remaining cases retained or gained weight. Weight loss in GLT- group (74.1%) was more frequent than GLT+ group (39.3%) (p Table 1 ) revealed cases in GLT+ group that retained or gained weight had the best outcome compared to the others. Bonferoni correction of two groups that retained of gained weight (p must be Table: 1620 Survival results according to glutamine supplementation (GLT) and wieght loss (WL) GLT- and KK+ GLT- and KK- GLT+ and KK+ GLT+ and KK- P-value Median OS Months) (95%CI) 15.7 (11.8-19.6) 21,7 (12.1-31.3) 13.5 (9.8-17.2) Not reached yet 1-year OS 65.1 93.3 60.6 98.0 2-year OS 12.1 44.9 3.8 58.3 Conclusion Results of this study demonstrated that GLT supplementation during CRT could prevent weight loss, yielding a better survival outcome in locally advanced NSCLC. Moreover, weight loss indicates poor prognosis irrespective of GLT use, and no long term survivors in GLT- group with weight loss suggests GLT resistance as a potentially poor prognostic factor, which warrants to be verified by further studies with larger cohorts. Disclosure All authors have declared no conflicts of interest.

1207P - Prognostic Factors in Development of Brain Metastasis in Stage III Non-Small Cell Lung Cancer Patients After Definitive Treatment

ABSTRACT Purpose To determine the incidence and prognostic factors of brain metastatsis in locally advanced non-small cell lung cancer (NSCLC) patients who were curatively treated. Materials and methods Curatively treated 136 patients with stage IIIA/ IIIB NSCLC between 1997-2011 were retrospectively reviewed. M/F: 112/24. Median age was 61 (36-82). Median Karnofsky Performance Scale was 80 (70-100). 61 patients (45%) were IIIA. Histology was adenocarcinoma in 27%, and squamous cell cancer in 54%. Seventy patients had concomitant or sequential chemoradiotherapy (CRT), 16% had radiotherapy (RT). All patients received platinum based chemotherapy. Median 60 Gy was administered with conformal RT. The ratio and time to brain metastasis were noted. Age, gender, stage, histology and surgery were examined as prognostic factors. Results Median follow-up was 13 months (range, 2-61 months). Two-year survival rate was 31%. One-year incidence of brain metastasis was 28.7%. In univariate analysis showed that patients younger than 60 years of age had more brain metastases than older patients (36% vs 15%, p = 0.01). Brain was more frequently the first site of metastases in younger patients than >60years (22% vs 9%, p > 0.05). Histology also significantly effected the development of brain metastasis (43.2% in adenocarcinoma, 16.4% in epidermoid carcinoma, p = 0.004). On multivariate analysis, only age was found to be significant prognostic factor (p = 0.01) Conclusion Age and histology significantly effects development of brain metastasis in locally advanced NSCLC. Younger age was the only significant variable for brain metastasis. Disclosure All authors have declared no conflicts of interest.

FOXP3+/CD8+ tumor-infiltrating T-cell ratio as a marker for pathologic response to induction therapy of non-small cell lung cancer.

e17517 Background: Survival benefits of induction therapy followed by surgery for advanced non-small cell lung cancer (NSCLC) have been shown. Anti-cancer agents are suggested to mediate cytotoxic effect not only directly on tumor cells but also through the immune system. We investigated the relationship between the status of T-cell differentiation in tumor stroma and pathologic responses to induction therapy in patients with advanced NSCLC. Methods: A total of 69 patients with c-stage IIA to IIIB NSCLC who underwent induction therapy followed by R0 surgery between January 2002 and July 2011 were enrolled. Tumor-infiltrating T cells expressing CD8 or FOXP3 were detected by immunohistochemical staining from biopsy and surgically removed specimens using anti-CD8 antibody and anti-FOXP3 antibody. Staining-positive T cells were counted in 10 fields at 200× magnification of digital images, and then FOXP3+/CD8+ T cell ratio was determined based on the average counts. Results: The mean values of FOXP3+/CD8+ T cell ratio in operative specimens were 1.11 for the patients with pathological no change (p-NC), 0.32 for those with pathological partial response (p-PR), and 0.21 for those with pathological complete response (p-CR) (p = 0.002). There was no association of FOXP3+/CD8+ T cell ratio with gender, histologic types of tumor, or clinical stages. Patients with p-CR showed better relapse-free survival, though statistically no-significant (p = 0.323). Pre-treatment TBLB specimens were available in 12 patients (3 p-NCs, 7 p-PRs, and 2 p-CRs). FOXP3+/CD8+ T cell ratios in operative specimens after induction therapies were elevated compared with that of biopsy specimens in p-NC patients (p = 0.105), whereas the ratios were decreased in p-PR and p-CR patients (p = 0.021). Conclusions: The status of tumor-infiltrating T cell differentiation indicated by FOXP3+/CD8+ T cell ratio was correlated with pathologic response in patients treated with induction therapy followed by surgery for NSCLC. FOXP3+/CD8+ T cell ratio can be a marker for effectiveness of induction treatment.

Novel Approaches of Chemoradiotherapy in Unresectable Stage IIIA and Stage IIIB Non-Small Cell Lung Cancer

Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.

Fludarabine combined with radiotherapy in patients with locally advanced NSCLC lung carcinoma: a phase I study

Background and purposeFludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation.Materials and methodsThirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m2 per day and increased by steps of 3 mg/m2 per day.ResultsAt a daily dose of 16 mg/m2, one out of six patients developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III toxicity was not observed. The dose of 13 mg/m2 was identified as the MTD. All patients developed a fludarabine dose-dependent lymphocytopenia.ConclusionFludarabine can be safely administered concurrently with radiation at a daily dose of 13 mg/m2 during the final 2 weeks of radiotherapy. Further prospective clinical studies are required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of locally advanced inoperable NSCLC.

Novel Approaches of Chemoradiotherapy in Unresectable Stage IIIA and Stage IIIB Non-Small Cell Lung Cancer

Novel Approaches of Chemoradiotherapy in Unresectable Stage IIIA and Stage IIIB Non-Small Cell Lung Cancer

Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non–Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens

To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

A Randomized Phase III Trial of Combined Paclitaxel, Carboplatin, and Radiation Therapy Followed by Weekly Paclitaxel or Observation for Patients With Locally Advanced Inoperable Non–Small-Cell Lung Cancer

BackgroundThis study was designed to determine the efficacy and safety of additional maintenance chemotherapy after standard induction chemotherapy/radiation therapy (XRT) in stage III non–small-cell lung cancer (NSCLC). The primary objective was to increase 1-year survival. Patients and MethodsEligible patients (N = 220) had confirmed stage IIIA or IIIB NSCLC, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients received induction chemotherapy (paclitaxel 200 mg/m2 + carboplatin AUC = 6/3 weeks) for 2 cycles, followed by paclitaxel 45 mg/m2 + carboplatin AUC = 2 weekly ×7 and concurrent daily XRT (cumulative dose = 66.6 Gy in 37 fractions) and then observation or maintenance. Before randomization, 101 patients (46%) discontinued treatment due to progressive disease (n = 34), toxicity (n = 33), patient request (n = 13), death (n = 7), or other (n = 14). The remaining 119 patients were randomly assigned to either “observation” or “maintenance” (6 cycles of paclitaxel 70 mg/m2/wk [3 weeks on/1 week off]); a median of 5 of 6 planned cycles was delivered in the maintenance arm. ResultsFor the observation group vs. the maintenance group, the estimated 1- and 4-year survival rates were 77% vs. 66% and 38% vs. 17% (median, 26.9 months vs. 16.1 months, respectively [P = .07]); the estimated 1- and 4-year performance-free survival (PFS) were 46% vs. 24% and 25% vs. 13% (median, 10.2 months vs. 8.2 months, respectively [P = .04]). Common toxicities were neutropenia, thrombocytopenia, and fatigue. ConclusionMedian survival in both groups surpassed the standard, most notably the 26.9-month survival in the observation group. Maintenance chemotherapy, when added to a regimen of both induction and concurrent chemoradiotherapy, did not improve clinical outcomes, with endpoints favoring the standard arm.

Consolidation chemotherapy following concurrent chemoradiation therapy for locally advanced inoperable non-small cell lung cancer

Concurrent chemoradiation therapy is currently a recommended treatment approach for locally advanced inoperable stage ⅢA and stage ⅢB non-small cell lung cancer (NSCLC).There is no consensus on the optimal treatment regimen.It is one of these options for the consolidation chemotherapy following concurrent chemoradiation therapy.To date,there is no sufficient evidence indicating that consolidation chemotherapy following concurrent chemoradiation therapy further improves survival rates.The benefit remains to be confirmed by more clinical test. Key words: Carcinoma, non-small-cell lung; Radiotherapy, adjuvant; Drug therapy, combination; Chemotherapy, adjuvant