Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer.

BACKGROUND: Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. Insights into mechanisms of resistance to selective RET inhibitors remain limited. PATIENTS AND METHODS: This study was performed at five institutions. Tissue and/or cell-free DNA was obtained from patients with RET fusion-positive NSCLC after treatment with selpercatinib or pralsetinib and assessed by next-generation sequencing (NGS) or MET FISH. RESULTS: We analyzed a total of 23 post-treatment tissue and/or plasma biopsies from 18 RET fusion-positive patients who received an RET-selective inhibitor (selpercatinib, n = 10; pralsetinib, n = 7; pralsetinib followed by selpercatinib, n = 1, with biopsy after each inhibitor). Three cases had paired tissue and plasma samples, of which one also had two serial resistant tissue specimens. The median progression-free survival on RET inhibitors was 6.3 months [95% confidence interval 3.6-10.8 months]. Acquired RET mutations were identified in two cases (10%), both affecting the RET G810 residue in the kinase solvent front. Three resistant cases (15%) harbored acquired MET amplification without concurrent RET resistance mutations, and one specimen had acquired KRAS amplification. No other canonical driver alterations were identified by NGS. Among 16 resistant tumor specimens, none had evidence of squamous or small-cell histologic transformation. CONCLUSIONS: RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.

Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study.

BACKGROUND: The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019). PATIENTS AND METHODS: Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety. RESULTS: Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32-0.58; median PFS 34.8 versus 10.9 months crizotinib]. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46-0.98). The 5-year OS rate was 62.5% (95% CI 54.3-70.8) with alectinib and 45.5% (95% CI 33.6-57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline [HR 0.58 (95% CI 0.34-1.00)] and those without [HR 0.76 (95% CI 0.45-1.26)]. Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed. CONCLUSIONS: Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC. CLINICAL TRIALS NUMBER: NCT02075840.

Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001.

BACKGROUND: In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001. PATIENTS AND METHODS: ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily. RESULTS: Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2-45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2-39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment. CONCLUSIONS: These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT00585195.

Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib.

Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic.

Safety of alectinib for the treatment of metastatic ALK-rearranged non-small cell lung cancer.

INTRODUCTION: Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) may derive significant clinical benefit from targeted therapies against this driver mutation, but progression is virtually inevitable. Alectinib is a next-generation ALK inhibitor that provides a novel treatment option for this group of patients. Areas covered: In this review, we summarize the overall safety and tolerability of alectinib. Specifically, we cover cardiovascular, gastrointestinal, hepatic, musculoskeletal, and respiratory adverse events. The safety profile of alectinib is also described in special populations and in comparison with other ALK inhibitors. Expert opinion: Alectinib is a well-tolerated tyrosine kinase inhibitor and should be considered for patients with ALK-rearranged NSCLC. The question then arises as to how to choose a next-generation ALK inhibitor in the second-line setting. Understanding acquired resistant mechanisms has become essential. Whether or not to use alectinib in the first-line setting is extremely controversial, but we anticipate its approval for this indication and availability in more countries in the near future.

[Prognostic analysis of acute-on-chronic liver failure after withdrawal of nucleos(t)ide analogues for antiviral treatment of chronic hepatitis B].

OBJECTIVE: To investigate the prognostic factors for acute-on-chronic liver failure (ACLF) after the withdrawal of nucleos(t)ide analogues (NAs) for the antiviral treatment of chronic hepatitis B (CHB). METHODS: The clinical data of 67 hospitalized patients with ACLF after withdrawal of NAs for the antiviral treatment of CHB were analyzed retrospectively. RESULTS: The HBeAg status before initial treatment and after recurrence, course of the antiviral treatment, duration from the withdrawal of NAs to recurrence, and type of NAs before and after withdrawal were not associated with the prognosis of ACLF. The Cox univariate regression analysis showed that serum bilirubin, international normalization ratio, serum creatinine, model of end-stage of liver disease (MELD) score, hepatic encephalopathy, and concurrent infection were associated with the 12-week death. The Cox multivariate regression analysis showed that MELD score and hepatic encephalopathy were independent predictors for 12-week death. The area under the receiver operating characteristic curve for the MELD score to predict 12-week death was 0.906, with an optimal cutoff value of 32, a sensitivity of 82.9%, a specificity of 88.5%, a positive predictive value of 91.9%, and a negative predictive value of 76.7%. CONCLUSION: MELD score and hepatic encephalopathy are closely associated with the prognosis of patients with ACLF after withdrawal of NAs for the antiviral treatment of CHB.

What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC).

BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion. PATIENTS AND METHODS: This alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions. RESULTS: A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays. CONCLUSIONS: This first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810).

Innovative personalized medicine in gastric cancer: time to move forward.

Globally, gastric cancer (GC) is the second leading cancer cause of death. To date, only one targeted therapy trial generated positive survival outcomes in a selected population among many targeted therapy trials. This trial showed the addition of trastuzumab to fluoropyrimidine/platinum chemotherapy as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive GC that resulted in an overall survival (OS) benefit. The increasing use of next generation sequencing approach to genomically profile GC patients allows the identification of many more GC patients who could benefit from specific targeted agents. Here we provide a comprehensive review of targeted therapy trials in GC and discuss future potential actionable driver mutations in GC.

Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC.

BACKGROUND: Crizotinib is approved to treat advanced ALK-positive non-small-cell lung cancer (NSCLC), but most patients ultimately develop progressive disease (PD). We investigated whether continuing ALK inhibition with crizotinib beyond PD (CBPD) is clinically beneficial and attempted to identify clinicopathologic characteristics associated with patients who experience clinical benefit. PATIENTS AND METHODS: Patients with advanced ALK-positive NSCLC enrolled in two ongoing multicenter, single-arm trials who developed RECIST-defined PD were allowed to continue crizotinib if they were deriving ongoing clinical benefit. In the present retrospective analysis, continuation of CBPD was defined as >3 weeks of crizotinib treatment after PD documentation. Patients who had PD as best response to initial crizotinib treatment were excluded. Baseline and post-progression characteristics, sites of PD, and overall survival (OS) were compared in patients who continued CBPD versus those who did not. The impact of continuing CBPD on OS after adjusting for potential confounding factors was assessed. RESULTS: Among 194 crizotinib-treated patients with RECIST-defined PD, 120 (62%) continued CBPD. A significantly higher proportion of patients who continued CBPD than patients who did not had an ECOG performance status (PS) of 0/1 at PD (96% versus 82%; P=0.02). CBPD patients had significantly longer OS from the time of PD [median 16.4 versus 3.9 months; hazards ratio (HR) 0.27, 95% confidence interval (CI): 0.17-0.42; P<0.0001] and from the time of initial crizotinib treatment (median 29.6 versus 10.8 months; HR 0.30, 95% CI: 0.19-0.46; P<0.0001). The multiple-covariate Cox regression analysis revealed that CBPD remained significantly associated with improved OS after adjusting for relevant factors. CONCLUSIONS: Patients who continued CBPD were more likely to have good ECOG PS (0/1) at the time of PD. Continuing ALK inhibition with crizotinib after PD may provide survival benefit to patients with advanced ALK-positive NSCLC.

The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma.

BACKGROUND: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. PATIENTS AND METHODS: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. RESULTS: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). CONCLUSIONS: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study.

PURPOSE: This phase II study evaluated efficacy and safety of single-agent axitinib, an oral, potent, selective inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received a starting dose of axitinib 5 mg orally BID. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response rate. Secondary end points included safety and tolerability, overall survival (OS), and progression-free survival (PFS). RESULTS: Thirty-two patients were enrolled, with a median age of 66.5 years. The majority of patients (75%) had adenocarcinoma. Nine patients (28%) had received no prior chemotherapy for metastatic disease, and 23 (72%) had received > or = one regimen. Three patients (9%) had a RECIST investigator-assessed, confirmed partial response (PR); disease control rate (PR + stable disease) was 41%. Median PFS was 4.9 months overall (95% CI, 3.6 to 7.0 months). Median OS was 14.8 months (95% CI, 10.7 months to not estimable) overall and 14.8 months (95% CI, 12.5 months to not estimable) in patients receiving first-line axitinib. One-year survival rates for patients with or without prior therapy for metastatic disease were 57% and 78%, respectively. Grade 3 treatment-related adverse events in > or = 5% of patients comprised fatigue (22%), hypertension (9%), and hyponatremia (9%). CONCLUSION: Axitinib demonstrated single-agent activity in patients with advanced NSCLC. Therapy was well tolerated with manageable toxicities. Further investigation of this VEGFR inhibitor in NSCLC is of interest.

Low socioeconomic status is a poor prognostic factor for survival in stage I nonsmall cell lung cancer and is independent of surgical treatment, race, and marital status.

BACKGROUND: Racial minorities exhibit poor survival with nonsmall cell lung cancer (NSCLC) that generally is attributed to low socioeconomic status (SES). In this study, the authors investigated the role of SES in this survival disparity among patients with stage I NSCLC. METHODS: A case-only analysis was performed on California Cancer Registry (CCR) data (1989-2003). Univariate survival analyses were performed using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: In total, 19,702 incident cases of stage I NSCLC were analyzed. Low SES was identified more commonly in African-American and Hispanic patients and was associated significantly with men, unmarried status, stage IB disease, squamous cell histology, poorly differentiated tumors, fewer surgical resections performed, and less overall treatment received. Reasons for no surgery were associated strongly with low SES and unmarried status but not with race. In multivariate analysis, each incremental improvement in SES quintile was associated with statistically significant decreases in the hazard ratios (HRs) for death (second SES quintile [SES2] vs SES1: HR, 0.91; 95% confidence interval [95% CI], 0.85-0.98; SES3 vs SES1: HR, 0.90; 95% CI, 0.84-0.97; SES4 vs SES1: HR, 0.83; 95% CI, 0.77-0.89; SES5 vs SES1: HR, 0.78; 95% CI, 0.72-0.84; P(trend) < .0001). African-American or Hispanic race was not an independent poor prognostic factor for survival after adjustment for surgery, SES, and marital status. CONCLUSIONS: Low SES was an independent poor prognostic factor for survival in patients with stage I NSCLC and was independent of surgery, race, and marital status.

Survival improvements for advanced stage nonbronchioloalveolar carcinoma-type nonsmall cell lung cancer cases with ipsilateral intrapulmonary nodules.

BACKGROUND: Survival improvements have been demonstrated for patients with bronchioloalveolar (BAC) nonsmall cell lung cancer (NSCLC) with intrapulmonary satellite T4 nodules compared with other patients with stage IIIB disease, and for ipsilateral intrapulmonary M1 tumors versus contralateral or distant metastasis. However, it is not known whether these differences are observed in patients with non-BAC NSCLC. METHODS: A case-only analysis of the U.S. Surveillance, Epidemiology, and End Results (SEER) data (1999-2003) was conducted. Overall survival (OS) and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: A total of 27,435 incident cases of histologically confirmed, advanced stage NSCLC were identified. Cases with stage IIIB NSCLC due to multiple lesions in the same lobe (n = 633) had a significantly improved median OS (21 months) and LCSS (31 months) compared with other cases with stage IIIB NSCLC (n = 7695), with an OS of 7 months and an LCSS of 9 months (P < .0001 for both comparisons). Among cases with stage IV NSCLC, those with intrapulmonary nodules (n = 3010) had a significantly improved median OS (9 months) and LCSS (10 months) compared with those with distant metastasis (n = 16,097), with an OS of 4 months and an LCSS of 5 months (P < .0001 for both comparisons). These survival differences persisted after adjustment for age, sex, ethnicity, surgery, and radiotherapy. Among cases with stage IV NSCLC, those with ipsilateral intrapulmonary nodules (n = 1120) had improved OS (12 months) compared with those with bilateral intrapulmonary nodules (n = 1890), with an OS of 7 months (P < .0001). CONCLUSIONS: Cases with stage IIIB and IV NSCLC with ipsilateral intrapulmonary nodules were found to have improved survival outcomes compared with other cases with stage IIIB and IV disease. The results of the current study add additional support for modifications to the current NSCLC staging system.

Validation of the proposed International Association for the Study of Lung Cancer non-small cell lung cancer staging system revisions for advanced bronchioloalveolar carcinoma using data from the California Cancer Registry.

BACKGROUND: Recently, the International Association for the Study of Lung Cancer (IASLC) has proposed significant modifications to the existing TNM and stage grouping classifications affecting the T4 and M descriptors. We set out to validate this staging system for bronchioloalveolar carcinoma (BAC) cases using data from the California Cancer Registry (CCR). METHODS: We identified 1909 patients from the CCR between 1999 and 2003 with histologically confirmed BAC and complete TNM staging and reclassified them according to the IASLC proposed staging revisions. There were 657 patients with stage IIIB and IV disease who formed the primary analysis of the changes to T4 and M descriptors. Surveillance Epidemiology and End Results (SEER) extent of disease codes (EOD) were used to identify various T4 and M descriptors. The primary outcome measured was overall survival (OS) for stage-specific comparisons of the existing to the proposed staging systems, using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: Using the proposed criteria, 162 (25%) of the 657 patients with advanced BAC were reclassified: 73 patients with multiple lesions in the same lobe as T3 (stage II T3N0M0 [n = 53], stage IIIA T3N1-2M0 [n = 18], stage IIIB T3N3M0 [n = 1] or T3NXM0 [n = 1]); 89 patients with ipsilateral intrapulmonary metastasis were reclassified as T4 (stage IIIA T4N0-N1M0 [n = 54], stage IIIB T4N2-3M0 [n = 23] or T4NXM0 [n = 12]). Univariate and multivariate survival analysis of this validation set revealed an improved fit for the proposed IASLC staging system compared with the existing staging system. CONCLUSIONS: The proposed IASLC staging system modifications accurately reflect survival characteristics for BAC and represent an improvement compared with the existing staging system.

Performance and microbial diversity of a membrane bioreactor treating real textile dyeing wastewater.

The textile industry is one of the major industries of Taiwan but unfortunately it produces toxic and low biodegradable wastewater. To remedy this problem, this study compared the performance of the membrane bioreactor (MBR) and sequencing batch reactor (SBR) processes for treating real textile dyeing wastewater. The microbial diversity of the MBR process was also identified by a combination of culturing methods and molecular biotechnology. The removal efficiencies of the MBR process for color, COD, BOD, and SS were 54, 79, 99, and 100%, respectively, all higher than the corresponding parameters for the SBR process: i.e., 51, 70, 96, and 60%. All the above four parameters for the MBR effluent meet the criteria of the Taiwan EPA, while on the other hand, for the SBR process, only color and COD meet the Taiwan EPA effluent criteria. Furthermore, the genus Microbacterium, in particular Microbacterium aurum, was the most predominant population, accounting for 70.6% of the total isolates, and might be responsible for the degradation of the dyeing wastewater. Another two textile dyeing degradation bacteria, Paenibacillus azoreducens and Bacillus sp., were also observed as predominant bacteria in MBR sludge.

Burkitt's lymphoma of the base of the tongue: a case report and review of the literature.

Burkitt's lymphoma is a highly aggressive, mature B cell non-Hodgkin's lymphoma that is rare outside Africa. We report a case of Burkitt's lymphoma presenting as a rapidly expanding tongue-base mass that caused airway obstruction in an 80-year-old Palestinian man living in California. According to our review of the literature, this is only the third reported case of Burkitt's lymphoma arising in the base of the tongue. We also discuss the incidence, epidemiology, genetics, prognosis, and treatment of this malignancy. Because Burkitt's lymphoma is one of the fastest-growing tumors in humans, rapid diagnosis and treatment are important. Treatment involves brief-duration, high-intensity chemotherapy and central nervous system prophylaxis. It is important for the otolaryngologist to recognize this disease and to understand the steps necessary to treat this aggressive tumor.

Prognostic factors for survival of stage I nonsmall cell lung cancer patients : a population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003.

BACKGROUND: Platinum-based adjuvant chemotherapy in randomized trials has failed to provide a survival benefit in patients with resected stage I nonsmall cell lung cancer (NSCLC). Using data from the California Cancer Registry (CCR), we explored factors that had detrimental effects on survival in patients with stage I NSCLC to identify a subset of patients at high risk for disease recurrence and subsequent mortality. METHODS: Between 1989 and 2003, 19,702 incident cases of stage I NSCLC in the CCR were identified and subgrouped into stage IA and IB disease. Patient demographic factors, tumor characteristics, and treatment delivered were examined. Kaplan-Meier survival curves were calculated to estimate survival rates. Cox proportional-hazards ratios were used to identify independent prognostic factors for survival. RESULTS: Advanced age at diagnosis, male sex, low socioeconomic status (SES), nonsurgical treatment, and poor histologic grade (stage IA NSCLC: hazards ratio [HR], 1.13; 95% confidence interval [95% CI], 1.08-1.19; stage IB NSCLC: HR, 1.11; 95% CI, 1.07-1.16) were associated with increased mortality risk on multivariate analysis. Non-upper lobe tumor location (right middle lobe, right and left lower lobes) and tumor size > or =4 cm (vs <4 cm: HR, 1.23; 95% CI, 1.15-1.30) were additional factors that increased the risk of mortality among patients with stage IB disease. Bronchioloalveolar carcinoma and Asian ethnicity were associated with decreased mortality risk in stage I NSCLC. CONCLUSIONS: Stage I NSCLC with poorly differentiated histology and stage IB NSCLC with non-upper lobar tumor location or tumor size > or =4 cm carried an increased mortality risk.