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1.  A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Non-squamous Non-small Cell Lung Cancer 
Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.
Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m2 on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.
From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1– 42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8 –7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0 –16.5). The OS is 57% at 1 year and 10% at 2 years.
Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate.
PMCID: PMC4241413  PMID: 20881641
Lung cancer; Non-small cell; Antiangiogenic agents
2.  Quality of life after the initial treatments of non-small cell lung cancer: a persistent predictor for patients’ survival 
Health-related quality of life (HRQoL) before treatment may predict survival of patients with non-small-cell lung cancer (NSCLC). We investigated the predictive role of HRQoL after the initial treatments, on the survival of these patients.
A prospective multi-center study conducted in northeastern France. The SF-36 and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (QLQ C-30) were mailed to patients 3 months after the end of the diagnostic process. High scores for functioning dimensions on both questionnaires indicated better QoL, and low scores for symptom dimensions on the QLQ C-30 indicated few symptoms. Cox regression modeling was used to identify predictive factors of survival.
In total, 230 (63.5%) patients responded to the SF-36 and QLQ C-30. Before completing the questionnaires, almost 60% of patients had undergone some chemotherapy, about 10% underwent radio/chemotherapy or both and more than 30% underwent surgery or surgery plus chemo/radiotherapy.
On SF-36, the highest mean score was for social functioning dimension (55.5 ± 28), and the lowest was for the physical role dimension (17.9 ± 32.2).
On QLQ C-30, for the functioning dimensions, the highest mean score was for cognitive functioning (74.6 ± 25.9) and the lowest was for role functioning (47.2 ± 34.1). For symptom dimensions, the lowest score was for diarrhoea (11.5 ± 24.2) and the highest was for fatigue (59.7 ± 27.7).
On multivariate analysis, high bodily pain, social functioning and general health scores (SF-36) were associated with a lower risk of death (hazard ratio 0.580; 95% confidence interval [0.400–0.840], p = 0.004; HR 0.652 [0.455–0.935], p < 0.02; HR 0.625 [0.437–0.895] respectively). Better general QoL on QLQ C-30 was related to lower risk of death (HR 0.689 [0.501–0.946], p = 0.02).
Adding to previous knowledge about factors that may influence patients QoL, this study shows a persisting relationship between better perceived health in HRQoL after the initial treatment of NSCLC and better survival.
PMCID: PMC4026822  PMID: 24884836
Quality of Life; SF-36; QLQ C-30; Non-small-cell lung cancer; Survival
3.  Survival following non-small cell lung cancer among Asian/Pacific Islander, Latina, and non-Hispanic White women who have never smoked 
Lung cancer is the leading cause of cancer death among US Asian/Pacific Islander (API) and Latina women, despite low smoking prevalence. This study examined survival patterns following non-small cell lung cancer in a population-based sample of lung cancer cases from the San Francisco Bay Area Lung Cancer Study (SFBALCS).
Women diagnosed with lung cancer from 1998–2003 and 2005–2008 and identified through the Greater Bay Area Cancer Registry were telephone-screened for eligibility for the SFBALCS. The screener data were linked to the cancer registry data to determine follow-up. This analysis included 187 non-Hispanic White, 23 US-born Latina, 32 foreign-born Latina, 30 US-born API, and 190 foreign-born API never smokers diagnosed with lung cancer and followed through 2008.
All-cause survival was poorer among APIs (hazard ratio (HR) and 95% confidence interval (CI) = 1.7 (1.0–2.8) among US-born APIs; 1.2 (0.9–1.5) among foreign-born APIs), and Latinas (HR (95% CI) = 2.1 (1.2–3.6) among US-born Latinas; 1.4 (0.9–2.3) among foreign-born Latinas), relative to non-Hispanic Whites. These survival differences were not explained by differences in selected sociodemographic or clinical factors.
Further research should focus on factors such as cultural behaviors, access to or attitudes toward health care, and genetic variations, as possible explanations for these striking racial/ethnic differences.
Latina and API female never smokers diagnosed with lung cancer were up to two-times more likely to die than non-Hispanic Whites, highlighting the need for additional research to identify the underlying reasons for the disparities, as well as heightened clinical awareness.
PMCID: PMC3070404  PMID: 21239685
lung cancer survival; Asian; Latina; Hispanic; never smokers; nativity
4.  How Accurate Are Physicians in the Prediction of Patient Survival in Advanced Lung Cancer? 
The Oncologist  2010;15(7):782-789.
The study compared actual with predicted survival estimates in advanced stage non-small cell lung cancer patients. Regardless of years of experience, physicians overestimated the survival duration of these patients.
Because most cases of non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage with a poor prognosis, patient inclusion in clinical trials is critical. Most trials require an estimated life expectancy >3 months, based on clinician estimates of patient survival probability, without providing formal guidelines. The aim of this study was to assess the accuracy of clinicians' predictions of survival in NSCLC patients (stages IIIB, and IV) and the possible impact of patient quality of life on survival estimation.
At diagnosis, clinical, biological, and quality of life data (QLQ-C30 questionnaire) were recorded, and doctors “forecast” each patient's estimated survival. Concordance between predicted and actual survival was assessed with the intraclass correlation coefficient.
Eighty-five patients with a mean age of 62.2 years, 81.1% male, were included (squamous cell carcinoma, 33; adenocarcinoma, 42; large cell carcinoma, 8; neuroendocrine carcinoma, 2). The mean follow-up was 40 months and median survival time was 11.7 (range, 0.4–143.7) weeks. All clinicians (residents, registrars, and consultants) overestimated patient survival time, with a moderate concordance between predicted and actual survival time. A worse global health status was associated with a lower discrepancy between estimated and actual patient survival, and a worse role functioning was associated with a larger difference between estimated and actual patient survival.
The absence of specific recommendations to estimate patient survival may introduce major selection in clinical studies. Further research should investigate whether the accuracy of patient survival estimates by clinicians would be improved by taking into account patient quality of life.
PMCID: PMC3228014  PMID: 20558582
Advanced stage non-small cell lung cancer; Survival; Quality of life; Prognostic factors; Predictive estimation

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