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ABSTRACT: Small cell lung cancer (SCLC) is a lethal disease for which there have been only small advances in diagnosis and treatment in the past decade. Our goal was to revise the evidence-based guidelines on staging and best available treatment options.
A comprehensive literature search covering 2004 to 2011 was conducted in MEDLINE, Embase, and five Cochrane databases using SCLC terms. This was cross-checked with the authors' own literature searches and knowledge of the literature. Results were limited to research in humans and articles written in English.
The staging classification should include both the old Veterans Administration staging classification of limited stage (LS) and extensive stage (ES), as well as the new seventh edition American Joint Committee on Cancer/International Union Against Cancer staging by TNM. The use of PET scanning is likely to improve the accuracy of staging. Surgery is indicated for carefully selected stage I SCLC. LS disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle 1 or 2 of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. ES disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in those individuals with both LS and ES disease who achieve a complete or partial response to initial therapy. To date, no molecularly targeted therapy agent has demonstrated proven efficacy against SCLC.
Evidence-based guidelines are provided for the staging and treatment of SCLC. LS-SCLC is treated with curative intent with 20% to 25% 5-year survival. ES-SCLC is initially responsive to standard treatment, but almost always relapses, with virtually no patients surviving for 5 years. Targeted therapies have no proven efficacy against SCLC.
Chest 05/2013; 143(5 Suppl):e400S-19S. · 5.25 Impact Factor
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Thanyanan Reungwetwattana,
Julian R Molina,
Sumithra J Mandrekar,
Katie Allen-Ziegler,
Kendrith M Rowland,
Nicholas F Reuter,
Ronnie F Luyun,
Grace K Dy,
Randolph S Marks,
Steven E Schild, James R Jett,
Alex A Adjei
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ABSTRACT: In an effort to evaluate the single agent activity of temsirolimus in previously untreated non-small-cell lung cancer, the North Central Cancer Treatment Group undertook a frontline "window-of-opportunity" study.
Patients received 25 mg of temsirolimus administered intravenously as a weekly 30 minute infusion, on a 4-week cycle. Based on a two-stage Fleming design, the treatment would be promising if at least four of the first 25 evaluable patients in stage I or at least six of the 50 evaluable patients at the end of stage II have a confirmed response. Fresh tumor biopsies were obtained to evaluate predictive markers of temsirolimus activity.
A total of 55 patients were enrolled with 52 patients being evaluable. The median age was 64 years. Adverse events (grade 3/4) occurring in 33 patients included dyspnea (12%), fatigue (10%), hyperglycemia (8%), hypoxia (8%), nausea (8%), and rash/desquamation (6%). The clinical benefit rate was 35% with four patients achieving a confirmed partial response and 14 patients with stable disease for 8 weeks or more. The 24-week progression-free survival rate was 25%. Median progression-free survival and overall survival were 2.3 and 6.6 months, respectively. Expression of p70s6 kinase, phospho-p70s6 kinase, Akt, phospho-Akt, and phosphatase and tensin homolog mutation did not correlate with clinical outcome.
Temsirolimus given as a single agent in frontline therapy in patients with non-small-cell lung cancer was tolerable and demonstrated clinical benefit but did not meet the primary objective in this study. Patient selection will be needed to enhance the efficacy.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2012; 7(5):919-22. · 4.55 Impact Factor
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ABSTRACT: Screening for lung cancer is not currently recommended, even in persons at high risk for this condition. Most patients with lung cancer present with symptomatic disease that is usually at an incurable, advanced stage. The recently reported NLST (National Lung Screening Trial) showed a 20% decrease in deaths from lung cancer in high-risk persons undergoing screening with low-dose computed tomography of the chest compared with chest radiography. The high-risk group included in the trial comprised asymptomatic persons aged 55 to 74 years, with smoking history of at least 30 pack-years. Screening with low-dose computed tomography detected more cases of early-stage lung cancer and fewer cases of advanced-stage cancer, confirming that screening has shifted the stage of cancer at diagnosis and provides more persons with the opportunity for curative treatment. Although computed tomography screening has risks and limitations, the 20% decrease in deaths is the single most dramatic decrease ever reported for deaths from lung cancer, with the possible exception of smoking cessation. Physicians should offer computed tomography screening for lung cancer to patients who fit the high-risk profile defined in the NLST.
Annals of internal medicine 09/2011; 155(8):540-2. · 16.73 Impact Factor
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ABSTRACT: The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS.
Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ).
Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48).
PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials.
Cancer 10/2010; 117(6):1262-71. · 4.77 Impact Factor
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Cheng E. Chee MD,
James R. Jett MD,
Albert M. Bernath Jr MD,
Nathan R. Foster MS,
Garth D. Nelson MS,
MD Julian Molina PhD,
Daniel A. Nikcevich MD,
Preston D. Steen MD,
Patrick J. Flynn MD,
Kendrith M. Rowland Jr MD,
Cheng E. Chee, James R. Jett,
Albert M. Bernath Jr,
Nathan R. Foster,
Garth D. Nelson,
Julian Molina,
Daniel A. Nikcevich,
Preston D. Steen,
Patrick J. Flynn,
Kendrith M. Rowland Jr
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ABSTRACT: BACKGROUND:In extensive-stage small cell lung cancer (SCLC), the combination of pemetrexed plus carboplatin has shown activity and appeared to be well-tolerated. We conducted a trial to confirm the efficacy and to assess the tolerability of this chemotherapy combination.METHODS:Patients with untreated extensive-stage SCLC were enrolled in this phase 2 open-labeled study. They receive pemetrexed 500 mg/m2 and carboplatin (area under the curve of 5) every 21 days for a maximum 6 cycles. The primary endpoint for this trial was the confirmed response rate and the accrual goal was 70 patients.RESULTS:Forty-six eligible patients (29 aged <70 years, 17 aged ≥70 years) were accrued to this study. The efficacy outcomes were similar between the 2 age groups. Overall, the confirmed response rate was 35% (16 of 46; 95% confidence interval [CI], 21%-50%), where all 16 were partial responses. On the basis of these results, we had strong evidence that the study would not meet the preset efficacy criteria and was, therefore, closed before full accrual. The median duration of response was 4.4 months (95% CI, 2.9-5.2). Median overall survival for patients aged <70 years and aged ≥70 years was 9.2 months (95% CI, 5.4-11.6) and 10.8 months (95% CI, 2.2-14.3), respectively. Grade 3 or higher toxicity rates were similar between the younger and older patients. Grade 3/4 and grade 4 hematological toxicities were observed in 46% and 26% of patients, respectively.CONCLUSIONS:Although well-tolerated, the combination of pemetrexed and carboplatin is not as effective as standard therapy in patients with untreated extensive-stage SCLC. Cancer 2010. © 2010 American Cancer Society.
Cancer 05/2010; 116(10):2382 - 2389. · 4.77 Impact Factor
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ABSTRACT: Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history, but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric CT scan analysis.
Sixty-four cases of lung cancer were identified from a prospective cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial. Each case was matched to six control subjects for age, sex, and smoking history. Quantitative CT scan analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects.
Decreased FEV(1) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 (95% CI, 1.00-1.32; P = .046) and 1.29 (95% CI, 1.02-1.62; P = .031), respectively. The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 (95% CI, 0.816-1.329; P = .743). Additionally, there was no significant association between severe emphysema and lung cancer with OR of 1.57 (95% CI, 0.73-3.37).
We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic evidence of emphysema quantitation methodology, or absence of any relationship between emphysema and lung cancer risk.
Chest 03/2010; 138(6):1295-302. · 5.25 Impact Factor
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ABSTRACT: In extensive-stage small cell lung cancer (SCLC), the combination of pemetrexed plus carboplatin has shown activity and appeared to be well-tolerated. We conducted a trial to confirm the efficacy and to assess the tolerability of this chemotherapy combination.
Patients with untreated extensive-stage SCLC were enrolled in this phase 2 open-labeled study. They receive pemetrexed 500 mg/m(2) and carboplatin (area under the curve of 5) every 21 days for a maximum 6 cycles. The primary endpoint for this trial was the confirmed response rate and the accrual goal was 70 patients.
Forty-six eligible patients (29 aged <70 years, 17 aged >or=70 years) were accrued to this study. The efficacy outcomes were similar between the 2 age groups. Overall, the confirmed response rate was 35% (16 of 46; 95% confidence interval [CI], 21%-50%), where all 16 were partial responses. On the basis of these results, we had strong evidence that the study would not meet the preset efficacy criteria and was, therefore, closed before full accrual. The median duration of response was 4.4 months (95% CI, 2.9-5.2). Median overall survival for patients aged <70 years and aged >or=70 years was 9.2 months (95% CI, 5.4-11.6) and 10.8 months (95% CI, 2.2-14.3), respectively. Grade 3 or higher toxicity rates were similar between the younger and older patients. Grade 3/4 and grade 4 hematological toxicities were observed in 46% and 26% of patients, respectively.
Although well-tolerated, the combination of pemetrexed and carboplatin is not as effective as standard therapy in patients with untreated extensive-stage SCLC.
Cancer 03/2010; 116(10):2382-9. · 4.77 Impact Factor
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ABSTRACT: Considerable advances in genomics, transcriptomics and proteomics have in the recent years transformed our understanding of the molecular mechanisms involved in the pathogenesis of lung cancer and are in the process of revolutionizing our approach to its diagnosis and treatment. Although these techniques have traditionally been described in the context of large volume biopsies from surgically resected tumors, significant technical advances allow their application to smaller samples obtained bronchoscopically, often the only samples available in advanced lung cancer.
Recent data support the use of advanced molecular techniques as an adjunct to conventional histologic examinations of bronchoscopy specimens in the following situations: early diagnosis and screening of nonsmall cell lung cancer by fluorescent in-situ hybridization techniques in particular; accurate histologic diagnosis via novel immunohistochemistry markers; and prognosis and prediction of response to targeted and conventional chemotherapeutic agents.
Molecular biology techniques are increasingly applied to smaller biopsy specimens obtained via bronchoscopy, allowing for their use in advanced, unresectable nonsmall cell lung cancer. Although these techniques have not yet entered the clinical practice arena, they will likely become an unavoidable complement to conventional morphologic examinations and allow for individualized diagnostic and therapeutic approach to lung-cancer patients.
Current opinion in pulmonary medicine 02/2010; 16(4):315-20. · 3.08 Impact Factor
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ABSTRACT: Bronchoscopically collected cytology specimens are commonly used to obtain a diagnosis of cancer in patients with pulmonary lesions. However, the sensitivity of cytology is suboptimal, especially for peripheral lesions less than 2 cm in diameter.
We assessed the performance of a testing algorithm using cytology and fluorescence in situ hybridization (FISH) as part of clinical practice.
Bronchial brushing specimens (n = 343) were obtained from patients undergoing bronchoscopy for indeterminate pulmonary lesions. Routine cytology was performed and specimens without a positive diagnosis (n = 294) were analyzed by FISH, using residual brushing material. Pathology-confirmed lung cancer or clinical/radiographic evidence of disease was considered diagnostic of malignancy.
Routine cytology had a sensitivity and specificity of 41% (23 of 56) and 100% (45 of 45) for central lesions and 20% (26 of 133) and 100% (109 of 109) for peripheral nodules, respectively. FISH detected an additional 32% of lung cancers (18 central and 43 peripheral) not detectable by cytology alone, while producing false positive diagnoses in 22% (10 of 45) and 6% (6 of 109) benign central and peripheral lesions, respectively. In peripheral nodules, FISH detected (relative to routine cytology) an additional 44% (15 of 34) and 28% (25 of 91) of lung cancers less than 2 cm and 2 cm or more in size, respectively. A positive FISH result had a likelihood ratio of 1.45 and 5.87 for central and peripheral lesions and 3.44 and 15.38 for peripheral nodules less than 2 cm and 2 cm or more in size, respectively.
FISH testing significantly increases the detection of lung cancer over routine cytology alone. It is especially useful for peripheral nodules.
American Journal of Respiratory and Critical Care Medicine 12/2009; 181(5):478-85. · 11.08 Impact Factor
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ABSTRACT: Although no study has prospectively documented the rate at which lung cancers grow, many have assumed exponential growth. The purpose of this study was to document the growth of lung cancers detected in high-risk participants receiving annual screening chest CT scans.
Eighteen lung cancers were evaluated by at least four serial CT scans (4 men, 14 women; age range, 53 to 79 years; mean age, 66 years). CT scans were retrospectively reviewed for appearance, size, and volume (volume [v] = pi/6[ab(2)]). Growth curves (x = time [in days]; y = volume [cubic millimeters]) were plotted and subcategorized by histology, CT scan attenuation, stage, survival, and initial size.
Inclusion criteria favored smaller, less aggressive cancers. Growth curves varied, even when subcategorized by histology, CT scan attenuation, stage, survival, or initial size. Cancers associated with higher stages, mortality, or recurrence showed fairly steady growth or accelerated growth compared with earlier growth, although these growth patterns also were seen in lesser-stage lung cancers. Most lung cancers enlarged at fairly steady increments, but several demonstrated fairly flat growth curves, and others demonstrated periods of accelerated growth.
This study is the first to plot individual lung cancer growth curves. Although parameters favored smaller, less aggressive cancers in women, it showed that lung cancers are not limited to exponential growth. Tumor size at one point or growth between two points did not appear to predict future growth. Studies and equations assuming exponential growth may potentially misrepresent an indeterminate nodule or the aggressiveness of a lung cancer.
Chest 08/2009; 136(6):1586-95. · 5.25 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) is a primary malignancy characterized by local invasion of the pleura and metastasis. Despite advances in computed tomography (CT) and magnetic resonance imaging (MRI), accurately staging patients remains challenging. Recent studies have examined the use of integrated CT-positron emission tomography (PET) for staging patients.
Mayo Clinic databases were queried to identify cases with a histologic diagnosis of MPM from 2000 to 2006. Inclusion criteria were a diagnosis of MPM, an available CT scan, and an initial staging integrated CT-PET scan. A total of 35 patients were identified who met the inclusion criteria. Computed tomography and integrated CT-PET scans were reviewed by experienced radiologists. Laboratory parameters were reviewed. The Mayo Clinic tumor registry and Social Security database were queried for survival data in patients in which no follow-up was available.
Findings on integrated CT-PET excluded 14 of 35 patients from surgical intervention. Extrapleural pneumonectomies (EPPs) were performed in 8 patients, and partial pleurectomies were performed in 2 patients. Upstaging from integrated CT-PET occurred in 70% of the patients when surgical pathology was available, 2 cases to an inoperable stage. Although not statistically significant, median survival was 20 months for patients undergoing an EPP and 12 months for patients excluded from surgical intervention by integrated CT-PET.
Malignant pleural mesothelioma is a difficult disease to accurately stage. The most common reason for upstaging in our series was an increase in T (tumor; tumor-node-metastasis staging system) disease. Our data suggest that integrated CT-PET is excellent for detecting nodal and distant metastases. However, the ability of this imaging modality to correctly stage locoregional disease is not superior to the combination of CT and MRI as reported in the literature.
Clinical Lung Cancer 08/2009; 10(4):244-8. · 2.94 Impact Factor
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Thorax 06/2009; 64(5):371-2. · 6.84 Impact Factor
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Ping Yang,
Sumithra J Mandrekar,
Shauna H Hillman,
Katie L Allen Ziegler,
Zhifu Sun,
Jason A Wampfler,
Julie M Cunningham,
Jeff A Sloan,
Alex A Adjei,
Edith Perez, James R Jett
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ABSTRACT: We evaluated the role of glutathione-related genotypes on overall survival, time to progression, adverse events, and quality of life (QOL) in stage IIIB/IV non-small cell lung cancer patients who were stable or responding from initial treatment with platinum-based chemotherapy and subsequently randomized to receive daily oral carboxyaminoimidazole or a placebo.
Of the 186 total patients, 113 had initial treatment with platinum therapy and DNA samples of whom 46 also had QOL data. These samples were analyzed using six polymorphic DNA markers that encode five important enzymes in the glutathione metabolic pathway. Patient QOL was assessed using the Functional Assessment of Cancer Therapy-Lung and the UNISCALE QOL questionnaires. A clinically significant decline in QOL was defined as a 10% decrease from baseline to week-8. Multivariate analyses were used to evaluate the association of the genotypes on the four endpoints.
Patients carrying a GCLC 77 genotype had a worse overall survival (hazard ratio (HR) = 1.5, p = 0.05). Patients carrying the GPX1-CC genotype had a clinically significant decline in the UNISCALE (odds ratio (OR): 7.5; p = 0.04), total Functional Assessment of Cancer Therapy-Lung score (OR: 11.0; p = 0.04), physical (OR: 7.1; p = 0.03), functional (OR: 5.2; p = 0.04), and emotional well-being constructs (OR: 23.8; p = 0.01).
Genotypes of glutathione-related enzymes, especially GCLC, may be used as host factors in predicting patients' survival after platinum-based chemotherapy. GPX1 may be an inherited factor in predicting patients' QOL. Further investigation to define and measure the effects of these genes in chemotherapeutic regimens, drug toxicities, disease progression, and QOL are critical.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2009; 4(4):479-85. · 4.55 Impact Factor
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ABSTRACT: An analysis of 14 small cell lung cancer (SCLC) trials was performed to improve the current understanding of potential prognostic factors for overall survival (OS) and progression-free survival (PFS) in groups of patients with limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC) separately.
Data on 688 patients with LD-SCLC and 910 patients with ED-SCLC were included. Clinical and laboratory factors were tested for their prognostic significance using Cox regression models that were stratified by protocol. Recursive partitioning and amalgamation (RPA) analyses were used to identify prognostic subgroups.
Poorer performance status (PS) led to worse OS and PFS in the ED-SCLC group but not in the LD-SCLC group. The prognostic impact of PS was strong for men but weak for women in the ED-SCLC group (interaction P value <.012 for OS and PFS). Other negative prognostic factors included increased age and men for the LD-SCLC group and increased age, men, increased number of metastatic sites at baseline, and increased creatinine levels for the ED-SCLC group. In patients with the ED-SCLC, RPA analyses identified 5 subgroups with different prognosis based on baseline PS, creatinine levels, sex, and the number of metastatic sites.
The current pooled analysis identified baseline creatinine levels and the number of metastatic sites as important prognostic factors in patients with ED-SCLC in addition to the well established factors of sex, age, and PS. There was a significant interaction between sex and PS within the ED-SCLC group, suggesting that PS is highly prognostic in men but has no significant impact in women. Within the LD-SCLC group, only age and sex were identified as important prognostic factors. RPA analyses confirmed many of these findings.
Cancer 04/2009; 115(12):2721-31. · 4.77 Impact Factor
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2009; 4(3):271-2. · 4.55 Impact Factor
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ABSTRACT: To determine the value of positron emission tomography (PET) in diagnosing occult malignancies in patients with paraneoplastic neurologic syndromes (PNSs) at Mayo Clinic's site in Rochester, MN.
We retrospectively reviewed the medical charts of all 107 patients who underwent PET from January 1, 2000, to July 31, 2006, for the indication of suspected PNS. Three patients did not meet inclusion criteria. PET results were considered positive if increased fludeoxyglucose F 18 uptake indicated malignancy (24 patients). Results from computed tomography were interpreted as positive if any suspect lesion was consistent with malignancy (26 patients).
One hundred four patients with PNS were identified from the PET central database; 73 patients had at least 1 positive result for paraneoplastic antibody, and 31 had antibody-negative PNS. Malignancy was confirmed pathologically in 10 patients, of whom 8 had positive PET results. There were 2 cases of confirmed malignancy (fallopian tube adenocarcinoma and spindle cell uterine carcinoma) for which PET results were negative. Two patients with positive PET results declined biopsy. Computed tomography was able to identify 3 of the 10 malignancies detected. Five cases of malignancy were detected only by PET. All patients with confirmed malignancy had positive results for at least 1 paraneoplastic antibody. One patient with positive results for PNS antibody and negative PET results was diagnosed as having small cell carcinoma on a follow-up PET scan after 27 months. PET had sensitivity, specificity, positive predictive value, and negative predictive value of 80%, 67%, 53%, and 88%, respectively.
PET scan was shown to be more sensitive than computed tomography for detecting occult malignancy (confirmed by positive test results for autoantibody) among patients with suspected PNS. The greatest clinical utility of PET could be in its high negative predictive value.
Mayo Clinic Proceedings 09/2008; 83(8):917-22. · 5.70 Impact Factor
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ABSTRACT: Patients with schizophrenia sometimes receive substandard medical care. This study explored such disparities among lung cancer patients with underlying schizophrenia.
This retrospective study focused on patients with pre-existing schizophrenia (or in some instances schizoaffective disorder) and a lung cancer diagnosis made between 1980 and 2004. 'Disparity' was defined as a patient's having been prescribed less aggressive therapy for a potentially curable cancer based on state-of-the-art treatment standards for the time and for the cancer stage. Qualitative methods were used to assess healthcare providers' decision-making.
29 patients were included. The median age was 59 years; 38% were men. Twenty-three had non-small cell lung cancer and 6 small cell lung cancer; 17 had potentially curable cancers. Five of 17 had a 'disparity' in cancer care: (1) no cancer therapy was prescribed because of chronic obstructive pulmonary disease; (2) no cancer therapy was prescribed because of infection; (3) no chemotherapy was prescribed because the patient declined it; radiation was provided; (4) no chemotherapy was prescribed because of the patient's schizophrenia symptoms; radiation was administered; and (5) no surgery was performed because of disorientation from a lobotomy; radiation was prescribed. Comments from healthcare providers suggest reflection and ethical adjudication in decision-making.
Schizophrenia was never the sole reason for no cancer treatment in patients with potentially curable lung cancer. This study provides the impetus for others to begin to assess the effect of schizophrenia on lung cancer management in other healthcare settings.
Psycho-Oncology 08/2008; 17(7):721-5. · 3.34 Impact Factor
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ABSTRACT: Prognosis of lung cancer is markedly improved when cancers are resected in early stages (particularly in stage I). Previous investigations failed to show benefit with use of chest radiographs or sputum cytologies to screen for lung cancer among high-risk populations. More recently, computed tomography (CT) has been used as a screening technique and appears to detect lung cancer at earlier stages (e.g., stage I) compared with usual clinical practice. However, whether screening CT reduces death from lung cancer has not been clarified. This review examines the problem presented by lung cancer, the issues presented by screening, and the results of past and recent studies of lung cancer screening.
Seminars in Respiratory and Critical Care Medicine 07/2008; 29(3):233-40. · 2.43 Impact Factor
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Elizabeth A Johnson,
Randolph S Marks,
Sumithra J Mandrekar,
Shauna L Hillman,
Mark D Hauge,
Mitchel D Bauman,
Edward J Wos,
Dennis F Moore,
John W Kugler,
Harold E Windschitl,
David L Graham,
Albert M Bernath,
Tom R Fitch,
Gamini S Soori, James R Jett,
Alex A Adjei,
Edith A Perez
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ABSTRACT: This study assessed whether maintenance therapy with carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen.
After completion of chemotherapy, patients were randomized to receive daily oral CAI at 250mg or placebo. Treatment continued until patient refusal, disease progression or unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L).
Registration was halted early for slow accrual (targeted 360, randomized 186: 94 CAI, 92 placebo). All patients were off active treatment at time of analyses. Non-haematologic AEs (primarily grade 1, 2) observed significantly more often in the CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%), nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0% versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment for AEs, death on study or refusal more often in the CAI group (36.0% versus 8.7%, p<0.0001). No significant differences in survival or time to progression were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log rank p=0.54; 2.8 months versus 2.4 months, log rank p=0.50). More patients receiving CAI reported a clinically significant (10-point) decline in QOL particularly on the functional (58% versus 37%, p=0.05) construct of FACT-L and UNISCALE (72% versus 51%, p=0.04).
The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC.
Lung Cancer 06/2008; 60(2):200-7. · 3.43 Impact Factor
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The Oncologist 05/2008; 13(4):439-44. · 3.91 Impact Factor
