Do dose-volume metrics predict pulmonary function changes in lung irradiation?

PURPOSE: To examine the ability of standard dose-volume metrics to predict pulmonary function changes as measured by pulmonary function tests (PFTs) in a group of patients with non-small-cell lung cancer treated with nonconventional beam arrangements on a Phase I dose-escalation study. In addition, we wanted to examine the correlation between these metrics. MATERIALS AND METHODS: Forty-three patients received a median treatment dose of 76.9 Gy (range 63-102.9). Eight patients also received induction chemotherapy with cisplatin and vinorelbine. They all had pre- and posttreatment PFTs >/=3 months (median 6.2) after treatment. The volume of normal lung treated to >20 Gy, effective volume, and mean lung dose were calculated for both lungs for all patients. Linear regression analysis was performed to determine whether correlations existed between the metrics and changes in the PFTs. Additionally, the three metrics were compared with each other to assess the degree of intermetric correlation. RESULTS: No correlation was found between the volume of normal lung treated to >20 Gy, effective volume, and mean lung dose and changes in the PFTs. Subgroup analyses of patients without atelectasis before irradiation, Stage I and II disease, or treatment without induction chemotherapy were also performed. Again, no correlation was found between the dose-volume metrics and the PFT changes. The intermetric correlation was good among all three dose-volume metrics. CONCLUSIONS: In this relatively small series of patients, dose-volume metrics that correlate with the risk of pneumonitis did not provide a good model to predict early changes in pulmonary function as measured with PFTs.     

Does HIV adversely influence the outcome in advanced non-small-cell lung cancer in the era of HAART?

The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced NSCLC. This suggests that the survival of patients with HIV-related NSCLC may have improved since the introduction of HAART, and this may be due to a decrease in HIV-related deaths.     

MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment?

Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.     

Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung?

Radiation therapy is widely considered the primary treatment for inoperable "non-small" cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung.     

Do multidisciplinary team meetings make a difference in the management of lung cancer?

BACKGROUND:

There is limited evidence regarding the effectiveness of multidisciplinary team (MDT) meetings in lung cancer. The objective of this study was to compare the patterns of care for patients with newly diagnosed lung cancer who were presented at a lung cancer MDT meeting with the patterns of care for patients who were not presented.

METHODS:

All patients who had lung cancer newly diagnosed in South West Sydney (SWS) between December 1, 2005, and December 31, 2008, were identified from the local Clinical Cancer Registry. Patient and tumor characteristics and treatment receipt were compared between patients who were and were not presented at MDT meetings. A logistic regression model was constructed to determine predictors for receiving treatment and survival.

RESULTS:

In total, there were 988 patients, including 504 patients who were presented at MDT meetings and 484 who were not presented at MDT meetings. The median patient age was 69 years and 73 years in the MDT group and the non‐MDT group, respectively (P < .01). There was no pathologic diagnosis for 13% of non‐MDT patients compared with 4% of MDT patients (P < .01). Treatment receipt for MDT patients versus non‐MDT patients was 12% versus 13%, respectively, for surgery (P value nonsignificant); 66% versus 33%, respectively, for radiotherapy (P < .001); 46% versus 29%, respectively, for chemotherapy (P < .001); and 66% versus 53%, respectively, for palliative care (P < .001). In patients with good performance status, the MDT group had significantly better receipt of radiotherapy among patients with stage I through IV nonsmall cell lung cancer (NSCLC) and had significantly better receipt of chemotherapy among patients with stage IV NSCLC. MDT discussion was an independent predictor of receiving radiotherapy, chemotherapy, and referral to palliative care but did not influence survival.

CONCLUSIONS:

MDT discussion was associated with better treatment receipt, which potentially may improve quality of life for patients with lung cancer. However, it did not improve survival. Cancer 2011;. © 2011 American Cancer Society.     

Targeting NF-κB in mouse models of lung adenocarcinoma

Xue et al. demonstrate response and increased survival but development of acquired resistance to proteasome and inhibitor-κB kinase inhibitors targeting NF-κB activation in adenocarcinomas of Kras-activated, p53-deficient mice.     

Sex hormones and oesophageal adenocarcinoma: influence of childbearing?

The male predominance of oesophageal adenocarcinoma might be explained by oestrogen protection in women. If true, female patients might have sex hormonal disturbances rendering impaired fertility. The influence of childbearing on the risk of oesophageal adenocarcinoma was investigated in a Swedish population-based case (n=63) -control (n=141) study. Childless women were not at increased risk compared to childbearing (OR=0.82; 95% CI=0.25-2.72), as neither were women with 0-1 children compared to women with at least three children (OR=0.93; 95% CI=0.35-2.49). In conclusion, we found no inverse association between childbearing and oesophageal adenocarcinoma.     

β-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma

Aimβ-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that β-carotene stimulates cAMP signalling in vitro. Here, we have tested the hypothesis that β-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signalling.MethodsPAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), followed by β-carotene for 1.5 years. Incidence, multiplicity and size of lung tumours were recorded, and phosphorylated CREB and ERK1/2 in tumour cells were determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC.Resultsβ-Carotene increased lung tumour multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours.ConclusionsOur data suggest that β-carotene promotes the development of PAC via increased cAMP signalling.     

The beginning of the end of the lung cancer epidemic in Dutch women?

In some European countries, female lung cancer mortality and incidence have started to decrease or flatten out, whereas they are still rising in The Netherlands. We present recent mortality and incidence trends of lung cancer and smoking trends in The Netherlands to show the end of the lung cancer epidemic in Dutch women. Lung cancer mortality and incidence rates by gender were analyzed for 4 age groups (20-44, 45-49, 50-54 and 55-59), and smoking prevalence rates were examined for women using joinpoint regression and birth cohort analysis. Data on mortality were collected for the period 1960-2006, incidence for the period 1989-2003 and smoking prevalence for the period 1988-2007. Because of decreasing lung cancer mortality and incidence rates among males and dramatically increasing rates among females, rates of young males were surpassed by those of females after the mid-1990s. However, although in young women (20-49) mortality increased with 4-5% per year, it flattened out (no significant in- or decreases) since 1999. Among older women, mortality rates were still increasing markedly. Mortality rates and smoking prevalence tended to decrease in women born after the 1950s. This is the first report suggesting that the lung cancer epidemic in Dutch women is coming to an end. Although the increase in lung cancer incidence and mortality among Dutch women has been one of the most dramatic in Europe, the recent decrease in young women is expected to be followed by a future leveling off or a slight decrease in overall female lung cancer rates.     

What is the origin of pancreatic adenocarcinoma?

The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.     

Cancers of the lung,head and neck on the rise：perspectives on the genotoxicity of air pollution

Outdoor air pollution has been recently classified as a class I human carcinogen by the World Health Organization （WHO）. Cumulative evidence from across the globe shows that polluted air is associated with increased risk of lung, head and neck, and nasopharyngeal cancers--all of which affect the upper aerodigestive tract. Importantly, these cancers have been previously linked to smoking. In this article, we review epidemiologic and experimental evidence of the genotoxic and mutagenic effects of air pollution on DNA, purportedly a key mechanism for cancer development. The alarming increase in cancers of the upper aerodigestive tract in Asia suggests a need to focus government efforts and research on reducing air pollution, promoting clean energy, and investigating the carcinogenic effects of air pollution on humans.