An Article published Online First and in an upcoming edition of The Lancet concludes that radiotherapy plus chemotherapy, with or without surgery, are both treatment options for patients with stage IIIA (N2) non-small-cell lung cancer. The Article is written by Dr Kathy Albain, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, IL, USA, and colleagues.

Non-small-cell lung cancer makes up some 80% of lung cancers, and its most common cause is long-term exposure to tobacco smoke. Of all cases of non-small-cell lung cancer, the disease is locally advanced in the chest only in about 30% (stage IIIA), where front-line surgery cannot cure the disease because it has already spread to lymph nodes in the centre of the chest (N2). In this phase III randomised controlled trial, the authors compared concurrent chemotherapy and radiotherapy followed by surgery with standard concurrent chemotherapy and radiotherapy without surgery, the current standard for this group patients.

Patients with stage IIIA (N2) non-small-cell lung cancer were randomly assigned to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m² on days 1, 8, 29, and 36] and etoposide [50 mg/m² on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent surgery and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS).

202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23•6 months in group 1 versus 22•2 months in group 2 (a non-statistically significant difference). Number of patients alive at 5 years was 37 in group 1 and 24 in group 2. Progression free survival (PFS) seemed better in group 1 than in group 2, median 12•8 months versus 10•5 months; the number of patients without disease progression at 5 years was 32 (group 1) versus 13 (group 2). Lower white blood cell counts (neutropenia) and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus 4 (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy*, but not pneumonectomy**, versus chemotherapy plus radiotherapy.

The authors suggest the reason for an absence of effect of surgery could be inadequate power in the trial or reduced delivery of later chemotherapy (cycles 3 and 4) in the surgery group. However they say the mostly likely reason could be increased mortality following pneumonectomy, mainly due to acute respiratory distress syndrome and other respiratory causes. The authors conclude: “Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA (N2) non-small-cell lung cancer… medically healthy patients with stage IIIA (N2) non-small-cell lung cancer should be assessed by a team skilled in multimodality treatment, and treatment options can be considered during assessment. On the basis of the findings of our study, patients should be counselled about the risks and potential benefits of definitive chemotherapy plus radiotherapy with and without a surgical resection (preferably by lobectomy).”

In an accompanying Comment, Dr Wilfried E E Eberhardt, West German Tumour Centre, University Hospital Essen of the University Duisburg-Essen, Essen, Germany, and colleagues say: “Can we undertake surgery in patients with stage IIIA (N2) NSCLC after induction chemoradiotherapy from now on? Yes, we can-selectively in patients with less extensive resection (eg, lobectomy) than pneumonectomy.”

Link to article

Source
The Lancet

HOUSTON, July 29 — Tanning beds have moved to the highest-risk cancer category of radiation sources in an update from the International Agency for Research on Cancer (IARC).

Citing evidence from case-control studies and a meta-analysis, the IARC monograph working group “raised the classification of the use of UV-emitting tanning devices to Group 1, ‘carcinogenic to humans,’ ” the authors reported in the August issue of The Lancet Oncology.

In a meta-analysis published in 2006, the IARC working group concluded that people who begin using tanning devices before age 30 have a 75% greater risk of cutaneous melanoma than the general population (Int J Cancer 2006; 120:1116-22).

The working group also cited case-control studies showing “consistent evidence of an association between the use of UV-emitting tanning devices and ocular melanoma.”

The IARC reclassified all forms of ultraviolet radiation as a single carcinogenic entity. Historically, mutations caused by exposure solar radiation had been attributed to UVB. However, the same mutation was identified in UVA-induced skin tumors in mice.

UVA, UVB, and UVC previously had been classified individually as “probably carcinogenic to humans” (group 2A in the IARC system). In the updated report, the IARC moved UV radiation as a whole into the highest-risk category, eliminating distinctions between UVA, UVB, and UVC.

With regard to other sources, the IARC working group found insufficient evidence to conclude that welders face an increased risk of UV radiation-induced ocular melanoma. However, the group said, “a full review of the carcinogenic hazards of welding will be undertaken with high priority.”

The working group also classified all forms of ionizing radiation as group 1. Forms of radiation affected by the action included radon, plutonium, radium, phosphorus-32, and radioiodines.

Working group member Nicholas Priest is an employee of Atomic Energy of Canada. Co-author Ron Mitchel is a consultant to Atomic Energy of Canada. Co-author Colin Muirhead disclosed a financial relationship with the UK Ministry of Defense. Co-author J. Hall disclosed a financial relationship with Electricite de France. Co-author A. Green disclosed a relationship with L’Oreal Recherche.

A new study by researchers at the Georgetown’s Lombardi Comprehensive Cancer Center finds a higher level of common household pesticides in the urine of children with acute lymphoblastic leukemia (ALL), a cancer that develops most commonly between three and seven years of age. The findings are published in the August issue of the journal Therapeutic Drug Monitoring.

Researchers caution that these findings should not be seen as cause-and-effect, only that the study suggests an association between pesticide exposure and development of childhood ALL.

“In our study, we compared urine samples from children with ALL and their mothers with healthy children and their moms. We found elevated levels of common household pesticides more often in the mother-child pairs affected by cancer,” says the study’s lead investigator, Offie Soldin, PhD, an epidemiologist at Lombardi. Soldin cautions, “We shouldn’t assume that pesticides caused these cancers, but our findings certainly support the need for more robust research in this area.”

The study was conducted between January 2005 and January 2008 with volunteer participants from Lombardi and Children’s National Medical Center who live in the Washington metropolitan area. It included 41 pairs of children with ALL and their mothers (cases), and 41 pairs of healthy children and their mothers (controls). For comparison purposes, the case pairs were matched with control pairs by age, sex and county of residence. Previous studies in agricultural areas of the country have suggested a relationship between pesticides and childhood cancers, but researchers say this is the first study conducted in a large, metropolitan area.

Urine samples were collected from all child-mother pairs and analyzed by the Centers for Disease Control and Prevention to look for evidence of organophosphates (OP), the chemical name of some household pesticides. The body breaks down OP into metabolites which can be tracked in urine samples. The researchers say pesticides were detected in the urine of more than half of the participants, but levels of two common OP metobolites, diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), were higher in the children with ALL compared to the control children (p< 0.03 and p< 0.05).

Also for the study, the mothers completed a questionnaire to collect information about the family’s exposure to pesticides, their medical history, home and neighborhood characteristics, diet, and history of smoke exposure. More case mothers (33 percent) than controls (14 percent) reported using insecticides in the home (p< 0.02), however there was no correlation found between high levels of the OP metabolites in urine and reported use of pesticides.

“We know pesticides - sprays, strips, or ‘bombs,’ are found in at least 85 percent of households, but obviously not all the children in these homes develop cancer. What this study suggests is an association between pesticide exposure and the development of childhood ALL, but this isn’t a cause-and-effect finding,” Soldin explains. “Future research would help us understand the exact role of pesticides in the development of cancer. We hypothesize that pre-natal exposure coupled with genetic susceptibility or an additional environmental insult after birth could be to blame.”

The authors report no related financial interests. The study was funded by Lombardi’s Cancer Center Support Grant from the National Cancer Institute, and by philanthropic support from Debbie and Scott Amey.

Source:
Karen Mallet

Georgetown University Medical Center