Quality of life and survival in the 2 years after surgery for non small-cell lung cancer.

J Clin Oncol. 2008 Jan 10;26(2):233-41. Epub 2007 Dec 17

Kenny PM, King MT, Viney RC, Boyer MJ, Pollicino CA, McLean JM, Fulham MJ, McCaughan BC.

Centre for Health Economics Research and Evaluation, University of Technology, Sydney, PO Box 123, Broadway, Sydney, New South Wales 2007, Australia.: patsy.kenny@chere.uts.edu.au

PURPOSE: Although surgery for early-stage non-small-cell lung cancer (NSCLC) is known to have a substantial impact on health-related quality of life (HRQOL), there are few published studies about HRQOL in the longer term. This article examines HRQOL and survival in the 2 years after surgery. PATIENTS AND METHODS: Patients with clinical stage I or II NSCLC (n = 173) completed HRQOL questionnaires before surgery, at discharge, 1 month after surgery, and then every 4 months for 2 years. HRQOL was measured with a generic cancer questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ] C30) and a lung cancer-specific questionnaire (EORTC QLQ-LC13). Data were analyzed to examine the impact of surgery and any subsequent therapy, and to describe the trajectories of those who remained disease free at 2 years and those with recurrent cancer diagnosed during follow-up. RESULTS: Disease recurred within 2 years for 36% of patients and 2-year survival was 65%. Surgery substantially reduced HRQOL across all dimensions except emotional functioning. HRQOL improved in the 2 years after surgery for patients without disease recurrence, although approximately half continued to experience symptoms and functional limitations. For those with recurrence within 2 years, there was some early postoperative recovery in HRQOL, with subsequent deterioration across most dimensions. CONCLUSION: Surgery had a substantial impact on HRQOL, and although many disease-free survivors experienced recovery, some lived with long-term HRQOL impairment. HRQOL generally worsened with disease recurrence. The study results are important for informed decision making and ongoing supportive care for patients with operable NSCLC.

Sourec: Pubmed – PMID: 18086802 [PubMed - in process]

Two Studies Identify Drivers of Metastases

A study published in the January 10 Nature has pinpointed several microRNAs (miRNAs) – tiny RNA strands that regulate gene expression – that help suppress breast cancer metastases.

Researchers from Memorial Sloan-Kettering Cancer Center examined miRNAs in breast cancer cell lines that were highly metastatic to bone and lung compared with control breast cancer cell lines. They chose to focus further studies on the six miRNAs whose expression was most decreased in the metastatic cells.

Restoring the function of three of these miRNAs – called miR-335, miR-206, and miR-126 – by gene therapy significantly reduced the formation of bone metastases in mice implanted with the breast cancer cell lines. Rare cells that did metastasize had decreased expression of the three miRNAs.

To measure the expression of these miRNAs in human tumors, the investigators used archived tissue samples from 11 women with metastatic breast cancer and 9 women whose cancer did not metastasize. They found that patients whose primary tumors had low expression of the three miRNAs “had a shorter median time to metastatic relapse.”

In particular, low levels of miR-335 or miR-126 “were associated with very poor overall metastasis-free survival compared to the group whose tumors expressed a high level of these miRNAs.” Further studies identified genes regulated by miR-335 that are directly associated with relapse.

A second study published in the January 11 Science identified a specific contribution of cells in the tumor microenvironment involved in the angiogenic switch – the generation of a tumor blood supply – and the associated progression of lung micrometastases to deadly macrometastases.

Researchers from Cold Spring Harbor Laboratory found that micrometastases that recruit a type of cell called a bone marrow-derived endothelial progenitor cell (EPC) to their immature blood vessels undergo development of a blood supply, in both xenograft and spontaneous mouse models of cancer.

The researchers also identified a protein called Id1 that is needed to draw the EPCs to the tumor site. When this protein was suppressed in a mouse model, the number of EPCs in the bloodstream was significantly reduced, and tumor blood vessel growth was suppressed. “These findings …suggest that the efficacy of antiangiogenic inhibitors used in clinical trials…may be a consequence of directly targeting [bone marrow]-derived EPCs, as well as the nascent tumor vasculature,” conclude the authors.

Source: NCI Cancer Bulletin. January 22, 2008

Inhibiting Tumor Angiogenesis in Children – Clinical Trial

Name of the Trial
Phase I Study of Cediranib in Pediatric Patients with Refractory or Recurrent Extracranial Malignant Solid Tumors or Acute Myeloid Leukemia (NCI-06-C-0152). See the protocol summary at http://cancer.gov/clinicaltrials/NCI-06-C-0152.

Principal Investigator
Dr. Elizabeth Fox, NCI Center for Cancer Research

Why This Trial Is Important
Great progress has been made in the treatment of childhood cancers over the past 30 years, thanks primarily to advances in chemotherapy and a high level of participation in clinical trials by pediatric patients. This progress, however, is in danger of stalling without new treatment advances.

One approach that has shown effectiveness in the treatment of some adult cancers is inhibiting the growth of new blood vessels to tumors (i.e., blocking tumor angiogenesis). Without angiogenesis, solid tumors are unable to grow beyond a few millimeters in size. Because drugs that inhibit angiogenesis may cause different side effects in children than they do in adults, it is important to carefully test their use in pediatric cancer patients.

In this trial, researchers are testing an angiogenesis inhibitor called cediranib in pediatric patients who have solid tumors (except brain tumors) or acute myeloid leukemia (AML), a type of blood cancer. Although solid tumors are not formed in AML, there is evidence that a protein known to be important in tumor angiogenesis (i.e., vascular endothelial growth factor, or VEGF) may also be important for the growth of AML cells. Cediranib blocks all three known receptor proteins for VEGF.

“Solid tumors in children tend to be highly vascular, and adult AML patients with elevated levels of VEGF typically don’t survive as long as those with lower levels,” said Dr. Fox. “So, there’s a strong rationale for using VEGF inhibitors for these cancers. However, it is vitally important to assess the toxicities and establish the appropriate dosage of cediranib for pediatric patients.

“Furthermore, we plan to study how cediranib affects a number of markers related to cancer progression and, at least preliminarily, determine tumor responses to cediranib in these patients,” she added.

For More Information
For more information about this trial, see http://cancer.gov/clinicaltrials/NCI-06-C-0152

Source: NCI Cancer Bulletin. January 22, 2008 

Trial Shows Some Benefit of Adjuvant Chemo for Early Colorectal Cancer

A large European trial designed to determine the value of adjuvant chemotherapy after surgery for stage II colorectal cancer has found that patients receive “small but definite benefit” in both survival and risk of recurrence, say researchers at the University of Birmingham in England.

The QUick And Simple And Reliable (QUASAR) Trial Collaborative Group, led by Dr. Richard Gray, reported results on 3,239 patients after 5.5 years median follow-up in the December 15, 2007, Lancet. Compared with observation alone, patients receiving chemotherapy had an 18-percent reduction in risk of death, which, in a population whose mortality rate is about 20 percent, conferred an absolute reduction of 3.6 percent at 5 years. The 22-percent reduction in risk of recurrence occurred almost completely in the first 2 years, and then leveled off.

“Chemotherapy seems to prevent a proportion of recurrences and deaths rather than just delaying them,” wrote the authors, “which makes the life-years gained more substantial, especially for younger patients.”

Drs. David Cunningham and Naureen Starling of the Royal Marsden Hospital in Surrey wrote in an editorial that the QUASAR results do not fully resolve all of the issues in this population, and that “identification of patients most likely to benefit from therapy remains important.” Subgroup analyses are underway.

Better information about these groups, they wrote, may help patients and physicians assess the risk/benefit ratio among the three options currently in use: fluorouracil with oxaliplatin, fluoropyrimidine, or observation. These newer drugs and combinations have largely supplanted the drugs tested in QUASAR.

Source: NCI Cancer Bulletin. January 8, 2008

Allogeneic Transplant Does Not Increase Survival in High-Risk ALL

In a collaborative clinical trial from the UK Medical Research Council and the U.S. Eastern Cooperative Oncology Group, adult patients with standard-risk Philadelphia-chromosome-negative acute lymphoblastic leukemia (ALL) had significantly increased overall survival after high-dose, chemotherapy-induced first remission followed by allogeneic stem cell transplantation. However, while patients with high-risk ALL had a decrease in the risk of relapse with allogeneic transplantation, their overall survival did not significantly increase, due to the high rate of transplant-related mortality.

“Surprising though it might appear, the high-risk patients benefit less from having a donor than the standard-risk patients in terms of overall survival,” state the authors in their paper published online November 29 in Blood. “This is an important finding since there is often a view that high-risk patients should go immediately to allogeneic transplant.”

The trial also tested autologous (self) transplantation versus maintenance chemotherapy for patients who did not have a matched sibling donor available for allogeneic transplantation. Unmatched patients who went into remission after the initial high-dose chemotherapy were randomly assigned to receive either autologous transplantation or 2.5 years of maintenance chemotherapy.

Those patients receiving chemotherapy had significantly improved overall survival compared with patients undergoing autologous transplantation, and there was no significant difference in nonrelapse (i.e., treatment-related) mortality between the two groups. However, in an analysis comparing all patients with a donor versus those without a donor, those with a donor had better overall survival rates.

“Sibling donor allogeneic transplant is the treatment of choice for adults with standard-risk ALL in remission providing the greatest chance for a long-term survival. Autologous transplant has a less favorable outcome than consolidation/maintenance chemotherapy for those without a donor,” conclude the authors.

Source: NCI Cancer Bulletin.  December 18, 2007