Monday, May 9, 2011

Taking the bite out of second cancer risk attributable to radiotherapy of primary first cancer

 Extract of my guest post at maiBlog, a radiology-focused blog.

"The increasing ranks of cancer survivors have brought new concerns into focus—second primary cancers now account for 18% of all cancer diagnosis and are the third most common cancer diagnosis in US. ... Radiotherapy, while a highly effective cancer treatment option, has long been considered to increase the risk of subsequent cancers, but convincing data had been lacking.  Now, an epidemiological study published by the National Cancer Institute in the April 2011 issue of Lancet Oncology journal shows that 92% of all second cancers are due to causes other than the radiation treatment of previous cancer. ..."

Click here to read full post at maiBlog.

___________________________

Complete Post Below:

Over the last forty years, we have made great strides in the diagnosis and treatment of cancer. According to the Centre for Disease Control and Prevention (CDC), the number of cancer survivors have steadily increased from three million in 1971 to over eleven million today; one in twenty Americans is a cancer survivor. The increasing ranks of cancer survivors have brought new concerns into focus‚Äîsecond primary cancers now account for 18% of all cancer diagnosis and are the third most common cancer diagnosis in US. Similar data is also emerging from other countries. Second primary cancers (a.k.a. second cancers) are new cancers that arise after the first incidence of any cancer. Second cancer may be in the same, surrounding or distant organs, and differ from metastatic cancer which is a result of primary first cancer cells disseminating to a distant organs (see a definition here).
Genetics and lifestyle behaviors, for instance, smoking, alcohol or poor diet, are partly responsible for second cancer, the treatment modalities during first cancer may also have a role. Both chemotherapy and radiotherapy can increase predisposition of other cells to cancer. Radiotherapy, while a highly effective cancer treatment option, has long been considered to increase the risk of subsequent cancers, but convincing data had been lacking. Now, an epidemiological study published by the National Cancer Institute in the April 2011 issue of Lancet Oncology journal shows that 92% of all second cancers are due to causes other than the radiation treatment of previous cancer.
This study relied on a National Cancer Institute resource called US Surveillance, Epidemiology and End Results (SEER) cancer registries. Since 1973, SEER registries have been collecting and reporting data on patient demographics, cancer diagnosis, tumor morphology tumor stage at diagnosis, first-line treatment and follow-up status. There are fifteen SEER registries which cover 28% of the US population from Conn. to Calif. with a racial make-up reflecting the overall US population. The authors analyzed data (collected from nine registries) for 647,672 patients who were 20 years or older (adult) and had been followed for a mean of 12 years since the primary cancer diagnosis. Their analyses included all (i.e., fifteen) solid-cancer sites, and cancers which had appeared after 5 years of first cancer were counted as second cancers. In this analysis, patients who had survived five or more years, nine percent developed second tumors‚Äînot all had received radiotherapy.
Radiotherapy, as part of initial first cancer management included external beam, brachytherapy or a combination of both. There was a variation in the use of radiotherapy across various cancer types. In this cohort, 60-80% of testicular (seminomas), brain, anal and laryngeal cancers were treated with radiotherapy, whereas less than 30% of non-small-cell lung and eye & orbit cancers were managed with radiotherapy. Yet, for every cancer type analyzed, the risk of second cancer was significant (Relative Risk, RR>1); the highest risk was for testicular (34%) and cervical(17%) cancers. However, of all the second cancers, only 8% could be attributed to radiotherapy during first cancer management. This is a much smaller percent than expected, and is a very good news for the radiology community. It helps communicate long-term risk of radiotherapy with respect to the potential benefit of tumor control and patient survival. Furthermore, the overall risk also decreases with time and by 15 years after the first diagnosis, only five excess cancers were found per 1000 cancer survivors.
The strengths of this study were: systemic analysis of all first cancer sites in adults, large population and over three decades of follow-up population data. However, there are some limitations: pediatric populations were excluded, also excluded from the study were patients who survived <5 years, those with hematological cancers, non-seminoma testicular cancers and small-cell lung cancer. The radiotherapy tools and equipment are continuously evolving and new technologies are being adopted. Thus, another look at these statistics will be warranted in coming years. But, for now, radiotherapy must be considered safe and should help professionals address anxiety of patients choosing a radiotherapy option.
This study was led by Amy Berrington de Gonzalez of Radiation Epidemiology Branch of National Cancer Institute, Bethesda, and included researchers from MD Anderson Cancer Institute, Houston, Texas.

Read more about the author, cancer biologist and biotech writer,Ajay K. Malik, PhD

References
Cancer Survivors‚ÄîUnited States, 2007. Morbidity and Mortality Weekly Report (MMWR). March 11, 2011;60(9):269-272 | FreeFullText |
de Gonzalez AB, Curtis RE, Kry SF, et al. Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries.Lancet Oncol. 2011 Apr;12(4):353-60. | PubMed | Scholar |

Tuesday, May 3, 2011

Webinar Report: Impact of Next Generation/Whole-Genome Sequencing on Companion Diagnostics

Biomarkers are increasingly part of pharmaceutical and clinical strategy.  By some estimates, the success rate of FDA approval of new cancer drugs is 75% if mechanism-of-action and predictive or prognostic biomarkers are clearly defined, whereas it is 25% without the biomarker information.  However, identifying new biomarkers for companion diagnosis (CDx) remains a challenge—the identification of KRAS-type biomarkers is rare, there is a double regulatory hurdle and revenue issues hamper pharmaceutical investment in this area.  Whole-genome sequencing is an important tool in the discovery of biomarkers.