The Journal of Community and Supportive Oncology

Among prostate cancers that are judged to be low risk after physical exam and biopsy, and which thus are candidates for active surveillance, 33%-45% are upgraded or upstaged when the patient decides instead to undergo radical prostatectomy, according to a report in the February issue of Journal of Urology.

Researchers analyzed data regarding tumor and patient features for 4,500 cases in a national Swedish database of prostate cancers diagnosed during a 4-year period. All of these cases were judged to be low risk on the basis of Gleason scores, PSA findings, and biopsy results, but all of the men elected to undergo radical prostatectomy, said Dr. Annelies Vellekoop of New York University and Manhattan Veterans Affairs Medical Center, New York, and her associates.

Even though these cases met stringent criteria for active surveillance according to several different protocols, 33%-45% of them (depending on the protocol) were found at surgery to have adverse pathology signaling that the cancers were of higher risk than anticipated (J. Urol. 2014;191:350-7).

Three predictors of upstaging/upgrading – age over 60 years, high PSA level, and stage T2 cancer on biopsy – are already known to raise risk and are included in most risk-assessment criteria. But two other factors – PSA density greater than 0.15 ng/mL and the linear extent of cancer in mm within biopsy specimens – were found to be highly predictive in this study and should be considered as additional criteria to include in risk assessments, the investigators said.

This study was supported by the Swedish Research Council, the Swedish Cancer Foundation, Vasterbotten County Council, and Lion’s Cancer Research Foundation at Umea University. Dr. Vellekoop reported no financial conflicts of interest; one of her associates reported ties to Sanofi.

tor@frontlinemedcom.com

Among prostate cancers that are judged to be low risk after physical exam and biopsy, and which thus are candidates for active surveillance, 33%-45% are upgraded or upstaged when the patient decides instead to undergo radical prostatectomy, according to a report in the February issue of Journal of Urology.

Researchers analyzed data regarding tumor and patient features for 4,500 cases in a national Swedish database of prostate cancers diagnosed during a 4-year period. All of these cases were judged to be low risk on the basis of Gleason scores, PSA findings, and biopsy results, but all of the men elected to undergo radical prostatectomy, said Dr. Annelies Vellekoop of New York University and Manhattan Veterans Affairs Medical Center, New York, and her associates.

Even though these cases met stringent criteria for active surveillance according to several different protocols, 33%-45% of them (depending on the protocol) were found at surgery to have adverse pathology signaling that the cancers were of higher risk than anticipated (J. Urol. 2014;191:350-7).

Three predictors of upstaging/upgrading – age over 60 years, high PSA level, and stage T2 cancer on biopsy – are already known to raise risk and are included in most risk-assessment criteria. But two other factors – PSA density greater than 0.15 ng/mL and the linear extent of cancer in mm within biopsy specimens – were found to be highly predictive in this study and should be considered as additional criteria to include in risk assessments, the investigators said.

This study was supported by the Swedish Research Council, the Swedish Cancer Foundation, Vasterbotten County Council, and Lion’s Cancer Research Foundation at Umea University. Dr. Vellekoop reported no financial conflicts of interest; one of her associates reported ties to Sanofi.

tor@frontlinemedcom.com

Among prostate cancers that are judged to be low risk after physical exam and biopsy, and which thus are candidates for active surveillance, 33%-45% are upgraded or upstaged when the patient decides instead to undergo radical prostatectomy, according to a report in the February issue of Journal of Urology.

Researchers analyzed data regarding tumor and patient features for 4,500 cases in a national Swedish database of prostate cancers diagnosed during a 4-year period. All of these cases were judged to be low risk on the basis of Gleason scores, PSA findings, and biopsy results, but all of the men elected to undergo radical prostatectomy, said Dr. Annelies Vellekoop of New York University and Manhattan Veterans Affairs Medical Center, New York, and her associates.

Even though these cases met stringent criteria for active surveillance according to several different protocols, 33%-45% of them (depending on the protocol) were found at surgery to have adverse pathology signaling that the cancers were of higher risk than anticipated (J. Urol. 2014;191:350-7).

Three predictors of upstaging/upgrading – age over 60 years, high PSA level, and stage T2 cancer on biopsy – are already known to raise risk and are included in most risk-assessment criteria. But two other factors – PSA density greater than 0.15 ng/mL and the linear extent of cancer in mm within biopsy specimens – were found to be highly predictive in this study and should be considered as additional criteria to include in risk assessments, the investigators said.

This study was supported by the Swedish Research Council, the Swedish Cancer Foundation, Vasterbotten County Council, and Lion’s Cancer Research Foundation at Umea University. Dr. Vellekoop reported no financial conflicts of interest; one of her associates reported ties to Sanofi.

tor@frontlinemedcom.com

In July 2013, afatinib was approved by the US Food and Drug Administration for first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Quiagen’s therascreen EGFR RGQ PCR Kit for detection of EGFR exon 19 deletions (del19) and exon 21 (L858R) substitution mutations was concurrently approved. Afatinib is an oral selective ErbB family inhibitor that irreversibly blocks signaling from EGFR/ErbB1, HER2/ErbB2, and ErbB4 and has shown broad-spectrum activity against tumor cells with EGFR mutations.

Click on the PDF icon at the top of this introduction to read the full article.

In July 2013, afatinib was approved by the US Food and Drug Administration for first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Quiagen’s therascreen EGFR RGQ PCR Kit for detection of EGFR exon 19 deletions (del19) and exon 21 (L858R) substitution mutations was concurrently approved. Afatinib is an oral selective ErbB family inhibitor that irreversibly blocks signaling from EGFR/ErbB1, HER2/ErbB2, and ErbB4 and has shown broad-spectrum activity against tumor cells with EGFR mutations.

Click on the PDF icon at the top of this introduction to read the full article.

In July 2013, afatinib was approved by the US Food and Drug Administration for first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Quiagen’s therascreen EGFR RGQ PCR Kit for detection of EGFR exon 19 deletions (del19) and exon 21 (L858R) substitution mutations was concurrently approved. Afatinib is an oral selective ErbB family inhibitor that irreversibly blocks signaling from EGFR/ErbB1, HER2/ErbB2, and ErbB4 and has shown broad-spectrum activity against tumor cells with EGFR mutations.

Click on the PDF icon at the top of this introduction to read the full article.

Background As non–small-cell lung cancer (NSCLC) treatments improve and patients live longer, it is important to develop interventions to help patients live fuller lives. We sought to identify key components of quality of life (QOL) in determining therapeutic decision making and overall value of life extension in patients with NSCLC.

Methods Three focus groups (n = 16) and telephone interviews (n = 15) were conducted with NSCLC patients (N = 31) to explore symptoms considered important to QOL. A trade-off format was used to assess the value of life extension relative to QOL. Patients were asked to consider a hypothetical treatment option offering a modest (3 month) life extension.

Results Patients’ mean age was 61.6 years, 67.6% were women, 77.4% were white, and 48.4% had stage III/IV disease. In all, 68% of patients conceptualized emotions as symptoms of NSCLC. Key symptoms changed over time: Patients reported feeling shock and fear at diagnosis (74%), and feeling fear or loneliness during the beginning of therapy (55%). Additionally, patients who reported successfully connecting with other NSCLC patients (peers), support groups, and/or community members reported a positive shift in feelings (52%) as they continued therapy or moved into a posttherapy phase. Financially, 23% of patients reported being adversely affected by copayments, 36% by unexpected gaps in coverage, and 39% by other bills. Patients reported that the most important dimension driving their decision making about life-extending therapy was somatic (84%), followed by functional (32%), relational (23%), and emotional (10%) dimensions.

Limitations Study participants were likely to have received some education or support from the recruiting cancer advocacy and patient education/support organizations. In addition, participants were of a higher socioeconomic status than the average lung cancer patient population.

Conclusions Patients with NSCLC conflated emotional well-being after diagnosis with symptoms of their cancer and treatment toxicities. Somatic QOL concerns emerged ahead of functional, emotional, and relational QOL concerns as the dominant driver of therapeutic decision making.
Funding This study was funded by Daiichi Sankyo Inc.

Click on the PDF icon at the top of this introduction to read the full article.

Background As non–small-cell lung cancer (NSCLC) treatments improve and patients live longer, it is important to develop interventions to help patients live fuller lives. We sought to identify key components of quality of life (QOL) in determining therapeutic decision making and overall value of life extension in patients with NSCLC.

Methods Three focus groups (n = 16) and telephone interviews (n = 15) were conducted with NSCLC patients (N = 31) to explore symptoms considered important to QOL. A trade-off format was used to assess the value of life extension relative to QOL. Patients were asked to consider a hypothetical treatment option offering a modest (3 month) life extension.

Results Patients’ mean age was 61.6 years, 67.6% were women, 77.4% were white, and 48.4% had stage III/IV disease. In all, 68% of patients conceptualized emotions as symptoms of NSCLC. Key symptoms changed over time: Patients reported feeling shock and fear at diagnosis (74%), and feeling fear or loneliness during the beginning of therapy (55%). Additionally, patients who reported successfully connecting with other NSCLC patients (peers), support groups, and/or community members reported a positive shift in feelings (52%) as they continued therapy or moved into a posttherapy phase. Financially, 23% of patients reported being adversely affected by copayments, 36% by unexpected gaps in coverage, and 39% by other bills. Patients reported that the most important dimension driving their decision making about life-extending therapy was somatic (84%), followed by functional (32%), relational (23%), and emotional (10%) dimensions.

Limitations Study participants were likely to have received some education or support from the recruiting cancer advocacy and patient education/support organizations. In addition, participants were of a higher socioeconomic status than the average lung cancer patient population.

Conclusions Patients with NSCLC conflated emotional well-being after diagnosis with symptoms of their cancer and treatment toxicities. Somatic QOL concerns emerged ahead of functional, emotional, and relational QOL concerns as the dominant driver of therapeutic decision making.
Funding This study was funded by Daiichi Sankyo Inc.

Click on the PDF icon at the top of this introduction to read the full article.

Background As non–small-cell lung cancer (NSCLC) treatments improve and patients live longer, it is important to develop interventions to help patients live fuller lives. We sought to identify key components of quality of life (QOL) in determining therapeutic decision making and overall value of life extension in patients with NSCLC.

Methods Three focus groups (n = 16) and telephone interviews (n = 15) were conducted with NSCLC patients (N = 31) to explore symptoms considered important to QOL. A trade-off format was used to assess the value of life extension relative to QOL. Patients were asked to consider a hypothetical treatment option offering a modest (3 month) life extension.

Results Patients’ mean age was 61.6 years, 67.6% were women, 77.4% were white, and 48.4% had stage III/IV disease. In all, 68% of patients conceptualized emotions as symptoms of NSCLC. Key symptoms changed over time: Patients reported feeling shock and fear at diagnosis (74%), and feeling fear or loneliness during the beginning of therapy (55%). Additionally, patients who reported successfully connecting with other NSCLC patients (peers), support groups, and/or community members reported a positive shift in feelings (52%) as they continued therapy or moved into a posttherapy phase. Financially, 23% of patients reported being adversely affected by copayments, 36% by unexpected gaps in coverage, and 39% by other bills. Patients reported that the most important dimension driving their decision making about life-extending therapy was somatic (84%), followed by functional (32%), relational (23%), and emotional (10%) dimensions.

Limitations Study participants were likely to have received some education or support from the recruiting cancer advocacy and patient education/support organizations. In addition, participants were of a higher socioeconomic status than the average lung cancer patient population.

Conclusions Patients with NSCLC conflated emotional well-being after diagnosis with symptoms of their cancer and treatment toxicities. Somatic QOL concerns emerged ahead of functional, emotional, and relational QOL concerns as the dominant driver of therapeutic decision making.
Funding This study was funded by Daiichi Sankyo Inc.

Click on the PDF icon at the top of this introduction to read the full article.

Background Vitamin D deficiency is common in the United States. Regardless of whether or not vitamin D deficiency increases the risk of cancer and decreases survival of cancer, the established adverse impact of its deficiency on bone health is of particular concern for cancer patients. The extent of vitamin D deficiency is not well defined in the oncology setting, and there are no standardized protocols for screening and supplementation for individuals found to be deficient in vitamin D.

Objective To determine the prevalence of vitamin D deficiency as measured by levels of serum 25-hydroxyvitamin D (25[OH]D) in cancer patients at an outpatient oncology practice.

Methods A total of 177 patients representing a range of oncologic diagnoses were tested for 25(OH)D between January 1, 2011 and December 31, 2011. Suboptimal vitamin D levels were defined either as less than 20 ng/mL or less than 30 ng/mL, according to standards proposed by the Institute of Medicine and the Endocrine Society, respectively.

Limitations The point of testing was subjective to the clinician. Some patients may have had their vitamin D levels tested and treated elsewhere, therefore that data was not captured.

Results At baseline, 18.1% of patients tested had vitamin D levels of less than 20 ng/ml, and 49.1% of patients had vitamin D levels of less than 30 ng/ml. Follow-up rates were low. In all, 54% of patients with 25(OH)D levels of less than 30 ng/ml obtained a second reading, and only 38% of those patients achieved sufficient levels at the second reading.

Conclusion Vitamin D deficiency is prevalent in patients with cancer and should be monitored in patients who are at high risk for vitamin D deficiency or poor bone health.

Click on the PDF icon at the top of this introduction to read the full article.

Background Vitamin D deficiency is common in the United States. Regardless of whether or not vitamin D deficiency increases the risk of cancer and decreases survival of cancer, the established adverse impact of its deficiency on bone health is of particular concern for cancer patients. The extent of vitamin D deficiency is not well defined in the oncology setting, and there are no standardized protocols for screening and supplementation for individuals found to be deficient in vitamin D.

Objective To determine the prevalence of vitamin D deficiency as measured by levels of serum 25-hydroxyvitamin D (25[OH]D) in cancer patients at an outpatient oncology practice.

Methods A total of 177 patients representing a range of oncologic diagnoses were tested for 25(OH)D between January 1, 2011 and December 31, 2011. Suboptimal vitamin D levels were defined either as less than 20 ng/mL or less than 30 ng/mL, according to standards proposed by the Institute of Medicine and the Endocrine Society, respectively.

Limitations The point of testing was subjective to the clinician. Some patients may have had their vitamin D levels tested and treated elsewhere, therefore that data was not captured.

Results At baseline, 18.1% of patients tested had vitamin D levels of less than 20 ng/ml, and 49.1% of patients had vitamin D levels of less than 30 ng/ml. Follow-up rates were low. In all, 54% of patients with 25(OH)D levels of less than 30 ng/ml obtained a second reading, and only 38% of those patients achieved sufficient levels at the second reading.

Conclusion Vitamin D deficiency is prevalent in patients with cancer and should be monitored in patients who are at high risk for vitamin D deficiency or poor bone health.

Click on the PDF icon at the top of this introduction to read the full article.

Background Vitamin D deficiency is common in the United States. Regardless of whether or not vitamin D deficiency increases the risk of cancer and decreases survival of cancer, the established adverse impact of its deficiency on bone health is of particular concern for cancer patients. The extent of vitamin D deficiency is not well defined in the oncology setting, and there are no standardized protocols for screening and supplementation for individuals found to be deficient in vitamin D.

Objective To determine the prevalence of vitamin D deficiency as measured by levels of serum 25-hydroxyvitamin D (25[OH]D) in cancer patients at an outpatient oncology practice.

Methods A total of 177 patients representing a range of oncologic diagnoses were tested for 25(OH)D between January 1, 2011 and December 31, 2011. Suboptimal vitamin D levels were defined either as less than 20 ng/mL or less than 30 ng/mL, according to standards proposed by the Institute of Medicine and the Endocrine Society, respectively.

Limitations The point of testing was subjective to the clinician. Some patients may have had their vitamin D levels tested and treated elsewhere, therefore that data was not captured.

Results At baseline, 18.1% of patients tested had vitamin D levels of less than 20 ng/ml, and 49.1% of patients had vitamin D levels of less than 30 ng/ml. Follow-up rates were low. In all, 54% of patients with 25(OH)D levels of less than 30 ng/ml obtained a second reading, and only 38% of those patients achieved sufficient levels at the second reading.

Conclusion Vitamin D deficiency is prevalent in patients with cancer and should be monitored in patients who are at high risk for vitamin D deficiency or poor bone health.

Click on the PDF icon at the top of this introduction to read the full article.

Researchers have identified two novel panels of microRNAs that eventually might be used to screen patients for pancreatic cancer, distinguishing affected patients from healthy individuals and from people who have other diseases of the pancreas, particularly pancreatitis, according to a report published online Jan. 21 in JAMA.

The two microRNA panels were better than standard serum cancer antigen 19-9 (CA19-9) testing at identifying pancreatic cancer within the initial study cohort used to assess hundreds of microRNA candidates. However, CA19-9 had better diagnostic accuracy in the validation cohort used to replicate those results. Combining the results of either microRNA panel with CA19-9 offered the best diagnostic accuracy of all, said Dr. Nicolai A. Schultz, of the department of oncology, Herlev Hospital and Copenhagen University Hospital, and his associates (JAMA 2013;311:392-404).

The discovery may lead to earlier diagnosis of pancreatic cancer at a stage when it is more treatable. At present, only 20% of patients can be operated on with curative intent, because most already have advanced disease by the time they are diagnosed, Dr. Schultz and his colleagues said.

However, the investigators emphasized that their findings are preliminary. "Further research is necessary to understand whether these microRNAs have clinical implications as a screening test for early detection of pancreatic cancer and how much this information adds to serum CA19-9," they noted.

The investigators began their search for relevant biomarkers by screening whole blood samples for the presence of any of 754 microRNAs suspected of being expressed in circulating blood by pancreatic cancers. MicroRNAs are small (17-25 nucleotides long), noncoding, single-stranded RNAs that promote oncogenesis by inhibiting the expression of tumor suppressor genes or by upregulating the expression of oncogenes. They are active in the pathogenesis, progression, and metastasis of pancreatic cancer.

The blood samples had been taken from 409 patients with histologically verified pancreatic cancer and 337 control patients, consisting of 25 patients with chronic pancreatitis and 312 healthy blood donors. Samples were drawn from the pancreatic cancer patients before they underwent any treatment; 44 had resectable tumors, and 365 had unresectable tumors.

The microRNA panels were identified and tested in a three-step process using discovery, training, and validation cohorts of patients.

In the discovery cohort, 38 microRNAs were found to have the potential to distinguish pancreatic cancer patients from other participants. Thirteen of those microRNAs were the strongest predictors and were used to develop the two diagnostic panels, which were then tested in the validation cohort.

The first diagnostic panel, termed index I, comprised 4 microRNAs, and the second panel, index II, comprised 10 microRNAs. Both panels correctly diagnosed pancreatic cancer in 85% of affected patients and correctly diagnosed chronic pancreatitis in 29% of affected patients.

Among control patients, index I correctly ruled out pancreatic disease in 48% and index II in 54%. When CA19-9 results were added to the panel results, index I correctly ruled out pancreatic disease in 98% of the control patients, and index II did so in 89%.

Thus, "the indices do achieve some separation of pancreatic cancer from healthy participants, but not a complete separation," Dr. Schultz and his associates said.

"When this microRNA biomarker study was designed in 2008, the aim was to identify microRNAs in whole blood that could identify pancreatic cancer (local, locally advanced, and metastatic) in individuals thought to be healthy," the investigators explained. "We first wanted to test the extremes (i.e., patients with known pancreatic cancer vs healthy blood donors), because if panels of microRNA could not differentiate patients with . . . high tumor burden from these healthy individuals, it would be difficult to develop a diagnostic microRNA test for patients with small tumors and low-stage cancer.

"In the future, we will assess the accuracy of indices I and II in combination with serum CA19-9 in large cohorts of patients either seen by a family physician or referred to hospitals on suspicion of cancer ... and assess whether it is possible to identify patients with pancreatic cancer at an early stage," Dr. Schultz and his associates said.

This study was supported by Herlev Hospital; the Danish Ministry of Science, Technology, and Innovation; the Danish Cancer Society; Region Hovedstadens forskinings fond til Sundhedsforskning; Aase og Ejnar Danielsens Fond; and Prosektor Axel Søeborg Ohlsen og Else Søeborg Ohlsen Mindelegat. Dr. Schultz and his associates reported holding a European patent application submitted by Copenhagen University Hospital.

Researchers have identified two novel panels of microRNAs that eventually might be used to screen patients for pancreatic cancer, distinguishing affected patients from healthy individuals and from people who have other diseases of the pancreas, particularly pancreatitis, according to a report published online Jan. 21 in JAMA.

The two microRNA panels were better than standard serum cancer antigen 19-9 (CA19-9) testing at identifying pancreatic cancer within the initial study cohort used to assess hundreds of microRNA candidates. However, CA19-9 had better diagnostic accuracy in the validation cohort used to replicate those results. Combining the results of either microRNA panel with CA19-9 offered the best diagnostic accuracy of all, said Dr. Nicolai A. Schultz, of the department of oncology, Herlev Hospital and Copenhagen University Hospital, and his associates (JAMA 2013;311:392-404).

The discovery may lead to earlier diagnosis of pancreatic cancer at a stage when it is more treatable. At present, only 20% of patients can be operated on with curative intent, because most already have advanced disease by the time they are diagnosed, Dr. Schultz and his colleagues said.

However, the investigators emphasized that their findings are preliminary. "Further research is necessary to understand whether these microRNAs have clinical implications as a screening test for early detection of pancreatic cancer and how much this information adds to serum CA19-9," they noted.

The investigators began their search for relevant biomarkers by screening whole blood samples for the presence of any of 754 microRNAs suspected of being expressed in circulating blood by pancreatic cancers. MicroRNAs are small (17-25 nucleotides long), noncoding, single-stranded RNAs that promote oncogenesis by inhibiting the expression of tumor suppressor genes or by upregulating the expression of oncogenes. They are active in the pathogenesis, progression, and metastasis of pancreatic cancer.

The blood samples had been taken from 409 patients with histologically verified pancreatic cancer and 337 control patients, consisting of 25 patients with chronic pancreatitis and 312 healthy blood donors. Samples were drawn from the pancreatic cancer patients before they underwent any treatment; 44 had resectable tumors, and 365 had unresectable tumors.

The microRNA panels were identified and tested in a three-step process using discovery, training, and validation cohorts of patients.

In the discovery cohort, 38 microRNAs were found to have the potential to distinguish pancreatic cancer patients from other participants. Thirteen of those microRNAs were the strongest predictors and were used to develop the two diagnostic panels, which were then tested in the validation cohort.

The first diagnostic panel, termed index I, comprised 4 microRNAs, and the second panel, index II, comprised 10 microRNAs. Both panels correctly diagnosed pancreatic cancer in 85% of affected patients and correctly diagnosed chronic pancreatitis in 29% of affected patients.

Among control patients, index I correctly ruled out pancreatic disease in 48% and index II in 54%. When CA19-9 results were added to the panel results, index I correctly ruled out pancreatic disease in 98% of the control patients, and index II did so in 89%.

Thus, "the indices do achieve some separation of pancreatic cancer from healthy participants, but not a complete separation," Dr. Schultz and his associates said.

"When this microRNA biomarker study was designed in 2008, the aim was to identify microRNAs in whole blood that could identify pancreatic cancer (local, locally advanced, and metastatic) in individuals thought to be healthy," the investigators explained. "We first wanted to test the extremes (i.e., patients with known pancreatic cancer vs healthy blood donors), because if panels of microRNA could not differentiate patients with . . . high tumor burden from these healthy individuals, it would be difficult to develop a diagnostic microRNA test for patients with small tumors and low-stage cancer.

"In the future, we will assess the accuracy of indices I and II in combination with serum CA19-9 in large cohorts of patients either seen by a family physician or referred to hospitals on suspicion of cancer ... and assess whether it is possible to identify patients with pancreatic cancer at an early stage," Dr. Schultz and his associates said.

This study was supported by Herlev Hospital; the Danish Ministry of Science, Technology, and Innovation; the Danish Cancer Society; Region Hovedstadens forskinings fond til Sundhedsforskning; Aase og Ejnar Danielsens Fond; and Prosektor Axel Søeborg Ohlsen og Else Søeborg Ohlsen Mindelegat. Dr. Schultz and his associates reported holding a European patent application submitted by Copenhagen University Hospital.

Researchers have identified two novel panels of microRNAs that eventually might be used to screen patients for pancreatic cancer, distinguishing affected patients from healthy individuals and from people who have other diseases of the pancreas, particularly pancreatitis, according to a report published online Jan. 21 in JAMA.

The two microRNA panels were better than standard serum cancer antigen 19-9 (CA19-9) testing at identifying pancreatic cancer within the initial study cohort used to assess hundreds of microRNA candidates. However, CA19-9 had better diagnostic accuracy in the validation cohort used to replicate those results. Combining the results of either microRNA panel with CA19-9 offered the best diagnostic accuracy of all, said Dr. Nicolai A. Schultz, of the department of oncology, Herlev Hospital and Copenhagen University Hospital, and his associates (JAMA 2013;311:392-404).

The discovery may lead to earlier diagnosis of pancreatic cancer at a stage when it is more treatable. At present, only 20% of patients can be operated on with curative intent, because most already have advanced disease by the time they are diagnosed, Dr. Schultz and his colleagues said.

However, the investigators emphasized that their findings are preliminary. "Further research is necessary to understand whether these microRNAs have clinical implications as a screening test for early detection of pancreatic cancer and how much this information adds to serum CA19-9," they noted.

The investigators began their search for relevant biomarkers by screening whole blood samples for the presence of any of 754 microRNAs suspected of being expressed in circulating blood by pancreatic cancers. MicroRNAs are small (17-25 nucleotides long), noncoding, single-stranded RNAs that promote oncogenesis by inhibiting the expression of tumor suppressor genes or by upregulating the expression of oncogenes. They are active in the pathogenesis, progression, and metastasis of pancreatic cancer.

The blood samples had been taken from 409 patients with histologically verified pancreatic cancer and 337 control patients, consisting of 25 patients with chronic pancreatitis and 312 healthy blood donors. Samples were drawn from the pancreatic cancer patients before they underwent any treatment; 44 had resectable tumors, and 365 had unresectable tumors.

The microRNA panels were identified and tested in a three-step process using discovery, training, and validation cohorts of patients.

In the discovery cohort, 38 microRNAs were found to have the potential to distinguish pancreatic cancer patients from other participants. Thirteen of those microRNAs were the strongest predictors and were used to develop the two diagnostic panels, which were then tested in the validation cohort.

The first diagnostic panel, termed index I, comprised 4 microRNAs, and the second panel, index II, comprised 10 microRNAs. Both panels correctly diagnosed pancreatic cancer in 85% of affected patients and correctly diagnosed chronic pancreatitis in 29% of affected patients.

Among control patients, index I correctly ruled out pancreatic disease in 48% and index II in 54%. When CA19-9 results were added to the panel results, index I correctly ruled out pancreatic disease in 98% of the control patients, and index II did so in 89%.

Thus, "the indices do achieve some separation of pancreatic cancer from healthy participants, but not a complete separation," Dr. Schultz and his associates said.

"When this microRNA biomarker study was designed in 2008, the aim was to identify microRNAs in whole blood that could identify pancreatic cancer (local, locally advanced, and metastatic) in individuals thought to be healthy," the investigators explained. "We first wanted to test the extremes (i.e., patients with known pancreatic cancer vs healthy blood donors), because if panels of microRNA could not differentiate patients with . . . high tumor burden from these healthy individuals, it would be difficult to develop a diagnostic microRNA test for patients with small tumors and low-stage cancer.

"In the future, we will assess the accuracy of indices I and II in combination with serum CA19-9 in large cohorts of patients either seen by a family physician or referred to hospitals on suspicion of cancer ... and assess whether it is possible to identify patients with pancreatic cancer at an early stage," Dr. Schultz and his associates said.

This study was supported by Herlev Hospital; the Danish Ministry of Science, Technology, and Innovation; the Danish Cancer Society; Region Hovedstadens forskinings fond til Sundhedsforskning; Aase og Ejnar Danielsens Fond; and Prosektor Axel Søeborg Ohlsen og Else Søeborg Ohlsen Mindelegat. Dr. Schultz and his associates reported holding a European patent application submitted by Copenhagen University Hospital.

In an interview at the Joint Conference on the Molecular Origins of Lung Cancer, Dr. Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn., offers his perspectives on new developments in lung cancer screening and treatment, and he discusses the promise that genetically targeted approaches and immunotherapy may offer.

In an interview at the Joint Conference on the Molecular Origins of Lung Cancer, Dr. Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn., offers his perspectives on new developments in lung cancer screening and treatment, and he discusses the promise that genetically targeted approaches and immunotherapy may offer.

In an interview at the Joint Conference on the Molecular Origins of Lung Cancer, Dr. Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn., offers his perspectives on new developments in lung cancer screening and treatment, and he discusses the promise that genetically targeted approaches and immunotherapy may offer.