Luis Costa - Academia.edu (original) (raw)

Papers by Luis Costa

Several biochemical markers of bone formation and bone resorption have recently been developed. T... more Several biochemical markers of bone formation and bone resorption have recently been developed. These markers have been evaluated for clinical utility in patients with metabolic bone disease, including Paget disease and osteoporosis, and for their potential use in cancer patients whose disease has metastasized to bone. We have evaluated seven markers of bone turnover in the plasma and urine of 94 patients with newly diagnosed or progressive malignancy with and without clinical evidence of bone metastases. As determined by a positive bone scan and (or) bone survey, 30 patients had metastases to bone; 51 patients had metastatic cancer without overt bony involvement; and 13 patients had local disease without bone metastases. To evaluate the predictive value of these markers in the metastatic population, we utilized a "Z-score" and logistic regression analysis to distinguish patients with documented bone metastatic disease from those patients without clinical evidence of bone metastases. The higher the Z-score, the better the marker predicts the presence of bone metastases. With this statistical approach, urine N-telopeptide measurements had the highest Z-score and the most significant association with the probability of bone metastases. Urine deoxypyridinoline was the second most predictive marker of bone metastases. Thus, biochemical markers of bone resorption might be of use to predict the presence of bone metastases in cancer patients and to monitor the efficacy of antiresorptive therapy in patients treated for metastatic bone disease.

Seminars in Oncology, 2001

Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skel... more Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skeletal complications that are a significant cause of morbidity and mortality. Bone metastases can be difficult to diagnose radiologically and it can also be difficult to evaluate patients' response to treatment by using the methods that are currently available (radiography, bone scans, and computed axial tomography scans). These are relatively insensitive procedures, thus, there is a requirement for new methods for assessing bone response to ensure patients benefit from the optimum type and duration of treatment. Biochemical markers of bone turnover, such as N-telopeptide and the pyridinium cross-links pyridinoline and deoxypyridinoline, may provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in cancer patients who have documented evidence of metastatic bone disease. Increased levels are also observed in some patients without clinical evidence of bone metastases, when compared with normal subjects. Rises in such markers may be the first indication of bone involvement and therefore may potentially be useful in early diagnosis of progression. Preliminary data suggest bone marker level correlates with the extent of metastatic disease and the number of skeletal sites involved. Markers of bone turnover may be helpful in identifying those patients likely to respond to bisphosphonate treatment. Such markers are also potentially useful in monitoring the effectiveness of bisphosphonate therapy in the management of bone metastases, in both patients with metastatic breast disease and multiple myeloma.

Cancer, 2000

BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as brea... more BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as breast and prostate carcinoma, but they are difficult to diagnose nonradiologically, and treatment is difficult to follow clinically. Recent developments suggest that biochemical markers of bone remodeling, such as the bone collagen breakdown product N-telopeptide and the bone formation marker known as bone specific alkaline phosphatase, hold great promise as clinical tools for the management of patients with metastatic bone disease.

Seminars in Oncology, 2001

Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skel... more Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skeletal complications that are a significant cause of morbidity and mortality. Bone metastases can be difficult to diagnose radiologically and it can also be difficult to evaluate patients' response to treatment by using the methods that are currently available (radiography, bone scans, and computed axial tomography scans). These are relatively insensitive procedures, thus, there is a requirement for new methods for assessing bone response to ensure patients benefit from the optimum type and duration of treatment. Biochemical markers of bone turnover, such as N-telopeptide and the pyridinium cross-links pyridinoline and deoxypyridinoline, may provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in cancer patients who have documented evidence of metastatic bone disease. Increased levels are also observed in some patients without clinical evidence of bone metastases, when compared with normal subjects. Rises in such markers may be the first indication of bone involvement and therefore may potentially be useful in early diagnosis of progression. Preliminary data suggest bone marker level correlates with the extent of metastatic disease and the number of skeletal sites involved. Markers of bone turnover may be helpful in identifying those patients likely to respond to bisphosphonate treatment. Such markers are also potentially useful in monitoring the effectiveness of bisphosphonate therapy in the management of bone metastases, in both patients with metastatic breast disease and multiple myeloma.

The Lancet Oncology, 2014

Supportive Care in Cancer, 2008

Erratum to: Support Care CancerDOI 10.1007/s00520–008–0418–0Table 2 in this paper was published i... more Erratum to: Support Care CancerDOI 10.1007/s00520–008–0418–0Table 2 in this paper was published in error. This questionnaire is still in development, and has not been approved by the Quality of life Group of the EORTC. The published Table shows a provisional questionnaire which has not yet been validated, and which may be subject to change before approval for use in clinical studies.

Annals of Oncology, 2007

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients... more Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.

European Journal of Cancer, 1998

Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorpti... more Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorption. In cancer patients with bone metastases, NTX is more often elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts and their treatment decreases skeletal complications of malignancy. The aim of this study was to correlate urinary PYD, DPD, and NTX levels with clinical events in patients receiving pamidronate. 25 cancer patients with lytic bone disease were treated with monthly pamidronate combined with endocrine or chemotherapy; 27 others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3 and 6 months. NTX values were determined by enzyme-linked immunosorbent assay (ELISA); PYD and DPD values were determined by reverse phase high performance liquid chromatography (HPLC). Two hour urines were also collected weekly for 21 patients. The greatest diVerence as a result of pamidronate treatment was observed in NTX values. Maximum suppression was achieved 2 weeks after treatment. Of the 25 patients who received pamidronate, 21 had initially elevated NTX values. 12 of the 21 ®nished with normal NTX values, whilst 9/21 had NTX values which remained abnormally elevated. The proportions of patients with fractures between these two subgroups approached statistical signi®cance (P = 0.07) while the proportions with bony disease progression were signi®cant (P = 0.03, Fisher's exact test). Measuring NTX levels appears useful in monitoring bisphosphonate therapy of bone metastases. The goal of treatment should be to normalise NTX excretion. #

Critical Reviews in Oncology/Hematology, 2011

Critical Reviews in Oncology/Hematology, 2011

Cancer, 2000

BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as brea... more BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as breast and prostate carcinoma, but they are difficult to diagnose nonradiologically, and treatment is difficult to follow clinically. Recent developments suggest that biochemical markers of bone remodeling, such as the bone collagen breakdown product N-telopeptide and the bone formation marker known as bone specific alkaline phosphatase, hold great promise as clinical tools for the management of patients with metastatic bone disease.

Breast Cancer Research and Treatment, 2010

Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can und... more Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients' functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox-regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P \ 0.05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included. Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase. Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy.

Several biochemical markers of bone formation and bone resorption have recently been developed. T... more Several biochemical markers of bone formation and bone resorption have recently been developed. These markers have been evaluated for clinical utility in patients with metabolic bone disease, including Paget disease and osteoporosis, and for their potential use in cancer patients whose disease has metastasized to bone. We have evaluated seven markers of bone turnover in the plasma and urine of 94 patients with newly diagnosed or progressive malignancy with and without clinical evidence of bone metastases. As determined by a positive bone scan and (or) bone survey, 30 patients had metastases to bone; 51 patients had metastatic cancer without overt bony involvement; and 13 patients had local disease without bone metastases. To evaluate the predictive value of these markers in the metastatic population, we utilized a "Z-score" and logistic regression analysis to distinguish patients with documented bone metastatic disease from those patients without clinical evidence of bone metastases. The higher the Z-score, the better the marker predicts the presence of bone metastases. With this statistical approach, urine N-telopeptide measurements had the highest Z-score and the most significant association with the probability of bone metastases. Urine deoxypyridinoline was the second most predictive marker of bone metastases. Thus, biochemical markers of bone resorption might be of use to predict the presence of bone metastases in cancer patients and to monitor the efficacy of antiresorptive therapy in patients treated for metastatic bone disease.

Seminars in Oncology, 2001

Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skel... more Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skeletal complications that are a significant cause of morbidity and mortality. Bone metastases can be difficult to diagnose radiologically and it can also be difficult to evaluate patients' response to treatment by using the methods that are currently available (radiography, bone scans, and computed axial tomography scans). These are relatively insensitive procedures, thus, there is a requirement for new methods for assessing bone response to ensure patients benefit from the optimum type and duration of treatment. Biochemical markers of bone turnover, such as N-telopeptide and the pyridinium cross-links pyridinoline and deoxypyridinoline, may provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in cancer patients who have documented evidence of metastatic bone disease. Increased levels are also observed in some patients without clinical evidence of bone metastases, when compared with normal subjects. Rises in such markers may be the first indication of bone involvement and therefore may potentially be useful in early diagnosis of progression. Preliminary data suggest bone marker level correlates with the extent of metastatic disease and the number of skeletal sites involved. Markers of bone turnover may be helpful in identifying those patients likely to respond to bisphosphonate treatment. Such markers are also potentially useful in monitoring the effectiveness of bisphosphonate therapy in the management of bone metastases, in both patients with metastatic breast disease and multiple myeloma.

Cancer, 2000

BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as brea... more BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as breast and prostate carcinoma, but they are difficult to diagnose nonradiologically, and treatment is difficult to follow clinically. Recent developments suggest that biochemical markers of bone remodeling, such as the bone collagen breakdown product N-telopeptide and the bone formation marker known as bone specific alkaline phosphatase, hold great promise as clinical tools for the management of patients with metastatic bone disease.

Seminars in Oncology, 2001

Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skel... more Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skeletal complications that are a significant cause of morbidity and mortality. Bone metastases can be difficult to diagnose radiologically and it can also be difficult to evaluate patients' response to treatment by using the methods that are currently available (radiography, bone scans, and computed axial tomography scans). These are relatively insensitive procedures, thus, there is a requirement for new methods for assessing bone response to ensure patients benefit from the optimum type and duration of treatment. Biochemical markers of bone turnover, such as N-telopeptide and the pyridinium cross-links pyridinoline and deoxypyridinoline, may provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in cancer patients who have documented evidence of metastatic bone disease. Increased levels are also observed in some patients without clinical evidence of bone metastases, when compared with normal subjects. Rises in such markers may be the first indication of bone involvement and therefore may potentially be useful in early diagnosis of progression. Preliminary data suggest bone marker level correlates with the extent of metastatic disease and the number of skeletal sites involved. Markers of bone turnover may be helpful in identifying those patients likely to respond to bisphosphonate treatment. Such markers are also potentially useful in monitoring the effectiveness of bisphosphonate therapy in the management of bone metastases, in both patients with metastatic breast disease and multiple myeloma.

The Lancet Oncology, 2014

Supportive Care in Cancer, 2008

Erratum to: Support Care CancerDOI 10.1007/s00520–008–0418–0Table 2 in this paper was published i... more Erratum to: Support Care CancerDOI 10.1007/s00520–008–0418–0Table 2 in this paper was published in error. This questionnaire is still in development, and has not been approved by the Quality of life Group of the EORTC. The published Table shows a provisional questionnaire which has not yet been validated, and which may be subject to change before approval for use in clinical studies.

Annals of Oncology, 2007

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients... more Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.

European Journal of Cancer, 1998

Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorpti... more Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorption. In cancer patients with bone metastases, NTX is more often elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts and their treatment decreases skeletal complications of malignancy. The aim of this study was to correlate urinary PYD, DPD, and NTX levels with clinical events in patients receiving pamidronate. 25 cancer patients with lytic bone disease were treated with monthly pamidronate combined with endocrine or chemotherapy; 27 others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3 and 6 months. NTX values were determined by enzyme-linked immunosorbent assay (ELISA); PYD and DPD values were determined by reverse phase high performance liquid chromatography (HPLC). Two hour urines were also collected weekly for 21 patients. The greatest diVerence as a result of pamidronate treatment was observed in NTX values. Maximum suppression was achieved 2 weeks after treatment. Of the 25 patients who received pamidronate, 21 had initially elevated NTX values. 12 of the 21 ®nished with normal NTX values, whilst 9/21 had NTX values which remained abnormally elevated. The proportions of patients with fractures between these two subgroups approached statistical signi®cance (P = 0.07) while the proportions with bony disease progression were signi®cant (P = 0.03, Fisher's exact test). Measuring NTX levels appears useful in monitoring bisphosphonate therapy of bone metastases. The goal of treatment should be to normalise NTX excretion. #

Critical Reviews in Oncology/Hematology, 2011

Critical Reviews in Oncology/Hematology, 2011

Cancer, 2000

BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as brea... more BACKGROUND. Skeletal metastases are common occurrences in patients with malignancies such as breast and prostate carcinoma, but they are difficult to diagnose nonradiologically, and treatment is difficult to follow clinically. Recent developments suggest that biochemical markers of bone remodeling, such as the bone collagen breakdown product N-telopeptide and the bone formation marker known as bone specific alkaline phosphatase, hold great promise as clinical tools for the management of patients with metastatic bone disease.

Breast Cancer Research and Treatment, 2010

Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can und... more Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients' functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox-regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P \ 0.05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included. Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase. Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy.