MD

Cabozantinib in metastatic prostate cancer^1,2

Researchers tested cabozantinib, a tyrosine-kinase inhibitor (TKI) against MET and vascular endothelial growth factor receptor 2 (VEGF), in a large phase 2 randomized discontinuation trial in 9 tumor types. A subset of 171 patients with castrateresistant prostate cancer (CRPC) was reported in this study. Patients were treated on open label for 12 weeks, and then if stable, were randomized to receive the active drug or placebo. The trial was suspended early by the study oversight committee because: a) Cabozantinib was too toxic for the study to continue. b) The prostate-specific antigen (PSA) level fell in most of the treated patients. c) In the initial 121 patients, there was an unexpected improvement in bone scans and decrease in pain in the lead-in stage of the study. d) Unexpected rapid soft tissue progression. Bone scans improved in 78% of patients, and in 12% there was complete remission. After further analysis, the following were true except for: a) Cabozantinib interfered with technetium-99, and thus, the responses were not real, but rather an artifact. b) The PSA did not correlate with improvement in bone pain. c) Markers of bone formation and resorption showed improvement, and there was no correlation with prior bisphosphonate therapy. d) Bone scan improvement correlated with improvement in soft tissue disease. 

Key points

The results in patients with prostate cancer were so striking – 72% of patients had regression in soft tissue lesions, and 68% of evaluable patients had improvement on bone scan, including complete resolution in 12% – that the subset analysis was published as a rapid communication.1,2 Because of very high response rates (5% at 12 weeks) and symptomatic improvement in the initial 122 patients who were enrolled, random assignment was discontinued. Bone markers improved in concert with the radiologic and clinical improvement. Answers c, a

Cabozantinib in metastatic prostate cancer^1,2

Researchers tested cabozantinib, a tyrosine-kinase inhibitor (TKI) against MET and vascular endothelial growth factor receptor 2 (VEGF), in a large phase 2 randomized discontinuation trial in 9 tumor types. A subset of 171 patients with castrateresistant prostate cancer (CRPC) was reported in this study. Patients were treated on open label for 12 weeks, and then if stable, were randomized to receive the active drug or placebo. The trial was suspended early by the study oversight committee because: a) Cabozantinib was too toxic for the study to continue. b) The prostate-specific antigen (PSA) level fell in most of the treated patients. c) In the initial 121 patients, there was an unexpected improvement in bone scans and decrease in pain in the lead-in stage of the study. d) Unexpected rapid soft tissue progression. Bone scans improved in 78% of patients, and in 12% there was complete remission. After further analysis, the following were true except for: a) Cabozantinib interfered with technetium-99, and thus, the responses were not real, but rather an artifact. b) The PSA did not correlate with improvement in bone pain. c) Markers of bone formation and resorption showed improvement, and there was no correlation with prior bisphosphonate therapy. d) Bone scan improvement correlated with improvement in soft tissue disease. 

Key points

The results in patients with prostate cancer were so striking – 72% of patients had regression in soft tissue lesions, and 68% of evaluable patients had improvement on bone scan, including complete resolution in 12% – that the subset analysis was published as a rapid communication.1,2 Because of very high response rates (5% at 12 weeks) and symptomatic improvement in the initial 122 patients who were enrolled, random assignment was discontinued. Bone markers improved in concert with the radiologic and clinical improvement. Answers c, a

Cabozantinib in metastatic prostate cancer^1,2

Researchers tested cabozantinib, a tyrosine-kinase inhibitor (TKI) against MET and vascular endothelial growth factor receptor 2 (VEGF), in a large phase 2 randomized discontinuation trial in 9 tumor types. A subset of 171 patients with castrateresistant prostate cancer (CRPC) was reported in this study. Patients were treated on open label for 12 weeks, and then if stable, were randomized to receive the active drug or placebo. The trial was suspended early by the study oversight committee because: a) Cabozantinib was too toxic for the study to continue. b) The prostate-specific antigen (PSA) level fell in most of the treated patients. c) In the initial 121 patients, there was an unexpected improvement in bone scans and decrease in pain in the lead-in stage of the study. d) Unexpected rapid soft tissue progression. Bone scans improved in 78% of patients, and in 12% there was complete remission. After further analysis, the following were true except for: a) Cabozantinib interfered with technetium-99, and thus, the responses were not real, but rather an artifact. b) The PSA did not correlate with improvement in bone pain. c) Markers of bone formation and resorption showed improvement, and there was no correlation with prior bisphosphonate therapy. d) Bone scan improvement correlated with improvement in soft tissue disease. 

Key points

The results in patients with prostate cancer were so striking – 72% of patients had regression in soft tissue lesions, and 68% of evaluable patients had improvement on bone scan, including complete resolution in 12% – that the subset analysis was published as a rapid communication.1,2 Because of very high response rates (5% at 12 weeks) and symptomatic improvement in the initial 122 patients who were enrolled, random assignment was discontinued. Bone markers improved in concert with the radiologic and clinical improvement. Answers c, a

The stories of patients and families, like this one presented by Kimberly Lastinger, offer powerful lessons for health professionals about the human experience of illness and its impact on the person and family. Furthermore, patient narratives present ‘experiential truth and passion’ that compel us to re-examine medical practices and ethical perceptions of care.¹ However much we think we know from our years of medical practice and our observation of many patients and families, we are not ‘in the patient’s shoes’. The content of patient narratives supports ethical decisions by helping us listen and hear what patients say, how they say it, and by clarifying why it matters. The patient story can help us focus healthcare on the patient and to recognize that the patient is the ultimate authority when it comes to the interpretation of his or her illness experience. Until one has been there, it is impossible to imagine the impact of a life-threatening illness. I am reminded of my own surprise at seeing, feeling, and experiencing the loss of a loved one to cancer. I have been a medical oncologist and palliative care physician for more than 25 years, and I thought I understood the experience I could expect when my husband died. Instead, I was stunned to find that I didn’t have a clue! It has taught me to listen more carefully and ask more questions. When listening occurs, understanding increases, and narratives can be jointly constructed by the patient and healthcare provider. This leads to power that is shared and the sharing of power constitutes an important ethical safeguard within the relationship.²

The narrative presented here suggests a remarkably positive experience of a devastating illness and its potential impact on the patient and family. The patient was someone with tremendous resiliency and optimism. She was commited to living on her terms and for caring for her daughter. Her story is an inspiring one. Ms Lastinger recalls her mother’s amazing support system, but also her mother’s fear of dying. The latter learned only years after her mother’s death from reading her journal. I wonder if, as too often happens, we failed to offer adequate psychosocial support. This service is too often not offered.^3,4 This occurs for many reasons including, I suspect, when there is the perception of a supportive social network embracing the patient. It behooves us as healthcare professionals to remember that patients may not want or be able to share some of their deepest fears, the threat of dying or of being dependent, with the people they love. The patients who seem to be doing well emotionally, those with ‘great support’ may also benefit from professional counseling.

The stories of patients and families, like this one presented by Kimberly Lastinger, offer powerful lessons for health professionals about the human experience of illness and its impact on the person and family. Furthermore, patient narratives present ‘experiential truth and passion’ that compel us to re-examine medical practices and ethical perceptions of care.¹ However much we think we know from our years of medical practice and our observation of many patients and families, we are not ‘in the patient’s shoes’. The content of patient narratives supports ethical decisions by helping us listen and hear what patients say, how they say it, and by clarifying why it matters. The patient story can help us focus healthcare on the patient and to recognize that the patient is the ultimate authority when it comes to the interpretation of his or her illness experience. Until one has been there, it is impossible to imagine the impact of a life-threatening illness. I am reminded of my own surprise at seeing, feeling, and experiencing the loss of a loved one to cancer. I have been a medical oncologist and palliative care physician for more than 25 years, and I thought I understood the experience I could expect when my husband died. Instead, I was stunned to find that I didn’t have a clue! It has taught me to listen more carefully and ask more questions. When listening occurs, understanding increases, and narratives can be jointly constructed by the patient and healthcare provider. This leads to power that is shared and the sharing of power constitutes an important ethical safeguard within the relationship.²

The narrative presented here suggests a remarkably positive experience of a devastating illness and its potential impact on the patient and family. The patient was someone with tremendous resiliency and optimism. She was commited to living on her terms and for caring for her daughter. Her story is an inspiring one. Ms Lastinger recalls her mother’s amazing support system, but also her mother’s fear of dying. The latter learned only years after her mother’s death from reading her journal. I wonder if, as too often happens, we failed to offer adequate psychosocial support. This service is too often not offered.^3,4 This occurs for many reasons including, I suspect, when there is the perception of a supportive social network embracing the patient. It behooves us as healthcare professionals to remember that patients may not want or be able to share some of their deepest fears, the threat of dying or of being dependent, with the people they love. The patients who seem to be doing well emotionally, those with ‘great support’ may also benefit from professional counseling.

The stories of patients and families, like this one presented by Kimberly Lastinger, offer powerful lessons for health professionals about the human experience of illness and its impact on the person and family. Furthermore, patient narratives present ‘experiential truth and passion’ that compel us to re-examine medical practices and ethical perceptions of care.¹ However much we think we know from our years of medical practice and our observation of many patients and families, we are not ‘in the patient’s shoes’. The content of patient narratives supports ethical decisions by helping us listen and hear what patients say, how they say it, and by clarifying why it matters. The patient story can help us focus healthcare on the patient and to recognize that the patient is the ultimate authority when it comes to the interpretation of his or her illness experience. Until one has been there, it is impossible to imagine the impact of a life-threatening illness. I am reminded of my own surprise at seeing, feeling, and experiencing the loss of a loved one to cancer. I have been a medical oncologist and palliative care physician for more than 25 years, and I thought I understood the experience I could expect when my husband died. Instead, I was stunned to find that I didn’t have a clue! It has taught me to listen more carefully and ask more questions. When listening occurs, understanding increases, and narratives can be jointly constructed by the patient and healthcare provider. This leads to power that is shared and the sharing of power constitutes an important ethical safeguard within the relationship.²

The narrative presented here suggests a remarkably positive experience of a devastating illness and its potential impact on the patient and family. The patient was someone with tremendous resiliency and optimism. She was commited to living on her terms and for caring for her daughter. Her story is an inspiring one. Ms Lastinger recalls her mother’s amazing support system, but also her mother’s fear of dying. The latter learned only years after her mother’s death from reading her journal. I wonder if, as too often happens, we failed to offer adequate psychosocial support. This service is too often not offered.^3,4 This occurs for many reasons including, I suspect, when there is the perception of a supportive social network embracing the patient. It behooves us as healthcare professionals to remember that patients may not want or be able to share some of their deepest fears, the threat of dying or of being dependent, with the people they love. The patients who seem to be doing well emotionally, those with ‘great support’ may also benefit from professional counseling.

Squamous cell carcinomas of the head and neck account for 3% of all new cancers diagnosed annually within the United States.¹ According to the Surveillance Epidemiology
and Ends Reports (SEER) database, 79% of patients in the US present with local or regional advanced disease and are treated with combinedmodality therapy.² Factors that influence treatment decision making include the following: resectability, function preservation, local patterns of care, and patient characteristics or preferences. In this cohort of patients, disease eradication is the goal of therapy. Conversely, for approximately 16% of patients who are diagnosed with metastatic disease at presentation, or the substantial portion of patients who develop non-curable disease recurrence, the main therapeutic objectives are palliation and prolongation of survival (accessible at http://seer.cancer.gov/statfacts/html/oralcav.html).^2,3 We define patients as having non-curable recurrence if development of metastatic disease or development of local recurrence is not amenable to either surgical resection or re-irradiation therapy. Several changes in the epidemiology and treatment of metastatic and recurrent head and neck cancer (M/RHNC) have resulted in paradigm shifts that effect treatment decision making in this population. First, a combination of standard chemotherapy with cetuximab has demonstrated a survival advantage. This is the first time that any agent or combination of agents has demonstrated superiority in the treatment of M/RHNC.⁴ Second, human papilloma virus (HPV)-associated oropharyngeal cancers are epidemic in many areas of the world. The cohort of HPV-positive patients has an excellent prognosis with currently available primary treatment regimens. The recurrence rate in this population is low; however, data regarding the treatment responsiveness of HPV-associated tumors that recur after primary therapy is lacking. Finally, with the increased use of aggressive combined modality regimens as primary therapy, patients with recurrent disease are often heavily pretreated and suffer from symptoms secondary to their initial therapy. It is important to understand how the evolving epidemiology and treatment paradigms affect decision making for our patients. This requires an understanding of how these changes affect both the benefits and risks to the patient.

Squamous cell carcinomas of the head and neck account for 3% of all new cancers diagnosed annually within the United States.¹ According to the Surveillance Epidemiology
and Ends Reports (SEER) database, 79% of patients in the US present with local or regional advanced disease and are treated with combinedmodality therapy.² Factors that influence treatment decision making include the following: resectability, function preservation, local patterns of care, and patient characteristics or preferences. In this cohort of patients, disease eradication is the goal of therapy. Conversely, for approximately 16% of patients who are diagnosed with metastatic disease at presentation, or the substantial portion of patients who develop non-curable disease recurrence, the main therapeutic objectives are palliation and prolongation of survival (accessible at http://seer.cancer.gov/statfacts/html/oralcav.html).^2,3 We define patients as having non-curable recurrence if development of metastatic disease or development of local recurrence is not amenable to either surgical resection or re-irradiation therapy. Several changes in the epidemiology and treatment of metastatic and recurrent head and neck cancer (M/RHNC) have resulted in paradigm shifts that effect treatment decision making in this population. First, a combination of standard chemotherapy with cetuximab has demonstrated a survival advantage. This is the first time that any agent or combination of agents has demonstrated superiority in the treatment of M/RHNC.⁴ Second, human papilloma virus (HPV)-associated oropharyngeal cancers are epidemic in many areas of the world. The cohort of HPV-positive patients has an excellent prognosis with currently available primary treatment regimens. The recurrence rate in this population is low; however, data regarding the treatment responsiveness of HPV-associated tumors that recur after primary therapy is lacking. Finally, with the increased use of aggressive combined modality regimens as primary therapy, patients with recurrent disease are often heavily pretreated and suffer from symptoms secondary to their initial therapy. It is important to understand how the evolving epidemiology and treatment paradigms affect decision making for our patients. This requires an understanding of how these changes affect both the benefits and risks to the patient.

Squamous cell carcinomas of the head and neck account for 3% of all new cancers diagnosed annually within the United States.¹ According to the Surveillance Epidemiology
and Ends Reports (SEER) database, 79% of patients in the US present with local or regional advanced disease and are treated with combinedmodality therapy.² Factors that influence treatment decision making include the following: resectability, function preservation, local patterns of care, and patient characteristics or preferences. In this cohort of patients, disease eradication is the goal of therapy. Conversely, for approximately 16% of patients who are diagnosed with metastatic disease at presentation, or the substantial portion of patients who develop non-curable disease recurrence, the main therapeutic objectives are palliation and prolongation of survival (accessible at http://seer.cancer.gov/statfacts/html/oralcav.html).^2,3 We define patients as having non-curable recurrence if development of metastatic disease or development of local recurrence is not amenable to either surgical resection or re-irradiation therapy. Several changes in the epidemiology and treatment of metastatic and recurrent head and neck cancer (M/RHNC) have resulted in paradigm shifts that effect treatment decision making in this population. First, a combination of standard chemotherapy with cetuximab has demonstrated a survival advantage. This is the first time that any agent or combination of agents has demonstrated superiority in the treatment of M/RHNC.⁴ Second, human papilloma virus (HPV)-associated oropharyngeal cancers are epidemic in many areas of the world. The cohort of HPV-positive patients has an excellent prognosis with currently available primary treatment regimens. The recurrence rate in this population is low; however, data regarding the treatment responsiveness of HPV-associated tumors that recur after primary therapy is lacking. Finally, with the increased use of aggressive combined modality regimens as primary therapy, patients with recurrent disease are often heavily pretreated and suffer from symptoms secondary to their initial therapy. It is important to understand how the evolving epidemiology and treatment paradigms affect decision making for our patients. This requires an understanding of how these changes affect both the benefits and risks to the patient.

Palliative care quality indicators should be part of oncology performance assessment initiatives. Palliative care programs should also include initiatives to address the overall quality of palliative care issues, such as pain management, in the settings where the programs are located.1 Measuring quality facilitates justifying palliative care initiatives and documenting their impact, targeting quality improvement efforts, monitoring care for deficiencies, and evaluating providers (Table 1). However, measurement in this field is often not straightforward. Potential challenges include defining the population to measure and data sources, collection and analysis, as well as choosing among many potentially relevant issues and quality measures. This article describes an approach to quality measurement in palliative care, beginning with a description of key frameworks to guide the measurement approach. The article also reviews key steps in designing a quality measurement program, which include defining the quality problem and population to measure and choosing domains and specific measures. Finally, the article addresses other key considerations, such as considering unintended consequences and using data for quality improvement.

Frameworks for evaluating quality

The Donabedian framework of structure (stable elements of the health care system), process (what health care services are provided), and outcome (end results for the patient and family) can be
applied to relevant domains to guide evaluation design (Table 2).^2-8 Key structural elements may include characteristics of programs (eg, palliative clinic availability), providers (eg, multidisciplinary members of the palliative care team), and tools (eg, do-not-resuscitate policies). Processes may include technical aspects of care, such as appropriate prescribing and interpersonal aspects of care (eg, coordination among providers). Outcomes may include patient quality of life or symptoms, perceptions of care, or caregiver outcomes such as burden. Outcomes may also be categorized as overuse (eg, use of chemotherapy at the end of life compared to national benchmarks), underuse (eg, lower rates of hospice care or use of antinausea drugs), or appropriateness of care (eg, accurately documenting patients’ preferences for care).

Palliative care quality indicators should be part of oncology performance assessment initiatives. Palliative care programs should also include initiatives to address the overall quality of palliative care issues, such as pain management, in the settings where the programs are located.1 Measuring quality facilitates justifying palliative care initiatives and documenting their impact, targeting quality improvement efforts, monitoring care for deficiencies, and evaluating providers (Table 1). However, measurement in this field is often not straightforward. Potential challenges include defining the population to measure and data sources, collection and analysis, as well as choosing among many potentially relevant issues and quality measures. This article describes an approach to quality measurement in palliative care, beginning with a description of key frameworks to guide the measurement approach. The article also reviews key steps in designing a quality measurement program, which include defining the quality problem and population to measure and choosing domains and specific measures. Finally, the article addresses other key considerations, such as considering unintended consequences and using data for quality improvement.

Frameworks for evaluating quality

The Donabedian framework of structure (stable elements of the health care system), process (what health care services are provided), and outcome (end results for the patient and family) can be
applied to relevant domains to guide evaluation design (Table 2).^2-8 Key structural elements may include characteristics of programs (eg, palliative clinic availability), providers (eg, multidisciplinary members of the palliative care team), and tools (eg, do-not-resuscitate policies). Processes may include technical aspects of care, such as appropriate prescribing and interpersonal aspects of care (eg, coordination among providers). Outcomes may include patient quality of life or symptoms, perceptions of care, or caregiver outcomes such as burden. Outcomes may also be categorized as overuse (eg, use of chemotherapy at the end of life compared to national benchmarks), underuse (eg, lower rates of hospice care or use of antinausea drugs), or appropriateness of care (eg, accurately documenting patients’ preferences for care).

Palliative care quality indicators should be part of oncology performance assessment initiatives. Palliative care programs should also include initiatives to address the overall quality of palliative care issues, such as pain management, in the settings where the programs are located.1 Measuring quality facilitates justifying palliative care initiatives and documenting their impact, targeting quality improvement efforts, monitoring care for deficiencies, and evaluating providers (Table 1). However, measurement in this field is often not straightforward. Potential challenges include defining the population to measure and data sources, collection and analysis, as well as choosing among many potentially relevant issues and quality measures. This article describes an approach to quality measurement in palliative care, beginning with a description of key frameworks to guide the measurement approach. The article also reviews key steps in designing a quality measurement program, which include defining the quality problem and population to measure and choosing domains and specific measures. Finally, the article addresses other key considerations, such as considering unintended consequences and using data for quality improvement.

Frameworks for evaluating quality

The Donabedian framework of structure (stable elements of the health care system), process (what health care services are provided), and outcome (end results for the patient and family) can be
applied to relevant domains to guide evaluation design (Table 2).^2-8 Key structural elements may include characteristics of programs (eg, palliative clinic availability), providers (eg, multidisciplinary members of the palliative care team), and tools (eg, do-not-resuscitate policies). Processes may include technical aspects of care, such as appropriate prescribing and interpersonal aspects of care (eg, coordination among providers). Outcomes may include patient quality of life or symptoms, perceptions of care, or caregiver outcomes such as burden. Outcomes may also be categorized as overuse (eg, use of chemotherapy at the end of life compared to national benchmarks), underuse (eg, lower rates of hospice care or use of antinausea drugs), or appropriateness of care (eg, accurately documenting patients’ preferences for care).

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.