The Food and Drug Administration has updated the labels on certain HIV drugs to include a contraindication for lurasidone (Latuda), an antipsychotic medication.

Lurasidone is used to treat depressive episodes in bipolar I disorder (bipolar depression) and schizophrenia in adults. The contraindication was added because of “the potential for serious and/or life-threatening reactions,” according to the FDA.

The labels on the following pharmaceutical products will be updated to reflect the change:

Aptivus (tipranavir)

Crixivan (indinavir)

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide)

Invirase (saquinavir)

Kaletra (lopinavir/ritonavir)

Lexiva (fosamprenavir): Lurasidone is contraindicated because of the potential for serious and/or life-threatening reactions if fosamprenavir is coadministered with ritonavir.

Norvir (ritonavir)

Prezista (darunavir)

Reyataz (atazanavir): Lurasidone is contraindicated because of the potential for serious and/or life-threatening reactions if atazanavir is coadministered with ritonavir.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate)

Viracept (nelfinavir)

Labels for Evotaz (atazanavir/cobicistat) and Prezcobix (darunavir/cobicistat) already include a contraindication for lurasidone, the FDA announcement noted.

[email protected]

On Twitter @richpizzi

The Food and Drug Administration has updated the labels on certain HIV drugs to include a contraindication for lurasidone (Latuda), an antipsychotic medication.

Lurasidone is used to treat depressive episodes in bipolar I disorder (bipolar depression) and schizophrenia in adults. The contraindication was added because of “the potential for serious and/or life-threatening reactions,” according to the FDA.

The labels on the following pharmaceutical products will be updated to reflect the change:

Aptivus (tipranavir)

Crixivan (indinavir)

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide)

Invirase (saquinavir)

Kaletra (lopinavir/ritonavir)

Lexiva (fosamprenavir): Lurasidone is contraindicated because of the potential for serious and/or life-threatening reactions if fosamprenavir is coadministered with ritonavir.

Norvir (ritonavir)

Prezista (darunavir)

Reyataz (atazanavir): Lurasidone is contraindicated because of the potential for serious and/or life-threatening reactions if atazanavir is coadministered with ritonavir.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate)

Viracept (nelfinavir)

Labels for Evotaz (atazanavir/cobicistat) and Prezcobix (darunavir/cobicistat) already include a contraindication for lurasidone, the FDA announcement noted.

[email protected]

On Twitter @richpizzi

The Food and Drug Administration has updated the labels on certain HIV drugs to include a contraindication for lurasidone (Latuda), an antipsychotic medication.

Lurasidone is used to treat depressive episodes in bipolar I disorder (bipolar depression) and schizophrenia in adults. The contraindication was added because of “the potential for serious and/or life-threatening reactions,” according to the FDA.

The labels on the following pharmaceutical products will be updated to reflect the change:

Aptivus (tipranavir)

Crixivan (indinavir)

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide)

Invirase (saquinavir)

Kaletra (lopinavir/ritonavir)

Lexiva (fosamprenavir): Lurasidone is contraindicated because of the potential for serious and/or life-threatening reactions if fosamprenavir is coadministered with ritonavir.

Norvir (ritonavir)

Prezista (darunavir)

Reyataz (atazanavir): Lurasidone is contraindicated because of the potential for serious and/or life-threatening reactions if atazanavir is coadministered with ritonavir.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate)

Viracept (nelfinavir)

Labels for Evotaz (atazanavir/cobicistat) and Prezcobix (darunavir/cobicistat) already include a contraindication for lurasidone, the FDA announcement noted.

[email protected]

On Twitter @richpizzi

SAN DIEGO – As the number of surgery patients over the age of 65 continues to burgeon, clinicians have a resource to help them provide optimal perioperative care to this patient population.

At the American College of Surgeons/National Surgical Quality Improvement Program National Conference, Ronnie A. Rosenthal, MD, discussed highlights from “Optimal Perioperative Management of the Geriatric Patient: A Best Practice Guideline from the ACS NSQIP/American Geriatrics Society,” which was published in January 2016.

Work on the guideline began in 2013, when a 28-member multidisciplinary panel began to conduct a structured search of Medline to identify systematic reviews, meta-analyses, practice guidelines, and clinical trials on the topic. The panel included experts from ACS, the ACS Geriatric Surgery Task Force, the American Society of Anesthesiologists, the American Geriatrics Society, and the AGS’ Geriatrics for Specialists Initiative. The 61-page document is divided into four categories: immediate preoperative period, intraoperative management, postoperative care, and care transitions.

Working with patients on goals

As noted in the guideline, a primary goal of the immediate preoperative period is to discuss with the patient his or her goals and expectations. Patient expectations are influenced by their treatment preferences. In fact, researchers have found that older patients are less likely to want a treatment – even if it results in cure – that may result in severe functional or cognitive impairment. For patients with existing advanced directives, organizations representing nurses, anesthesiologists, and surgeons all agree that there must be a “reconsideration” of these directives prior to surgery. A discussion that includes the new risks of the procedure must be conducted to ensure that the approach to potential life-threatening problems is consistent with the patient’s values.

Preoperative management of medications

Another recommendation for the preoperative period is to ensure that older patients have shorter fasts, have appropriate prophylactic antibiotics, continue medications with withdrawal potential, and discontinue medications that are not essential. The latter point is based on the Beers Criteria, a list of medications that are inappropriate or potentially inappropriate to use in older adults (J Am Geriatr Soc. 2015 Nov;63[11]:2227-46). “You want to discontinue as many inappropriate medications as possible, because one of the main side effects of their use is delirium, and you want to avoid that,” said Dr. Rosenthal, professor of surgery at the Yale University, New Haven, Conn., and one of the guideline authors.

©Thinkstockphotos.com

Anesthesia and pain management

Intraoperative management strategies contained in the guideline include establishing an anesthetic approach and a perioperative analgesia pain plan, preventing postoperative nausea and vomiting, assessing patient safety in the OR, preventing predictable complications, and optimizing fluid management. Physiologic effects of anesthesia medications include changes in systemic vascular resistance, cardiac preload, baroreceptor responses, lung mechanics, oxygen diffusion, neurotransmitter function, and end-organ blood flow, among others. “These physiologic changes of aging have significant clinical implications,” Dr. Rosenthal noted. “These are variable among individuals and variable among organ systems, and it’s important that we pay attention to that. Because of this variability, there is insufficient evidence to recommend a single ‘best’ anesthetic plan for all older adults.”

The guideline recommends that each patient have an individualized pain plan that consists of a directed pain history and physical exam and is appropriately titrated for increased sensitivity. “It should include a prophylactic bowel regimen for anybody who’s on an opioid in particular,” she said. “We should avoid inappropriate medications like benzodiazepines, and we should use a multimodal therapy with opioid-sparing and regional techniques.”

Pulmonary considerations for anesthesia include susceptibility to hypocarbia and hypoxemia, and susceptibility to residual anesthetic effects. “Because of physiologic changes, the anesthesia medications aren’t metabolized in the same way,” she said. “Older people may have lower drug requirements and may not recover as quickly from the effects of these drugs. This can lead to respiratory compromise and also can increase the risk of aspiration.” Strategies to prevent pulmonary complications include using regional anesthesia when possible and avoiding the use of intermediate- and long-acting neuromuscular blocking agents. Dr. Rosenthal said that there is insufficient evidence in the current medical literature to recommend a single “best” intraoperative fluid management plan for all older adults. “Part of the reason it’s so difficult is because of the cardiac physiologic changes [with aging],” she explained. “Older people are susceptible to volume overload. On the other hand, they also may have an exaggerated decline in cardiac function if you give them too little fluid and they have insufficient preload. It’s a very fine line and that’s why it’s hard to recommend a single best strategy.”

Be alert to postoperative delirium

Postoperatively, the guideline recommends that care plans include controlling perioperative acute pain; addressing delirium/cognitive issues; preventing functional decline, falls, pressure ulcers, and urinary track infections; maintaining adequate nutrition; and avoiding pulmonary complications. Dr. Rosenthal underscored the importance of using the four-question Short Confusion Assessment Method (Short CAM) to assess for delirium. “For it to be delirium, there has to be evidence of acute change in mental status from baseline; it has to be acute and fluctuating, and characterized by inattention,” she said. “The patient also has to have either disorganized thinking or an altered level of consciousness.”

Many of the precipitating factors of delirium can be prevented by treating pain, watching medications, preventing dehydration and undernutrition, removing catheters and other devices when possible, preventing constipation, and using minimally invasive techniques to reduce the physiologic stress of surgery. “Sometimes symptoms of delirium are a warning sign that something else is going on, such as an infection, hypoxemia, electrolyte imbalance, neurological events, and major organ dysfunction,” she said. The first-line therapy for treating delirium as recommended in the guideline is a multicomponent intervention that focuses on frequent reorientation with voice, calendars, and clocks; eliminating use of restraints; having familiar objects in the room; and ensuring the use of assistive devices. The second-line therapy is antipsychotic medications at the lowest effective dose. “The mantra is start low and go slow,” she said.

Preventing postoperative functional decline

Another postoperative strategy in the guideline involves targeted fall prevention, such as having an assistive device at the bedside if used as an outpatient and prescribing early physical therapy focused on maintaining mobility as the primary event. “Every day an older patient is immobilized it takes at least 3 days to regain the lost function,” Dr. Rosenthal said. “And for older surgical patients, one in four experiences a significant decline in function by hospital discharge and 60% experience some loss of independence.” (The latter statistic comes from a study published online July 13, 2016, in JAMA Surgery: doi:10.1001/jamasurg.2016.1689.) Interventions for preventing functional decline include promotion of family participation in care, early mobilization, early physical/occupational therapy referral, geriatric consultation, comprehensive discharge planning, and nutritional support. She pointed out that an estimated 40% of community-dwelling elders and two-thirds of nursing home residents are either malnourished or “at risk” of malnutrition.

Transition of care

The final category in the guideline, transition of care, recommends an assessment of social support/home health needs, complete medication review, predischarge geriatric assessment, formal written discharge instructions, and communication with the patient’s primary care physician. “Common models of transitional care involve good coordination with the primary care physician,” she said. “There’s good data to show that people who see their primary care physician within 2 weeks of discharge do better in terms of readmission.”

Dr. Rosenthal reported having no financial disclosures.

[email protected]

SAN DIEGO – As the number of surgery patients over the age of 65 continues to burgeon, clinicians have a resource to help them provide optimal perioperative care to this patient population.

At the American College of Surgeons/National Surgical Quality Improvement Program National Conference, Ronnie A. Rosenthal, MD, discussed highlights from “Optimal Perioperative Management of the Geriatric Patient: A Best Practice Guideline from the ACS NSQIP/American Geriatrics Society,” which was published in January 2016.

Work on the guideline began in 2013, when a 28-member multidisciplinary panel began to conduct a structured search of Medline to identify systematic reviews, meta-analyses, practice guidelines, and clinical trials on the topic. The panel included experts from ACS, the ACS Geriatric Surgery Task Force, the American Society of Anesthesiologists, the American Geriatrics Society, and the AGS’ Geriatrics for Specialists Initiative. The 61-page document is divided into four categories: immediate preoperative period, intraoperative management, postoperative care, and care transitions.

Working with patients on goals

As noted in the guideline, a primary goal of the immediate preoperative period is to discuss with the patient his or her goals and expectations. Patient expectations are influenced by their treatment preferences. In fact, researchers have found that older patients are less likely to want a treatment – even if it results in cure – that may result in severe functional or cognitive impairment. For patients with existing advanced directives, organizations representing nurses, anesthesiologists, and surgeons all agree that there must be a “reconsideration” of these directives prior to surgery. A discussion that includes the new risks of the procedure must be conducted to ensure that the approach to potential life-threatening problems is consistent with the patient’s values.

Preoperative management of medications

Another recommendation for the preoperative period is to ensure that older patients have shorter fasts, have appropriate prophylactic antibiotics, continue medications with withdrawal potential, and discontinue medications that are not essential. The latter point is based on the Beers Criteria, a list of medications that are inappropriate or potentially inappropriate to use in older adults (J Am Geriatr Soc. 2015 Nov;63[11]:2227-46). “You want to discontinue as many inappropriate medications as possible, because one of the main side effects of their use is delirium, and you want to avoid that,” said Dr. Rosenthal, professor of surgery at the Yale University, New Haven, Conn., and one of the guideline authors.

©Thinkstockphotos.com

Anesthesia and pain management

Intraoperative management strategies contained in the guideline include establishing an anesthetic approach and a perioperative analgesia pain plan, preventing postoperative nausea and vomiting, assessing patient safety in the OR, preventing predictable complications, and optimizing fluid management. Physiologic effects of anesthesia medications include changes in systemic vascular resistance, cardiac preload, baroreceptor responses, lung mechanics, oxygen diffusion, neurotransmitter function, and end-organ blood flow, among others. “These physiologic changes of aging have significant clinical implications,” Dr. Rosenthal noted. “These are variable among individuals and variable among organ systems, and it’s important that we pay attention to that. Because of this variability, there is insufficient evidence to recommend a single ‘best’ anesthetic plan for all older adults.”

The guideline recommends that each patient have an individualized pain plan that consists of a directed pain history and physical exam and is appropriately titrated for increased sensitivity. “It should include a prophylactic bowel regimen for anybody who’s on an opioid in particular,” she said. “We should avoid inappropriate medications like benzodiazepines, and we should use a multimodal therapy with opioid-sparing and regional techniques.”

Pulmonary considerations for anesthesia include susceptibility to hypocarbia and hypoxemia, and susceptibility to residual anesthetic effects. “Because of physiologic changes, the anesthesia medications aren’t metabolized in the same way,” she said. “Older people may have lower drug requirements and may not recover as quickly from the effects of these drugs. This can lead to respiratory compromise and also can increase the risk of aspiration.” Strategies to prevent pulmonary complications include using regional anesthesia when possible and avoiding the use of intermediate- and long-acting neuromuscular blocking agents. Dr. Rosenthal said that there is insufficient evidence in the current medical literature to recommend a single “best” intraoperative fluid management plan for all older adults. “Part of the reason it’s so difficult is because of the cardiac physiologic changes [with aging],” she explained. “Older people are susceptible to volume overload. On the other hand, they also may have an exaggerated decline in cardiac function if you give them too little fluid and they have insufficient preload. It’s a very fine line and that’s why it’s hard to recommend a single best strategy.”

Be alert to postoperative delirium

Postoperatively, the guideline recommends that care plans include controlling perioperative acute pain; addressing delirium/cognitive issues; preventing functional decline, falls, pressure ulcers, and urinary track infections; maintaining adequate nutrition; and avoiding pulmonary complications. Dr. Rosenthal underscored the importance of using the four-question Short Confusion Assessment Method (Short CAM) to assess for delirium. “For it to be delirium, there has to be evidence of acute change in mental status from baseline; it has to be acute and fluctuating, and characterized by inattention,” she said. “The patient also has to have either disorganized thinking or an altered level of consciousness.”

Many of the precipitating factors of delirium can be prevented by treating pain, watching medications, preventing dehydration and undernutrition, removing catheters and other devices when possible, preventing constipation, and using minimally invasive techniques to reduce the physiologic stress of surgery. “Sometimes symptoms of delirium are a warning sign that something else is going on, such as an infection, hypoxemia, electrolyte imbalance, neurological events, and major organ dysfunction,” she said. The first-line therapy for treating delirium as recommended in the guideline is a multicomponent intervention that focuses on frequent reorientation with voice, calendars, and clocks; eliminating use of restraints; having familiar objects in the room; and ensuring the use of assistive devices. The second-line therapy is antipsychotic medications at the lowest effective dose. “The mantra is start low and go slow,” she said.

Preventing postoperative functional decline

Another postoperative strategy in the guideline involves targeted fall prevention, such as having an assistive device at the bedside if used as an outpatient and prescribing early physical therapy focused on maintaining mobility as the primary event. “Every day an older patient is immobilized it takes at least 3 days to regain the lost function,” Dr. Rosenthal said. “And for older surgical patients, one in four experiences a significant decline in function by hospital discharge and 60% experience some loss of independence.” (The latter statistic comes from a study published online July 13, 2016, in JAMA Surgery: doi:10.1001/jamasurg.2016.1689.) Interventions for preventing functional decline include promotion of family participation in care, early mobilization, early physical/occupational therapy referral, geriatric consultation, comprehensive discharge planning, and nutritional support. She pointed out that an estimated 40% of community-dwelling elders and two-thirds of nursing home residents are either malnourished or “at risk” of malnutrition.

Transition of care

The final category in the guideline, transition of care, recommends an assessment of social support/home health needs, complete medication review, predischarge geriatric assessment, formal written discharge instructions, and communication with the patient’s primary care physician. “Common models of transitional care involve good coordination with the primary care physician,” she said. “There’s good data to show that people who see their primary care physician within 2 weeks of discharge do better in terms of readmission.”

Dr. Rosenthal reported having no financial disclosures.

[email protected]

SAN DIEGO – As the number of surgery patients over the age of 65 continues to burgeon, clinicians have a resource to help them provide optimal perioperative care to this patient population.

At the American College of Surgeons/National Surgical Quality Improvement Program National Conference, Ronnie A. Rosenthal, MD, discussed highlights from “Optimal Perioperative Management of the Geriatric Patient: A Best Practice Guideline from the ACS NSQIP/American Geriatrics Society,” which was published in January 2016.

Work on the guideline began in 2013, when a 28-member multidisciplinary panel began to conduct a structured search of Medline to identify systematic reviews, meta-analyses, practice guidelines, and clinical trials on the topic. The panel included experts from ACS, the ACS Geriatric Surgery Task Force, the American Society of Anesthesiologists, the American Geriatrics Society, and the AGS’ Geriatrics for Specialists Initiative. The 61-page document is divided into four categories: immediate preoperative period, intraoperative management, postoperative care, and care transitions.

Working with patients on goals

As noted in the guideline, a primary goal of the immediate preoperative period is to discuss with the patient his or her goals and expectations. Patient expectations are influenced by their treatment preferences. In fact, researchers have found that older patients are less likely to want a treatment – even if it results in cure – that may result in severe functional or cognitive impairment. For patients with existing advanced directives, organizations representing nurses, anesthesiologists, and surgeons all agree that there must be a “reconsideration” of these directives prior to surgery. A discussion that includes the new risks of the procedure must be conducted to ensure that the approach to potential life-threatening problems is consistent with the patient’s values.

Preoperative management of medications

Another recommendation for the preoperative period is to ensure that older patients have shorter fasts, have appropriate prophylactic antibiotics, continue medications with withdrawal potential, and discontinue medications that are not essential. The latter point is based on the Beers Criteria, a list of medications that are inappropriate or potentially inappropriate to use in older adults (J Am Geriatr Soc. 2015 Nov;63[11]:2227-46). “You want to discontinue as many inappropriate medications as possible, because one of the main side effects of their use is delirium, and you want to avoid that,” said Dr. Rosenthal, professor of surgery at the Yale University, New Haven, Conn., and one of the guideline authors.

©Thinkstockphotos.com

Anesthesia and pain management

Intraoperative management strategies contained in the guideline include establishing an anesthetic approach and a perioperative analgesia pain plan, preventing postoperative nausea and vomiting, assessing patient safety in the OR, preventing predictable complications, and optimizing fluid management. Physiologic effects of anesthesia medications include changes in systemic vascular resistance, cardiac preload, baroreceptor responses, lung mechanics, oxygen diffusion, neurotransmitter function, and end-organ blood flow, among others. “These physiologic changes of aging have significant clinical implications,” Dr. Rosenthal noted. “These are variable among individuals and variable among organ systems, and it’s important that we pay attention to that. Because of this variability, there is insufficient evidence to recommend a single ‘best’ anesthetic plan for all older adults.”

The guideline recommends that each patient have an individualized pain plan that consists of a directed pain history and physical exam and is appropriately titrated for increased sensitivity. “It should include a prophylactic bowel regimen for anybody who’s on an opioid in particular,” she said. “We should avoid inappropriate medications like benzodiazepines, and we should use a multimodal therapy with opioid-sparing and regional techniques.”

Pulmonary considerations for anesthesia include susceptibility to hypocarbia and hypoxemia, and susceptibility to residual anesthetic effects. “Because of physiologic changes, the anesthesia medications aren’t metabolized in the same way,” she said. “Older people may have lower drug requirements and may not recover as quickly from the effects of these drugs. This can lead to respiratory compromise and also can increase the risk of aspiration.” Strategies to prevent pulmonary complications include using regional anesthesia when possible and avoiding the use of intermediate- and long-acting neuromuscular blocking agents. Dr. Rosenthal said that there is insufficient evidence in the current medical literature to recommend a single “best” intraoperative fluid management plan for all older adults. “Part of the reason it’s so difficult is because of the cardiac physiologic changes [with aging],” she explained. “Older people are susceptible to volume overload. On the other hand, they also may have an exaggerated decline in cardiac function if you give them too little fluid and they have insufficient preload. It’s a very fine line and that’s why it’s hard to recommend a single best strategy.”

Be alert to postoperative delirium

Postoperatively, the guideline recommends that care plans include controlling perioperative acute pain; addressing delirium/cognitive issues; preventing functional decline, falls, pressure ulcers, and urinary track infections; maintaining adequate nutrition; and avoiding pulmonary complications. Dr. Rosenthal underscored the importance of using the four-question Short Confusion Assessment Method (Short CAM) to assess for delirium. “For it to be delirium, there has to be evidence of acute change in mental status from baseline; it has to be acute and fluctuating, and characterized by inattention,” she said. “The patient also has to have either disorganized thinking or an altered level of consciousness.”

Many of the precipitating factors of delirium can be prevented by treating pain, watching medications, preventing dehydration and undernutrition, removing catheters and other devices when possible, preventing constipation, and using minimally invasive techniques to reduce the physiologic stress of surgery. “Sometimes symptoms of delirium are a warning sign that something else is going on, such as an infection, hypoxemia, electrolyte imbalance, neurological events, and major organ dysfunction,” she said. The first-line therapy for treating delirium as recommended in the guideline is a multicomponent intervention that focuses on frequent reorientation with voice, calendars, and clocks; eliminating use of restraints; having familiar objects in the room; and ensuring the use of assistive devices. The second-line therapy is antipsychotic medications at the lowest effective dose. “The mantra is start low and go slow,” she said.

Preventing postoperative functional decline

Another postoperative strategy in the guideline involves targeted fall prevention, such as having an assistive device at the bedside if used as an outpatient and prescribing early physical therapy focused on maintaining mobility as the primary event. “Every day an older patient is immobilized it takes at least 3 days to regain the lost function,” Dr. Rosenthal said. “And for older surgical patients, one in four experiences a significant decline in function by hospital discharge and 60% experience some loss of independence.” (The latter statistic comes from a study published online July 13, 2016, in JAMA Surgery: doi:10.1001/jamasurg.2016.1689.) Interventions for preventing functional decline include promotion of family participation in care, early mobilization, early physical/occupational therapy referral, geriatric consultation, comprehensive discharge planning, and nutritional support. She pointed out that an estimated 40% of community-dwelling elders and two-thirds of nursing home residents are either malnourished or “at risk” of malnutrition.

Transition of care

The final category in the guideline, transition of care, recommends an assessment of social support/home health needs, complete medication review, predischarge geriatric assessment, formal written discharge instructions, and communication with the patient’s primary care physician. “Common models of transitional care involve good coordination with the primary care physician,” she said. “There’s good data to show that people who see their primary care physician within 2 weeks of discharge do better in terms of readmission.”

Dr. Rosenthal reported having no financial disclosures.

[email protected]

Risk-assessment tools can give surgeons a clinical framework to help inform decisions about palliative care surgery in patients with advanced malignancies, but cannot replace nuanced clinical judgment that incorporates patients’ priorities, according to results of a meta-analysis.

Ian W. Folkert, MD, and Robert E. Roses, MD, of the department of surgery at the Hospital of the University of Pennsylvania, Philadelphia, reviewed the available research on the indications for palliative surgery for patients with advanced disease and risk-assessment tools for patient selection. Emergent and palliative surgery in such situations require a careful consideration of many clinical factors such as overall prognosis and risk of a surgical approach, compared with nonsurgical interventions (J Surg Oncol. 2016;114:[3]311-15). But the investigators concluded that while an evidence-based approach to patient selection for palliative cancer surgery can offer some guidance on the potential for achieving clinical goals, ultimately the decision to proceed must prioritize patient values and orientation to treatment.

Tumor bleeding

Tumor-related complications often initiate the question of palliative surgical and nonsurgical interventions.

Studies of acute hemorrhage from malignancies indicate that bleeding originating from a tumor is rarely massive and usually can be managed endoscopically (Clin Endosc. 2015 Mar;48[2]:121-7; Aliment Pharmacol Ther. 2013;38:144-50; Mayo Clin Proc. 1994;69[8]:736-40). Transcatheter arterial embolization also is used successfully to manage tumor bleeding (J Vasc Interv Radiol. 2015 Sep;26[9]:1297-304; Indian J Cancer. 2014 Feb; 51[6]56-9). The investigators stated, “Although tumor rebleeding may be frequent, repeat endoscopy is often effective and is self-recommending given the high risk of major morbidity after a palliative foregut resection ... [and] all efforts should be made to avoid emergency gastrectomy or esophagectomy.”

Obstructing tumors

Patients with acute colonic obstruction because of colon cancer typically have been treated with a proximal diverting colostomy, but palliative self-expanding metallic stent placement (SEMS) has emerged as an option. Recent studies have shown both short- and long-term clinical success of SEMS, but rates of major morbidity and mortality for emergent surgery and SEMS were similar, as were rates of overall survival (Surg Endosc. 2015;29[6];1580-5; World J Gastroenterol. 2013 Sep 7;19[33]:5565-74). SEMS-related mortality was primarily because of perforation (Endoscopy. 2008 Mar;40[3]:184-91). Stenting for esophageal and gastroesophageal (GE) function obstruction is also emerging as a nonsurgical option. The investigators noted, “There is a very limited role for palliative surgery for esophageal and GE junction tumors.” Gastric outlet obstruction, proximal duodenal obstruction, and biliary tract obstruction are treated palliatively with stents, but “gastrojejunostomy and other bypass operations may provide effective palliation in carefully selected patients.”

Tumor perforation

Few nonsurgical treatment options are available for tumor perforation. Palliative surgical intervention often is undertaken in the context of neutropenia and abdominal pain, the investigators said. These patients are at high risk for morbidity and mortality. One study reviewed found that “prolonged neutropenia and severe sepsis were associated with poor outcomes in all patients, while surgical management was associated with improved survival (Ann Surg. 2008;248[1];104-9), but nonoperative management and comfort care were deemed appropriate for those patients with advanced disease and for those in whom surgery is high risk.

Patient selection for palliative surgery

The studies examined suggest that patient selection for palliative surgical intervention requires the weighing of clinical variables of frailty, morbidity, and mortality. The investigators reviewed a variety of risk-assessment tools developed to help surgeons with that decision (J Am Coll Surg. 2003;197[1];16-21; J Palliat Med. 2014;17:37-42; Ann Surg. 2011;254[2]:333-8). Among the factors considered are the amplified risks of mortality in these patients, the high cost of emergent operations, and most importantly, the chances of extending survival. The complexity of palliative and emergent surgical indications means that risk-assessment studies are “frequently too reductive to provide meaningful guidance” to the surgeon.

Dr. Folkert and Dr. Roses concluded that risk-assessment tools underscore the poor outcomes associated with operations in this setting, and, to some extent, guide decision making, but “they do not supplant clinical judgment, nor do they account for patient values and orientation toward treatment. It remains impossible to place a uniform value on length and quality of life, and patients’ values are paramount in informing treatment decisions.”

The authors had no conflicts to disclose.

Risk-assessment tools can give surgeons a clinical framework to help inform decisions about palliative care surgery in patients with advanced malignancies, but cannot replace nuanced clinical judgment that incorporates patients’ priorities, according to results of a meta-analysis.

Ian W. Folkert, MD, and Robert E. Roses, MD, of the department of surgery at the Hospital of the University of Pennsylvania, Philadelphia, reviewed the available research on the indications for palliative surgery for patients with advanced disease and risk-assessment tools for patient selection. Emergent and palliative surgery in such situations require a careful consideration of many clinical factors such as overall prognosis and risk of a surgical approach, compared with nonsurgical interventions (J Surg Oncol. 2016;114:[3]311-15). But the investigators concluded that while an evidence-based approach to patient selection for palliative cancer surgery can offer some guidance on the potential for achieving clinical goals, ultimately the decision to proceed must prioritize patient values and orientation to treatment.

Tumor bleeding

Tumor-related complications often initiate the question of palliative surgical and nonsurgical interventions.

Studies of acute hemorrhage from malignancies indicate that bleeding originating from a tumor is rarely massive and usually can be managed endoscopically (Clin Endosc. 2015 Mar;48[2]:121-7; Aliment Pharmacol Ther. 2013;38:144-50; Mayo Clin Proc. 1994;69[8]:736-40). Transcatheter arterial embolization also is used successfully to manage tumor bleeding (J Vasc Interv Radiol. 2015 Sep;26[9]:1297-304; Indian J Cancer. 2014 Feb; 51[6]56-9). The investigators stated, “Although tumor rebleeding may be frequent, repeat endoscopy is often effective and is self-recommending given the high risk of major morbidity after a palliative foregut resection ... [and] all efforts should be made to avoid emergency gastrectomy or esophagectomy.”

Obstructing tumors

Patients with acute colonic obstruction because of colon cancer typically have been treated with a proximal diverting colostomy, but palliative self-expanding metallic stent placement (SEMS) has emerged as an option. Recent studies have shown both short- and long-term clinical success of SEMS, but rates of major morbidity and mortality for emergent surgery and SEMS were similar, as were rates of overall survival (Surg Endosc. 2015;29[6];1580-5; World J Gastroenterol. 2013 Sep 7;19[33]:5565-74). SEMS-related mortality was primarily because of perforation (Endoscopy. 2008 Mar;40[3]:184-91). Stenting for esophageal and gastroesophageal (GE) function obstruction is also emerging as a nonsurgical option. The investigators noted, “There is a very limited role for palliative surgery for esophageal and GE junction tumors.” Gastric outlet obstruction, proximal duodenal obstruction, and biliary tract obstruction are treated palliatively with stents, but “gastrojejunostomy and other bypass operations may provide effective palliation in carefully selected patients.”

Tumor perforation

Few nonsurgical treatment options are available for tumor perforation. Palliative surgical intervention often is undertaken in the context of neutropenia and abdominal pain, the investigators said. These patients are at high risk for morbidity and mortality. One study reviewed found that “prolonged neutropenia and severe sepsis were associated with poor outcomes in all patients, while surgical management was associated with improved survival (Ann Surg. 2008;248[1];104-9), but nonoperative management and comfort care were deemed appropriate for those patients with advanced disease and for those in whom surgery is high risk.

Patient selection for palliative surgery

The studies examined suggest that patient selection for palliative surgical intervention requires the weighing of clinical variables of frailty, morbidity, and mortality. The investigators reviewed a variety of risk-assessment tools developed to help surgeons with that decision (J Am Coll Surg. 2003;197[1];16-21; J Palliat Med. 2014;17:37-42; Ann Surg. 2011;254[2]:333-8). Among the factors considered are the amplified risks of mortality in these patients, the high cost of emergent operations, and most importantly, the chances of extending survival. The complexity of palliative and emergent surgical indications means that risk-assessment studies are “frequently too reductive to provide meaningful guidance” to the surgeon.

Dr. Folkert and Dr. Roses concluded that risk-assessment tools underscore the poor outcomes associated with operations in this setting, and, to some extent, guide decision making, but “they do not supplant clinical judgment, nor do they account for patient values and orientation toward treatment. It remains impossible to place a uniform value on length and quality of life, and patients’ values are paramount in informing treatment decisions.”

The authors had no conflicts to disclose.

Risk-assessment tools can give surgeons a clinical framework to help inform decisions about palliative care surgery in patients with advanced malignancies, but cannot replace nuanced clinical judgment that incorporates patients’ priorities, according to results of a meta-analysis.

Ian W. Folkert, MD, and Robert E. Roses, MD, of the department of surgery at the Hospital of the University of Pennsylvania, Philadelphia, reviewed the available research on the indications for palliative surgery for patients with advanced disease and risk-assessment tools for patient selection. Emergent and palliative surgery in such situations require a careful consideration of many clinical factors such as overall prognosis and risk of a surgical approach, compared with nonsurgical interventions (J Surg Oncol. 2016;114:[3]311-15). But the investigators concluded that while an evidence-based approach to patient selection for palliative cancer surgery can offer some guidance on the potential for achieving clinical goals, ultimately the decision to proceed must prioritize patient values and orientation to treatment.

Tumor bleeding

Tumor-related complications often initiate the question of palliative surgical and nonsurgical interventions.

Studies of acute hemorrhage from malignancies indicate that bleeding originating from a tumor is rarely massive and usually can be managed endoscopically (Clin Endosc. 2015 Mar;48[2]:121-7; Aliment Pharmacol Ther. 2013;38:144-50; Mayo Clin Proc. 1994;69[8]:736-40). Transcatheter arterial embolization also is used successfully to manage tumor bleeding (J Vasc Interv Radiol. 2015 Sep;26[9]:1297-304; Indian J Cancer. 2014 Feb; 51[6]56-9). The investigators stated, “Although tumor rebleeding may be frequent, repeat endoscopy is often effective and is self-recommending given the high risk of major morbidity after a palliative foregut resection ... [and] all efforts should be made to avoid emergency gastrectomy or esophagectomy.”

Obstructing tumors

Patients with acute colonic obstruction because of colon cancer typically have been treated with a proximal diverting colostomy, but palliative self-expanding metallic stent placement (SEMS) has emerged as an option. Recent studies have shown both short- and long-term clinical success of SEMS, but rates of major morbidity and mortality for emergent surgery and SEMS were similar, as were rates of overall survival (Surg Endosc. 2015;29[6];1580-5; World J Gastroenterol. 2013 Sep 7;19[33]:5565-74). SEMS-related mortality was primarily because of perforation (Endoscopy. 2008 Mar;40[3]:184-91). Stenting for esophageal and gastroesophageal (GE) function obstruction is also emerging as a nonsurgical option. The investigators noted, “There is a very limited role for palliative surgery for esophageal and GE junction tumors.” Gastric outlet obstruction, proximal duodenal obstruction, and biliary tract obstruction are treated palliatively with stents, but “gastrojejunostomy and other bypass operations may provide effective palliation in carefully selected patients.”

Tumor perforation

Few nonsurgical treatment options are available for tumor perforation. Palliative surgical intervention often is undertaken in the context of neutropenia and abdominal pain, the investigators said. These patients are at high risk for morbidity and mortality. One study reviewed found that “prolonged neutropenia and severe sepsis were associated with poor outcomes in all patients, while surgical management was associated with improved survival (Ann Surg. 2008;248[1];104-9), but nonoperative management and comfort care were deemed appropriate for those patients with advanced disease and for those in whom surgery is high risk.

Patient selection for palliative surgery

The studies examined suggest that patient selection for palliative surgical intervention requires the weighing of clinical variables of frailty, morbidity, and mortality. The investigators reviewed a variety of risk-assessment tools developed to help surgeons with that decision (J Am Coll Surg. 2003;197[1];16-21; J Palliat Med. 2014;17:37-42; Ann Surg. 2011;254[2]:333-8). Among the factors considered are the amplified risks of mortality in these patients, the high cost of emergent operations, and most importantly, the chances of extending survival. The complexity of palliative and emergent surgical indications means that risk-assessment studies are “frequently too reductive to provide meaningful guidance” to the surgeon.

Dr. Folkert and Dr. Roses concluded that risk-assessment tools underscore the poor outcomes associated with operations in this setting, and, to some extent, guide decision making, but “they do not supplant clinical judgment, nor do they account for patient values and orientation toward treatment. It remains impossible to place a uniform value on length and quality of life, and patients’ values are paramount in informing treatment decisions.”

The authors had no conflicts to disclose.

The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.

Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).

©Mark Kostich/Thinkstock

“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.

The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.

However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).

“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).

The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.

It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.

The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.

Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.

Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.

Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).

Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.

“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.

The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.

Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).

©Mark Kostich/Thinkstock

“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.

The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.

However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).

“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).

The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.

It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.

The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.

Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.

Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.

Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).

Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.

“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.

The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.

Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).

©Mark Kostich/Thinkstock

“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.

The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.

However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).

“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).

The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.

It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.

The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.

Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.

Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.

Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).

Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.

“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.

The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

MUNICH – When it comes to predicting mortality in diabetes patients, the foot may trump the heart.

Over a 5-year period, patients who had the most severe foot pathology were almost four times more likely to die than those who had a constellation of cardiovascular risk factors. The association with foot pathology stayed strong and, in a multivariate analysis, was the only factor that remained significantly associated with death in the cohort, Dragan Tesic, MD, said at the annual meeting of the European Association for the Study of Diabetes.

©donskarpo/thinkstockphotos.com

“On average, our patients with severe foot pathology had a 5-year shortening of their lifespan,” said Dr. Tesic of the University of Novi Sad, Serbia. This finding was even more pronounced in younger patients: Those aged 55 years and younger with severe foot pathology died a median of 14 years earlier than their normal expected lifespan would have ended.

Dr. Tesic and his colleagues conducted a 5-year mortality analysis of 244 patients with diabetes, 12% of whom had type 1 disease. The analysis included cardiovascular risk factors (hypertension, triglycerides, cholesterol levels, fibrinogen, proteinuria, and smoking); diabetes duration; coronary artery and cerebrovascular disease; and peripheral artery disease.

Foot pathology was determined according the recently published clinical guidelines by the International Working Group on the Diabetic Foot (IWGDF) (Diab Met Res Rev. 2016. doi: 10.1002/dmrr.2694).

The document parses the diabetic foot into four severity categories:

• 0: No peripheral neuropathy.

• 1: Peripheral neuropathy.

• 2: Peripheral neuropathy with peripheral artery disease and/or a foot deformity.

• 3: Peripheral neuropathy and a history of a foot ulcer or a lower-extremity amputation.

At baseline, patients were a median of 68 years old, though they ranged in age from 36 to 83 years. The mean duration of diabetes was 17 years, and the mean HbA_1c was 8.9%. About half had retinopathy; no one was on hemodialysis.

By 5 years, 53 patients (22%) had died. Their median age was 70 years – 5 years short of the Serbian national life expectancy. However, deaths were evenly distributed among the age groups, Dr. Tesic said: 30% of deceased patients were aged 40-64, 41% aged 65-74, and 28% aged 74 and older.

The causes of death were sudden cardiac death (38%), acute coronary syndrome (32%), stroke (11%), cancer (13%), and sepsis (6%).

There were no significant between-group differences in the type of diabetes; any lipid parameter; diabetic retinopathy; proteinuria; or cardiovascular or cerebrovascular disease. However, patients who died had significantly more severe foot pathology, with 71% scoring either a 2 or 3 on the IWGDF scale compared with 36% of those who were still alive. This level of foot pathology was seen in every age group of the deceased patients: 75% of those in the youngest, 54% of those in the middle group, and 73% of those in the oldest group.

Those who died had developed their foot lesions earlier (66 years vs. 69 years). They had poorer ankle reflexes, and worse results on the Neuropad, a visual indicator test for human diabetic neuropathy. Those who died were older (70 years vs. 66 years), had a longer diabetes duration (20 years vs. 17 years), and more hypertension (79% vs. 61%).

But in a multivariate analysis, only the IWGDF score remained a significant predictor of mortality (odds ratio, 3.78). All of the cardiovascular risk factors, as well as age, diabetes duration, and glucose measures, had no effect on survivalk in that analysis.

The study underscores the importance of preventing and treating diabetic neuropathy and foot complications, Dr. Tesic stressed.

“I like to say that I see an opportunity in every difficulty. The examination of the diabetic foot may be time-consuming, but without that we are not delivering adequate or appropriate care to our patients.”

He had no financial disclosures.

[email protected]

MUNICH – When it comes to predicting mortality in diabetes patients, the foot may trump the heart.

Over a 5-year period, patients who had the most severe foot pathology were almost four times more likely to die than those who had a constellation of cardiovascular risk factors. The association with foot pathology stayed strong and, in a multivariate analysis, was the only factor that remained significantly associated with death in the cohort, Dragan Tesic, MD, said at the annual meeting of the European Association for the Study of Diabetes.

©donskarpo/thinkstockphotos.com

“On average, our patients with severe foot pathology had a 5-year shortening of their lifespan,” said Dr. Tesic of the University of Novi Sad, Serbia. This finding was even more pronounced in younger patients: Those aged 55 years and younger with severe foot pathology died a median of 14 years earlier than their normal expected lifespan would have ended.

Dr. Tesic and his colleagues conducted a 5-year mortality analysis of 244 patients with diabetes, 12% of whom had type 1 disease. The analysis included cardiovascular risk factors (hypertension, triglycerides, cholesterol levels, fibrinogen, proteinuria, and smoking); diabetes duration; coronary artery and cerebrovascular disease; and peripheral artery disease.

Foot pathology was determined according the recently published clinical guidelines by the International Working Group on the Diabetic Foot (IWGDF) (Diab Met Res Rev. 2016. doi: 10.1002/dmrr.2694).

The document parses the diabetic foot into four severity categories:

• 0: No peripheral neuropathy.

• 1: Peripheral neuropathy.

• 2: Peripheral neuropathy with peripheral artery disease and/or a foot deformity.

• 3: Peripheral neuropathy and a history of a foot ulcer or a lower-extremity amputation.

At baseline, patients were a median of 68 years old, though they ranged in age from 36 to 83 years. The mean duration of diabetes was 17 years, and the mean HbA_1c was 8.9%. About half had retinopathy; no one was on hemodialysis.

By 5 years, 53 patients (22%) had died. Their median age was 70 years – 5 years short of the Serbian national life expectancy. However, deaths were evenly distributed among the age groups, Dr. Tesic said: 30% of deceased patients were aged 40-64, 41% aged 65-74, and 28% aged 74 and older.

The causes of death were sudden cardiac death (38%), acute coronary syndrome (32%), stroke (11%), cancer (13%), and sepsis (6%).

There were no significant between-group differences in the type of diabetes; any lipid parameter; diabetic retinopathy; proteinuria; or cardiovascular or cerebrovascular disease. However, patients who died had significantly more severe foot pathology, with 71% scoring either a 2 or 3 on the IWGDF scale compared with 36% of those who were still alive. This level of foot pathology was seen in every age group of the deceased patients: 75% of those in the youngest, 54% of those in the middle group, and 73% of those in the oldest group.

Those who died had developed their foot lesions earlier (66 years vs. 69 years). They had poorer ankle reflexes, and worse results on the Neuropad, a visual indicator test for human diabetic neuropathy. Those who died were older (70 years vs. 66 years), had a longer diabetes duration (20 years vs. 17 years), and more hypertension (79% vs. 61%).

But in a multivariate analysis, only the IWGDF score remained a significant predictor of mortality (odds ratio, 3.78). All of the cardiovascular risk factors, as well as age, diabetes duration, and glucose measures, had no effect on survivalk in that analysis.

The study underscores the importance of preventing and treating diabetic neuropathy and foot complications, Dr. Tesic stressed.

“I like to say that I see an opportunity in every difficulty. The examination of the diabetic foot may be time-consuming, but without that we are not delivering adequate or appropriate care to our patients.”

He had no financial disclosures.

[email protected]

MUNICH – When it comes to predicting mortality in diabetes patients, the foot may trump the heart.

Over a 5-year period, patients who had the most severe foot pathology were almost four times more likely to die than those who had a constellation of cardiovascular risk factors. The association with foot pathology stayed strong and, in a multivariate analysis, was the only factor that remained significantly associated with death in the cohort, Dragan Tesic, MD, said at the annual meeting of the European Association for the Study of Diabetes.

©donskarpo/thinkstockphotos.com

“On average, our patients with severe foot pathology had a 5-year shortening of their lifespan,” said Dr. Tesic of the University of Novi Sad, Serbia. This finding was even more pronounced in younger patients: Those aged 55 years and younger with severe foot pathology died a median of 14 years earlier than their normal expected lifespan would have ended.

Dr. Tesic and his colleagues conducted a 5-year mortality analysis of 244 patients with diabetes, 12% of whom had type 1 disease. The analysis included cardiovascular risk factors (hypertension, triglycerides, cholesterol levels, fibrinogen, proteinuria, and smoking); diabetes duration; coronary artery and cerebrovascular disease; and peripheral artery disease.

Foot pathology was determined according the recently published clinical guidelines by the International Working Group on the Diabetic Foot (IWGDF) (Diab Met Res Rev. 2016. doi: 10.1002/dmrr.2694).

The document parses the diabetic foot into four severity categories:

• 0: No peripheral neuropathy.

• 1: Peripheral neuropathy.

• 2: Peripheral neuropathy with peripheral artery disease and/or a foot deformity.

• 3: Peripheral neuropathy and a history of a foot ulcer or a lower-extremity amputation.

At baseline, patients were a median of 68 years old, though they ranged in age from 36 to 83 years. The mean duration of diabetes was 17 years, and the mean HbA_1c was 8.9%. About half had retinopathy; no one was on hemodialysis.

By 5 years, 53 patients (22%) had died. Their median age was 70 years – 5 years short of the Serbian national life expectancy. However, deaths were evenly distributed among the age groups, Dr. Tesic said: 30% of deceased patients were aged 40-64, 41% aged 65-74, and 28% aged 74 and older.

The causes of death were sudden cardiac death (38%), acute coronary syndrome (32%), stroke (11%), cancer (13%), and sepsis (6%).

There were no significant between-group differences in the type of diabetes; any lipid parameter; diabetic retinopathy; proteinuria; or cardiovascular or cerebrovascular disease. However, patients who died had significantly more severe foot pathology, with 71% scoring either a 2 or 3 on the IWGDF scale compared with 36% of those who were still alive. This level of foot pathology was seen in every age group of the deceased patients: 75% of those in the youngest, 54% of those in the middle group, and 73% of those in the oldest group.

Those who died had developed their foot lesions earlier (66 years vs. 69 years). They had poorer ankle reflexes, and worse results on the Neuropad, a visual indicator test for human diabetic neuropathy. Those who died were older (70 years vs. 66 years), had a longer diabetes duration (20 years vs. 17 years), and more hypertension (79% vs. 61%).

But in a multivariate analysis, only the IWGDF score remained a significant predictor of mortality (odds ratio, 3.78). All of the cardiovascular risk factors, as well as age, diabetes duration, and glucose measures, had no effect on survivalk in that analysis.

The study underscores the importance of preventing and treating diabetic neuropathy and foot complications, Dr. Tesic stressed.

“I like to say that I see an opportunity in every difficulty. The examination of the diabetic foot may be time-consuming, but without that we are not delivering adequate or appropriate care to our patients.”

He had no financial disclosures.

[email protected]

A pathogen infects some people and not others. Some people spread the infection, others don’t. Is it possible to predict who’s likely to be contagious—and perhaps head off an epidemic or pandemic? The Defense Advanced Research Projects Agency’s new Prometheus program may help.

Related: Legionnaires Disease: An Ever-Growing Risk

Focusing on acute respiratory infections, Prometheus researchers will aim to pin down the biological responses that occur in infection, especially the early molecular signals that are triggered soon after exposure. The goal is to develop a prognostic assay based on information from, for example, the amount of virus detected during viral shedding, the genes inside immune-system cells, messenger RNA, immune-system proteins, and other biomarkers.

Current efforts at outbreak containment rely heavily on reported cases, generated after the fact—someone has already become sick and exposed others to the disease. That doesn’t even include people with mild symptoms who don’t go to the doctor but can still spread the disease. A “minimal set of early host biomarkers” could indicate, less than 24 hours after exposure to a pathogen, who will become contagious, opening a window to allow early treatment or mitigation.

Related: Identification and Management of Middle East Respiratory Syndrome

The announcement by DARPA about Prometheus cites a recent review that shows understanding presymptomatic infection is required to achieve accurate forecasting; using only diagnostics is inadequate. “Our goal with Prometheus is to develop techniques that could alert people that they are likely to become contagious,” said Army Col. Matt Hepburn, Prometheus program manager, “so they can proactively take steps to keep the disease from spreading.”

A pathogen infects some people and not others. Some people spread the infection, others don’t. Is it possible to predict who’s likely to be contagious—and perhaps head off an epidemic or pandemic? The Defense Advanced Research Projects Agency’s new Prometheus program may help.

Related: Legionnaires Disease: An Ever-Growing Risk

Focusing on acute respiratory infections, Prometheus researchers will aim to pin down the biological responses that occur in infection, especially the early molecular signals that are triggered soon after exposure. The goal is to develop a prognostic assay based on information from, for example, the amount of virus detected during viral shedding, the genes inside immune-system cells, messenger RNA, immune-system proteins, and other biomarkers.

Current efforts at outbreak containment rely heavily on reported cases, generated after the fact—someone has already become sick and exposed others to the disease. That doesn’t even include people with mild symptoms who don’t go to the doctor but can still spread the disease. A “minimal set of early host biomarkers” could indicate, less than 24 hours after exposure to a pathogen, who will become contagious, opening a window to allow early treatment or mitigation.

Related: Identification and Management of Middle East Respiratory Syndrome

The announcement by DARPA about Prometheus cites a recent review that shows understanding presymptomatic infection is required to achieve accurate forecasting; using only diagnostics is inadequate. “Our goal with Prometheus is to develop techniques that could alert people that they are likely to become contagious,” said Army Col. Matt Hepburn, Prometheus program manager, “so they can proactively take steps to keep the disease from spreading.”

A pathogen infects some people and not others. Some people spread the infection, others don’t. Is it possible to predict who’s likely to be contagious—and perhaps head off an epidemic or pandemic? The Defense Advanced Research Projects Agency’s new Prometheus program may help.

Related: Legionnaires Disease: An Ever-Growing Risk

Focusing on acute respiratory infections, Prometheus researchers will aim to pin down the biological responses that occur in infection, especially the early molecular signals that are triggered soon after exposure. The goal is to develop a prognostic assay based on information from, for example, the amount of virus detected during viral shedding, the genes inside immune-system cells, messenger RNA, immune-system proteins, and other biomarkers.

Current efforts at outbreak containment rely heavily on reported cases, generated after the fact—someone has already become sick and exposed others to the disease. That doesn’t even include people with mild symptoms who don’t go to the doctor but can still spread the disease. A “minimal set of early host biomarkers” could indicate, less than 24 hours after exposure to a pathogen, who will become contagious, opening a window to allow early treatment or mitigation.

Related: Identification and Management of Middle East Respiratory Syndrome

The announcement by DARPA about Prometheus cites a recent review that shows understanding presymptomatic infection is required to achieve accurate forecasting; using only diagnostics is inadequate. “Our goal with Prometheus is to develop techniques that could alert people that they are likely to become contagious,” said Army Col. Matt Hepburn, Prometheus program manager, “so they can proactively take steps to keep the disease from spreading.”

Prescription medications

Photo courtesy of CDC

Results of a retrospective study suggest statins may decrease the risk of death in patients with multiple myeloma (MM).

Researchers analyzed data from nearly 5000 patients with MM and found that patients who took statins had a significant reduction in all-cause mortality and MM-specific mortality when compared to patients who did not take these drugs.

Kristen Marie Sanfilippo, MD, of Washington University School of Medicine in St Louis, Missouri, and her colleagues reported these findings in the Journal of Clinical Oncology.

The researchers analyzed data from the Veterans Administration Central Cancer Registry and identified 4957 patients who were diagnosed with MM between 1999 and 2013.

Of these patients, 2294 were classified as statin users. The researchers defined statin use as the presence of any prescription for a statin within 3 months before MM diagnosis or any time thereafter.

The data showed that statin users had a longer median survival than non-users—39.5 months and 27 months, respectively.

When the researchers adjusted for potential confounders, they found that statin users had a 21% reduction in the risk of all-cause mortality (adjusted hazard ratio [aHR]=0.79, P<0.001) and a 24% reduction in the risk of MM-specific mortality (aHR=0.76, P<0.001).

In addition, statin users had a 31% reduction in the risk of developing a skeletal-related event (aHR=0.69, P<0.001).

In a 12-month landmark analysis, statin use was associated with a significant reduction in the risk of all-cause mortality (aHR=0.86, P=0.001) and MM-specific mortality (aHR=0.83, P=0.01).

The reduction in all-cause mortality was 12% (P=0.004) for patients taking statins for at least 3 months, 16% (P<0.001) for patients taking statins for at least 6 months, and 18% (P=0.003) for patients taking statins for at least 9 months.

Patients with less than 365 daily defined doses (DDDs) of statins had a 20% reduction in the risk of all-cause mortality (aHR=0.80, P<0.001). And patients with ≥ 365 DDDs had a 22% reduction in the risk of all-cause mortality (aHR=0.78, P<0.001).

The reductions in MM-specific mortality according to DDDs were 22% (aHR=0.78, P=0.001) and 28% (aHR=0.72, P<0.001), respectively.

The researchers further adjusted for baseline differences between statin users and non-users with propensity-score matching. And statin use was still associated with a reduction in all-cause mortality (aHR=0.78, P<0.001) and MM-specific mortality (aHR=0.79, P=0.007).

The researchers said these results suggest a potential role for statin therapy in patients with MM, although the findings should be corroborated in prospective studies.

Prescription medications

Photo courtesy of CDC

Results of a retrospective study suggest statins may decrease the risk of death in patients with multiple myeloma (MM).

Researchers analyzed data from nearly 5000 patients with MM and found that patients who took statins had a significant reduction in all-cause mortality and MM-specific mortality when compared to patients who did not take these drugs.

Kristen Marie Sanfilippo, MD, of Washington University School of Medicine in St Louis, Missouri, and her colleagues reported these findings in the Journal of Clinical Oncology.

The researchers analyzed data from the Veterans Administration Central Cancer Registry and identified 4957 patients who were diagnosed with MM between 1999 and 2013.

Of these patients, 2294 were classified as statin users. The researchers defined statin use as the presence of any prescription for a statin within 3 months before MM diagnosis or any time thereafter.

The data showed that statin users had a longer median survival than non-users—39.5 months and 27 months, respectively.

When the researchers adjusted for potential confounders, they found that statin users had a 21% reduction in the risk of all-cause mortality (adjusted hazard ratio [aHR]=0.79, P<0.001) and a 24% reduction in the risk of MM-specific mortality (aHR=0.76, P<0.001).

In addition, statin users had a 31% reduction in the risk of developing a skeletal-related event (aHR=0.69, P<0.001).

In a 12-month landmark analysis, statin use was associated with a significant reduction in the risk of all-cause mortality (aHR=0.86, P=0.001) and MM-specific mortality (aHR=0.83, P=0.01).

The reduction in all-cause mortality was 12% (P=0.004) for patients taking statins for at least 3 months, 16% (P<0.001) for patients taking statins for at least 6 months, and 18% (P=0.003) for patients taking statins for at least 9 months.

Patients with less than 365 daily defined doses (DDDs) of statins had a 20% reduction in the risk of all-cause mortality (aHR=0.80, P<0.001). And patients with ≥ 365 DDDs had a 22% reduction in the risk of all-cause mortality (aHR=0.78, P<0.001).

The reductions in MM-specific mortality according to DDDs were 22% (aHR=0.78, P=0.001) and 28% (aHR=0.72, P<0.001), respectively.

The researchers further adjusted for baseline differences between statin users and non-users with propensity-score matching. And statin use was still associated with a reduction in all-cause mortality (aHR=0.78, P<0.001) and MM-specific mortality (aHR=0.79, P=0.007).

The researchers said these results suggest a potential role for statin therapy in patients with MM, although the findings should be corroborated in prospective studies.

Prescription medications

Photo courtesy of CDC

Results of a retrospective study suggest statins may decrease the risk of death in patients with multiple myeloma (MM).

Researchers analyzed data from nearly 5000 patients with MM and found that patients who took statins had a significant reduction in all-cause mortality and MM-specific mortality when compared to patients who did not take these drugs.

Kristen Marie Sanfilippo, MD, of Washington University School of Medicine in St Louis, Missouri, and her colleagues reported these findings in the Journal of Clinical Oncology.

The researchers analyzed data from the Veterans Administration Central Cancer Registry and identified 4957 patients who were diagnosed with MM between 1999 and 2013.

Of these patients, 2294 were classified as statin users. The researchers defined statin use as the presence of any prescription for a statin within 3 months before MM diagnosis or any time thereafter.

The data showed that statin users had a longer median survival than non-users—39.5 months and 27 months, respectively.

When the researchers adjusted for potential confounders, they found that statin users had a 21% reduction in the risk of all-cause mortality (adjusted hazard ratio [aHR]=0.79, P<0.001) and a 24% reduction in the risk of MM-specific mortality (aHR=0.76, P<0.001).

In addition, statin users had a 31% reduction in the risk of developing a skeletal-related event (aHR=0.69, P<0.001).

In a 12-month landmark analysis, statin use was associated with a significant reduction in the risk of all-cause mortality (aHR=0.86, P=0.001) and MM-specific mortality (aHR=0.83, P=0.01).

The reduction in all-cause mortality was 12% (P=0.004) for patients taking statins for at least 3 months, 16% (P<0.001) for patients taking statins for at least 6 months, and 18% (P=0.003) for patients taking statins for at least 9 months.

Patients with less than 365 daily defined doses (DDDs) of statins had a 20% reduction in the risk of all-cause mortality (aHR=0.80, P<0.001). And patients with ≥ 365 DDDs had a 22% reduction in the risk of all-cause mortality (aHR=0.78, P<0.001).

The reductions in MM-specific mortality according to DDDs were 22% (aHR=0.78, P=0.001) and 28% (aHR=0.72, P<0.001), respectively.

The researchers further adjusted for baseline differences between statin users and non-users with propensity-score matching. And statin use was still associated with a reduction in all-cause mortality (aHR=0.78, P<0.001) and MM-specific mortality (aHR=0.79, P=0.007).

The researchers said these results suggest a potential role for statin therapy in patients with MM, although the findings should be corroborated in prospective studies.

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

Doctor and patient in hospital

Photo courtesy of CDC

New research suggests that many patients who die of cancer do not receive strong opioid medications in their last year of life, despite the fact that these drugs are the recommended treatment for cancer-related pain.

Researchers used UK Cancer Registry Data to study more than 6000 cancer patients who died over a 7-year period.

Less than half of these patients received prescriptions for strong opioid medications in their last year of life.

Among those patients who did receive such prescriptions, many received them late.

Lucy Ziegler, PhD, of the University of Leeds in the UK, and her colleagues conducted this study and reported the results in PAIN.

The study included 6080 cancer patients who died between 2005 and 2012.

About 76% (n=4610) of these patients had received one or more prescriptions for analgesics, including 48% (n=2919) who received a strong opioid and 28% (n=1691) who received a non-opioid or weak opioid. The remaining 24% (n=1470) did not receive any prescription analgesic.

The chance of receiving strong opioids was not affected by patients’ age or sex.

However, patients who died in a hospital were 60% less likely to have a prescription for strong opioids during the last year of life, when compared with those who died in hospice.

And patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than patients who did not receive chemotherapy.

Timing of therapy

Among the patients who did receive strong opioids, the median time between receiving the medication and death was 9 weeks. By 6 weeks before death, just 30% of patients had been prescribed a strong opioid.

The researchers noted that these figures don’t match up with previous studies reporting that severe pain can occur “much earlier in the cancer trajectory.”

Older patients were more likely to receive their strong opioid prescription late (defined as later than 9 weeks before death). After other factors were taken into account, patients age 60 or older were about 2 to 4 times more likely to be in the late-prescribing group, compared with those age 50 or younger.

Compared to patients who died in hospice, patients who died in a hospital were 40% more likely to receive a late prescription for a strong opioid. Patients who died in their own home were 2.6 times more likely to receive a late prescription, and patients who died in a care home were 2.8 times more likely to receive a late prescription.

Patients who had surgery were 40% more likely to receive a late prescription than patients who did not undergo surgery.

But patients who received chemotherapy and/or radiotherapy were 30% more likely to have received an early prescription for a strong opioid than patients who did not receive chemo/radiotherapy.

Dr Ziegler and her colleagues noted that this study had its limitations; in particular, the lack of data on pain severity.

Still, the researchers believe their results support the hypothesis of potential under-treatment of cancer pain and suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.

Doctor and patient in hospital

Photo courtesy of CDC

New research suggests that many patients who die of cancer do not receive strong opioid medications in their last year of life, despite the fact that these drugs are the recommended treatment for cancer-related pain.

Researchers used UK Cancer Registry Data to study more than 6000 cancer patients who died over a 7-year period.

Less than half of these patients received prescriptions for strong opioid medications in their last year of life.

Among those patients who did receive such prescriptions, many received them late.

Lucy Ziegler, PhD, of the University of Leeds in the UK, and her colleagues conducted this study and reported the results in PAIN.

The study included 6080 cancer patients who died between 2005 and 2012.

About 76% (n=4610) of these patients had received one or more prescriptions for analgesics, including 48% (n=2919) who received a strong opioid and 28% (n=1691) who received a non-opioid or weak opioid. The remaining 24% (n=1470) did not receive any prescription analgesic.

The chance of receiving strong opioids was not affected by patients’ age or sex.

However, patients who died in a hospital were 60% less likely to have a prescription for strong opioids during the last year of life, when compared with those who died in hospice.

And patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than patients who did not receive chemotherapy.

Timing of therapy

Among the patients who did receive strong opioids, the median time between receiving the medication and death was 9 weeks. By 6 weeks before death, just 30% of patients had been prescribed a strong opioid.

The researchers noted that these figures don’t match up with previous studies reporting that severe pain can occur “much earlier in the cancer trajectory.”

Older patients were more likely to receive their strong opioid prescription late (defined as later than 9 weeks before death). After other factors were taken into account, patients age 60 or older were about 2 to 4 times more likely to be in the late-prescribing group, compared with those age 50 or younger.

Compared to patients who died in hospice, patients who died in a hospital were 40% more likely to receive a late prescription for a strong opioid. Patients who died in their own home were 2.6 times more likely to receive a late prescription, and patients who died in a care home were 2.8 times more likely to receive a late prescription.

Patients who had surgery were 40% more likely to receive a late prescription than patients who did not undergo surgery.

But patients who received chemotherapy and/or radiotherapy were 30% more likely to have received an early prescription for a strong opioid than patients who did not receive chemo/radiotherapy.

Dr Ziegler and her colleagues noted that this study had its limitations; in particular, the lack of data on pain severity.

Still, the researchers believe their results support the hypothesis of potential under-treatment of cancer pain and suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.

Doctor and patient in hospital

Photo courtesy of CDC

New research suggests that many patients who die of cancer do not receive strong opioid medications in their last year of life, despite the fact that these drugs are the recommended treatment for cancer-related pain.

Researchers used UK Cancer Registry Data to study more than 6000 cancer patients who died over a 7-year period.

Less than half of these patients received prescriptions for strong opioid medications in their last year of life.

Among those patients who did receive such prescriptions, many received them late.

Lucy Ziegler, PhD, of the University of Leeds in the UK, and her colleagues conducted this study and reported the results in PAIN.

The study included 6080 cancer patients who died between 2005 and 2012.

About 76% (n=4610) of these patients had received one or more prescriptions for analgesics, including 48% (n=2919) who received a strong opioid and 28% (n=1691) who received a non-opioid or weak opioid. The remaining 24% (n=1470) did not receive any prescription analgesic.

The chance of receiving strong opioids was not affected by patients’ age or sex.

However, patients who died in a hospital were 60% less likely to have a prescription for strong opioids during the last year of life, when compared with those who died in hospice.

And patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than patients who did not receive chemotherapy.

Timing of therapy

Among the patients who did receive strong opioids, the median time between receiving the medication and death was 9 weeks. By 6 weeks before death, just 30% of patients had been prescribed a strong opioid.

The researchers noted that these figures don’t match up with previous studies reporting that severe pain can occur “much earlier in the cancer trajectory.”

Older patients were more likely to receive their strong opioid prescription late (defined as later than 9 weeks before death). After other factors were taken into account, patients age 60 or older were about 2 to 4 times more likely to be in the late-prescribing group, compared with those age 50 or younger.

Compared to patients who died in hospice, patients who died in a hospital were 40% more likely to receive a late prescription for a strong opioid. Patients who died in their own home were 2.6 times more likely to receive a late prescription, and patients who died in a care home were 2.8 times more likely to receive a late prescription.

Patients who had surgery were 40% more likely to receive a late prescription than patients who did not undergo surgery.

But patients who received chemotherapy and/or radiotherapy were 30% more likely to have received an early prescription for a strong opioid than patients who did not receive chemo/radiotherapy.

Dr Ziegler and her colleagues noted that this study had its limitations; in particular, the lack of data on pain severity.

Still, the researchers believe their results support the hypothesis of potential under-treatment of cancer pain and suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.

B-cell precursor ALL

Image by Vashi Donsk

Adding rituximab to a chemotherapy regimen can improve event-free survival (EFS) in adults with newly diagnosed, CD20-positive acute lymphoblastic leukemia (ALL), according to the GRAALL-2005/R study.

The 2-year EFS was significantly higher for patients who received rituximab than for those who received chemotherapy alone.

However, there was no significant difference between the groups in 2-year overall survival.

Sébastien Maury, MD, PhD, of Hȏpital Hénri Mondor in Creteil, France, and his colleagues reported these results in NEJM. Results from this study were previously presented at the 2015 ASH Annual Meeting.

The study included 209 patients with newly diagnosed, Ph-negative, B-cell precursor ALL with 20% or more CD20-positive leukemic blasts.

The patients’ median age was 40.2 (range, 24.5–52.6), 13% had an ECOG performance status greater than 1, 6% had CNS involvement, and 21% had a white blood cell count of 30 x 10⁹/L or higher.

Half of the patients (n=104) were randomized to receive the GRAALL-2005 regimen, and the other half (n=105) were randomized to receive the same regimen plus rituximab. Details on the regimens are available in the supplementary material published with the NEJM paper.

Baseline patient characteristics were well-balanced between the treatment groups.

Results

At a median follow-up of 30 months, 101 patients (48%) had at least 1 event, including 44 (42%) in the rituximab group and 57 (55%) in the control group.

There were 17 induction failures (8 in the rituximab group and 9 in the control group), 57 relapses (22 and 35, respectively), and 27 deaths during remission (14 and 13, respectively). Two patients in the rituximab group were lost to follow-up during the first 12 months.

The 2-year EFS was significantly higher in the rituximab group than the control group—65% and 52%, respectively (hazard ratio [HR]=0.66, P=0.04).

However, the EFS benefit did not translate into a significant improvement in overall survival. The 2-year overall survival was 71% in the rituximab group and 64% in the control group (HR=0.70, P=0.10).

Similarly, the cumulative incidence of death during first remission was not significantly different between the treatment groups—12% for both (HR=0.98, P=0.96).

The researchers said the difference in EFS was mostly due to a lower incidence of relapse in the rituximab group. The 2-year incidence of relapse was 18% in the rituximab group and 32% in the control group (HR=0.52, P=0.02).

In a multivariate analysis, receiving the control treatment, older age, higher white blood cell count at baseline, and CNS involvement were all significantly associated with poor EFS.

There were 245 severe adverse events (AEs) reported in 124 patients—67 patients with 1 event, 26 with 2 events, 13 with 3 events, and 18 with 4 or more events.

The overall incidence of severe AEs did not differ significantly between the treatment groups—96% in the rituximab group and 92% in the control group.

Severe AEs included infection, laboratory abnormalities, allergic reactions, neurologic events, pulmonary events, coagulopathy, cardiac events, gastrointestinal events, and “other” events.

The only severe AE for which there was a significant difference between the treatment groups was allergic reactions. There were 2 severe allergic events in the rituximab group and 14 in the control group (P=0.002). Of these 16 events, all but 1 were due to asparaginase.

The researchers therefore theorized that rituximab might inhibit B-cell protection of antibodies against asparaginase, although they could not confirm this hypothesis.

B-cell precursor ALL

Image by Vashi Donsk

Adding rituximab to a chemotherapy regimen can improve event-free survival (EFS) in adults with newly diagnosed, CD20-positive acute lymphoblastic leukemia (ALL), according to the GRAALL-2005/R study.

The 2-year EFS was significantly higher for patients who received rituximab than for those who received chemotherapy alone.

However, there was no significant difference between the groups in 2-year overall survival.

Sébastien Maury, MD, PhD, of Hȏpital Hénri Mondor in Creteil, France, and his colleagues reported these results in NEJM. Results from this study were previously presented at the 2015 ASH Annual Meeting.

The study included 209 patients with newly diagnosed, Ph-negative, B-cell precursor ALL with 20% or more CD20-positive leukemic blasts.

The patients’ median age was 40.2 (range, 24.5–52.6), 13% had an ECOG performance status greater than 1, 6% had CNS involvement, and 21% had a white blood cell count of 30 x 10⁹/L or higher.

Half of the patients (n=104) were randomized to receive the GRAALL-2005 regimen, and the other half (n=105) were randomized to receive the same regimen plus rituximab. Details on the regimens are available in the supplementary material published with the NEJM paper.

Baseline patient characteristics were well-balanced between the treatment groups.

Results

At a median follow-up of 30 months, 101 patients (48%) had at least 1 event, including 44 (42%) in the rituximab group and 57 (55%) in the control group.

There were 17 induction failures (8 in the rituximab group and 9 in the control group), 57 relapses (22 and 35, respectively), and 27 deaths during remission (14 and 13, respectively). Two patients in the rituximab group were lost to follow-up during the first 12 months.

The 2-year EFS was significantly higher in the rituximab group than the control group—65% and 52%, respectively (hazard ratio [HR]=0.66, P=0.04).

However, the EFS benefit did not translate into a significant improvement in overall survival. The 2-year overall survival was 71% in the rituximab group and 64% in the control group (HR=0.70, P=0.10).

Similarly, the cumulative incidence of death during first remission was not significantly different between the treatment groups—12% for both (HR=0.98, P=0.96).

The researchers said the difference in EFS was mostly due to a lower incidence of relapse in the rituximab group. The 2-year incidence of relapse was 18% in the rituximab group and 32% in the control group (HR=0.52, P=0.02).

In a multivariate analysis, receiving the control treatment, older age, higher white blood cell count at baseline, and CNS involvement were all significantly associated with poor EFS.

There were 245 severe adverse events (AEs) reported in 124 patients—67 patients with 1 event, 26 with 2 events, 13 with 3 events, and 18 with 4 or more events.

The overall incidence of severe AEs did not differ significantly between the treatment groups—96% in the rituximab group and 92% in the control group.

Severe AEs included infection, laboratory abnormalities, allergic reactions, neurologic events, pulmonary events, coagulopathy, cardiac events, gastrointestinal events, and “other” events.

The only severe AE for which there was a significant difference between the treatment groups was allergic reactions. There were 2 severe allergic events in the rituximab group and 14 in the control group (P=0.002). Of these 16 events, all but 1 were due to asparaginase.

The researchers therefore theorized that rituximab might inhibit B-cell protection of antibodies against asparaginase, although they could not confirm this hypothesis.

B-cell precursor ALL

Image by Vashi Donsk

Adding rituximab to a chemotherapy regimen can improve event-free survival (EFS) in adults with newly diagnosed, CD20-positive acute lymphoblastic leukemia (ALL), according to the GRAALL-2005/R study.

The 2-year EFS was significantly higher for patients who received rituximab than for those who received chemotherapy alone.

However, there was no significant difference between the groups in 2-year overall survival.

Sébastien Maury, MD, PhD, of Hȏpital Hénri Mondor in Creteil, France, and his colleagues reported these results in NEJM. Results from this study were previously presented at the 2015 ASH Annual Meeting.

The study included 209 patients with newly diagnosed, Ph-negative, B-cell precursor ALL with 20% or more CD20-positive leukemic blasts.

The patients’ median age was 40.2 (range, 24.5–52.6), 13% had an ECOG performance status greater than 1, 6% had CNS involvement, and 21% had a white blood cell count of 30 x 10⁹/L or higher.

Half of the patients (n=104) were randomized to receive the GRAALL-2005 regimen, and the other half (n=105) were randomized to receive the same regimen plus rituximab. Details on the regimens are available in the supplementary material published with the NEJM paper.

Baseline patient characteristics were well-balanced between the treatment groups.

Results

At a median follow-up of 30 months, 101 patients (48%) had at least 1 event, including 44 (42%) in the rituximab group and 57 (55%) in the control group.

There were 17 induction failures (8 in the rituximab group and 9 in the control group), 57 relapses (22 and 35, respectively), and 27 deaths during remission (14 and 13, respectively). Two patients in the rituximab group were lost to follow-up during the first 12 months.

The 2-year EFS was significantly higher in the rituximab group than the control group—65% and 52%, respectively (hazard ratio [HR]=0.66, P=0.04).

However, the EFS benefit did not translate into a significant improvement in overall survival. The 2-year overall survival was 71% in the rituximab group and 64% in the control group (HR=0.70, P=0.10).

Similarly, the cumulative incidence of death during first remission was not significantly different between the treatment groups—12% for both (HR=0.98, P=0.96).

The researchers said the difference in EFS was mostly due to a lower incidence of relapse in the rituximab group. The 2-year incidence of relapse was 18% in the rituximab group and 32% in the control group (HR=0.52, P=0.02).

In a multivariate analysis, receiving the control treatment, older age, higher white blood cell count at baseline, and CNS involvement were all significantly associated with poor EFS.

There were 245 severe adverse events (AEs) reported in 124 patients—67 patients with 1 event, 26 with 2 events, 13 with 3 events, and 18 with 4 or more events.

The overall incidence of severe AEs did not differ significantly between the treatment groups—96% in the rituximab group and 92% in the control group.

Severe AEs included infection, laboratory abnormalities, allergic reactions, neurologic events, pulmonary events, coagulopathy, cardiac events, gastrointestinal events, and “other” events.

The only severe AE for which there was a significant difference between the treatment groups was allergic reactions. There were 2 severe allergic events in the rituximab group and 14 in the control group (P=0.002). Of these 16 events, all but 1 were due to asparaginase.

The researchers therefore theorized that rituximab might inhibit B-cell protection of antibodies against asparaginase, although they could not confirm this hypothesis.