Neil Osterweil

ATLANTA – Patients with a positron-emission tomography–confirmed response to chemotherapy for Hodgkin’s lymphoma can be safely spared from radiotherapy without fear of compromising disease control, suggest results of studies presented at the annual meeting of the American Society of Hematology.

Among patients with Hodgkin’s lymphoma whose PET scans were negative for residual disease following three cycles of ABVD chemotherapy, the progression-free survival among patients who also received involved-field radiotherapy (IFRT) was 94.5% at a median of 48.6 months follow-up, compared with 90.8% of PET-negative patients who were not irradiated (intention-to-treat analysis), reported Dr. John Radford on behalf of the United Kingdom’s National Cancer Research Institute Lymphoma Clinical Studies Group.

"Using PET, it is possible to identify a population of patients with stages IA and IIA Hodgkin’s lymphoma who have an excellent outcome after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Crucially, however, these results have been obtained in the setting of, firstly, quality controlled PET image acquisition, secondly, central review of PET images at the core lab in London, and, thirdly, a comprehensive definition of ‘PET-negative,’ " said Dr. Radford.

He emphasized that longer follow-up is needed to determine what the effect of a PET-directed approach will be on 10- and 20-year survival and cause of death.

In a separate study, investigators led by Dr. Andrea Gallamini of San Croce General Hospital in Cuneo, Italy, found that the standard ABVD regimen is adequate therapy for PET-negative patients, and that the BEACOPP-escalated regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) was effective at rescuing PET-positive patients.

RAPID results

Dr. Radford reported results of the RAPID trial (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease).

The goal of the trial was to determine whether a negative PET scan is a good enough biomarker for response to therapy in patients with early-stage Hodgkin’s lymphoma to allow clinicians to safely omit IFRT.

They treated 602 adults with newly diagnosed Hodgkin’s lymphoma (139 of whom had stage IA disease and 281 with stage IIA disease) with three cycles of ABVD and then reassessed them for clinical response. Patients determined to have a response then underwent PET scans, and those who were PET positive went on to a fourth cycle of ABVD and IFRT. PET-negative patients were randomized to either IFRT at 30 Gy, or to no further treatment.

Of the 426 PET-negative patients, 420 were randomized – 209 to IFRT, and 211 to no additional therapy (3 patients chose not to be randomized, clinicians elected not to randomize 2, and 1 patient was not randomized due to an error).

Additionally, 25 PET-negative patients assigned to IFRT did not receive it, due to patient choice (19), deaths (5), or pneumonia (1).

In an intention-to-treat analysis, the hazard ratio for 3-year progression-free survival for PET-negative patients who also received IFRT was 1.51, but it was not statistically significant (P = .23)

In a per-protocol analysis of patients who received the allocated treatment (28 excluded for various reasons from the 420 randomized), the 3-year progression-free survival was 97% in the IFRT arm, and 90.7% in the no-further-treatment arm (HR in favor of IFRT 2.39, P equals .03). Dr. Radford noted, however, that in both the intention-to-treat and per-protocol analyses, the no-IFRT arm fell within the prespecified noninferiority margin.

Treatment intensification

Dr. Gallamini reported the first interim analysis of the GITIL/FIL (Gruppo Italiano Terapie Innovative Nei Linfomi/Fondazione Italiana Linfomi) HD0607 trial, in which patients with Hodgkin’s lymphoma who were PET positive after two cycles of ABVD were then randomized to escalated BEACOPP with or without rituximab. Patients who were PET negative continued on four additional cycles of ABVD.

Among 221 of 485 patients with at least 2-years of follow-up, the failure-free survival rate was 96.9% for patients who were PET negative after two cycles of ABVD compared with 82.7% for those who were PET negative (P less than .001)

"These results, although preliminary, show that a PET-adapted responsive treatment strategy is feasible in a multicenter prospective clinical trial, Dr. Gallamini said.

He added that the standard ABVD regimen appears to be sufficient for patients who are PET negative after two cycles.

The RAPID trial was supported by the UK National Health Service. Dr. Radford reported no relevant disclosures. The HD0607 trial is supported by the Italian Lymphoma Foundation. Dr. Gallamini reported serving on an advisory committee for Seattle Genetics Inc.

ATLANTA – Patients with a positron-emission tomography–confirmed response to chemotherapy for Hodgkin’s lymphoma can be safely spared from radiotherapy without fear of compromising disease control, suggest results of studies presented at the annual meeting of the American Society of Hematology.

Among patients with Hodgkin’s lymphoma whose PET scans were negative for residual disease following three cycles of ABVD chemotherapy, the progression-free survival among patients who also received involved-field radiotherapy (IFRT) was 94.5% at a median of 48.6 months follow-up, compared with 90.8% of PET-negative patients who were not irradiated (intention-to-treat analysis), reported Dr. John Radford on behalf of the United Kingdom’s National Cancer Research Institute Lymphoma Clinical Studies Group.

"Using PET, it is possible to identify a population of patients with stages IA and IIA Hodgkin’s lymphoma who have an excellent outcome after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Crucially, however, these results have been obtained in the setting of, firstly, quality controlled PET image acquisition, secondly, central review of PET images at the core lab in London, and, thirdly, a comprehensive definition of ‘PET-negative,’ " said Dr. Radford.

He emphasized that longer follow-up is needed to determine what the effect of a PET-directed approach will be on 10- and 20-year survival and cause of death.

In a separate study, investigators led by Dr. Andrea Gallamini of San Croce General Hospital in Cuneo, Italy, found that the standard ABVD regimen is adequate therapy for PET-negative patients, and that the BEACOPP-escalated regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) was effective at rescuing PET-positive patients.

RAPID results

Dr. Radford reported results of the RAPID trial (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease).

The goal of the trial was to determine whether a negative PET scan is a good enough biomarker for response to therapy in patients with early-stage Hodgkin’s lymphoma to allow clinicians to safely omit IFRT.

They treated 602 adults with newly diagnosed Hodgkin’s lymphoma (139 of whom had stage IA disease and 281 with stage IIA disease) with three cycles of ABVD and then reassessed them for clinical response. Patients determined to have a response then underwent PET scans, and those who were PET positive went on to a fourth cycle of ABVD and IFRT. PET-negative patients were randomized to either IFRT at 30 Gy, or to no further treatment.

Of the 426 PET-negative patients, 420 were randomized – 209 to IFRT, and 211 to no additional therapy (3 patients chose not to be randomized, clinicians elected not to randomize 2, and 1 patient was not randomized due to an error).

Additionally, 25 PET-negative patients assigned to IFRT did not receive it, due to patient choice (19), deaths (5), or pneumonia (1).

In an intention-to-treat analysis, the hazard ratio for 3-year progression-free survival for PET-negative patients who also received IFRT was 1.51, but it was not statistically significant (P = .23)

In a per-protocol analysis of patients who received the allocated treatment (28 excluded for various reasons from the 420 randomized), the 3-year progression-free survival was 97% in the IFRT arm, and 90.7% in the no-further-treatment arm (HR in favor of IFRT 2.39, P equals .03). Dr. Radford noted, however, that in both the intention-to-treat and per-protocol analyses, the no-IFRT arm fell within the prespecified noninferiority margin.

Treatment intensification

Dr. Gallamini reported the first interim analysis of the GITIL/FIL (Gruppo Italiano Terapie Innovative Nei Linfomi/Fondazione Italiana Linfomi) HD0607 trial, in which patients with Hodgkin’s lymphoma who were PET positive after two cycles of ABVD were then randomized to escalated BEACOPP with or without rituximab. Patients who were PET negative continued on four additional cycles of ABVD.

Among 221 of 485 patients with at least 2-years of follow-up, the failure-free survival rate was 96.9% for patients who were PET negative after two cycles of ABVD compared with 82.7% for those who were PET negative (P less than .001)

"These results, although preliminary, show that a PET-adapted responsive treatment strategy is feasible in a multicenter prospective clinical trial, Dr. Gallamini said.

He added that the standard ABVD regimen appears to be sufficient for patients who are PET negative after two cycles.

The RAPID trial was supported by the UK National Health Service. Dr. Radford reported no relevant disclosures. The HD0607 trial is supported by the Italian Lymphoma Foundation. Dr. Gallamini reported serving on an advisory committee for Seattle Genetics Inc.

ATLANTA – Patients with a positron-emission tomography–confirmed response to chemotherapy for Hodgkin’s lymphoma can be safely spared from radiotherapy without fear of compromising disease control, suggest results of studies presented at the annual meeting of the American Society of Hematology.

Among patients with Hodgkin’s lymphoma whose PET scans were negative for residual disease following three cycles of ABVD chemotherapy, the progression-free survival among patients who also received involved-field radiotherapy (IFRT) was 94.5% at a median of 48.6 months follow-up, compared with 90.8% of PET-negative patients who were not irradiated (intention-to-treat analysis), reported Dr. John Radford on behalf of the United Kingdom’s National Cancer Research Institute Lymphoma Clinical Studies Group.

"Using PET, it is possible to identify a population of patients with stages IA and IIA Hodgkin’s lymphoma who have an excellent outcome after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Crucially, however, these results have been obtained in the setting of, firstly, quality controlled PET image acquisition, secondly, central review of PET images at the core lab in London, and, thirdly, a comprehensive definition of ‘PET-negative,’ " said Dr. Radford.

He emphasized that longer follow-up is needed to determine what the effect of a PET-directed approach will be on 10- and 20-year survival and cause of death.

In a separate study, investigators led by Dr. Andrea Gallamini of San Croce General Hospital in Cuneo, Italy, found that the standard ABVD regimen is adequate therapy for PET-negative patients, and that the BEACOPP-escalated regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) was effective at rescuing PET-positive patients.

RAPID results

Dr. Radford reported results of the RAPID trial (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease).

The goal of the trial was to determine whether a negative PET scan is a good enough biomarker for response to therapy in patients with early-stage Hodgkin’s lymphoma to allow clinicians to safely omit IFRT.

They treated 602 adults with newly diagnosed Hodgkin’s lymphoma (139 of whom had stage IA disease and 281 with stage IIA disease) with three cycles of ABVD and then reassessed them for clinical response. Patients determined to have a response then underwent PET scans, and those who were PET positive went on to a fourth cycle of ABVD and IFRT. PET-negative patients were randomized to either IFRT at 30 Gy, or to no further treatment.

Of the 426 PET-negative patients, 420 were randomized – 209 to IFRT, and 211 to no additional therapy (3 patients chose not to be randomized, clinicians elected not to randomize 2, and 1 patient was not randomized due to an error).

Additionally, 25 PET-negative patients assigned to IFRT did not receive it, due to patient choice (19), deaths (5), or pneumonia (1).

In an intention-to-treat analysis, the hazard ratio for 3-year progression-free survival for PET-negative patients who also received IFRT was 1.51, but it was not statistically significant (P = .23)

In a per-protocol analysis of patients who received the allocated treatment (28 excluded for various reasons from the 420 randomized), the 3-year progression-free survival was 97% in the IFRT arm, and 90.7% in the no-further-treatment arm (HR in favor of IFRT 2.39, P equals .03). Dr. Radford noted, however, that in both the intention-to-treat and per-protocol analyses, the no-IFRT arm fell within the prespecified noninferiority margin.

Treatment intensification

Dr. Gallamini reported the first interim analysis of the GITIL/FIL (Gruppo Italiano Terapie Innovative Nei Linfomi/Fondazione Italiana Linfomi) HD0607 trial, in which patients with Hodgkin’s lymphoma who were PET positive after two cycles of ABVD were then randomized to escalated BEACOPP with or without rituximab. Patients who were PET negative continued on four additional cycles of ABVD.

Among 221 of 485 patients with at least 2-years of follow-up, the failure-free survival rate was 96.9% for patients who were PET negative after two cycles of ABVD compared with 82.7% for those who were PET negative (P less than .001)

"These results, although preliminary, show that a PET-adapted responsive treatment strategy is feasible in a multicenter prospective clinical trial, Dr. Gallamini said.

He added that the standard ABVD regimen appears to be sufficient for patients who are PET negative after two cycles.

The RAPID trial was supported by the UK National Health Service. Dr. Radford reported no relevant disclosures. The HD0607 trial is supported by the Italian Lymphoma Foundation. Dr. Gallamini reported serving on an advisory committee for Seattle Genetics Inc.

SAN JUAN, P.R. – Patients on prolonged ventilation who had previously failed a 5-day breathing challenge were weaned more rapidly off ventilators when a tracheostomy collar rather than pressure support was used, Dr. Amal Jubran reported.

Among 312 patients on prolonged ventilation (more than 21 days) transferred to a long-term acute care hospital, the median weaning time with unassisted breathing through tracheostomy collars was 4 days shorter than when pressure support was used as the weaning method, said Dr. Jubran of the division of pulmonary and critical care medicine at the Edward Hines Jr. VA Hospital in Hines, Ill.

"The method of ventilator weaning significantly improves the outcome of patients who require prolonged ventilation ... at a long-term care facility," she said at the annual congress of the Society of Critical Care Medicine.

The study findings were published simultaneously online in JAMA. There, the authors suggested that the more rapid weaning achieved with the use of the tracheostomy collar could be because the collar allows clinicians to directly observe whether patients are capable of breathing spontaneously (JAMA 2013 [doi:10.1001/jama.2013.159]).

"During a tracheostomy collar challenge, the amount of respiratory effort is determined solely by the patient. As such, observing a patient breathing through a tracheostomy collar provides the clinician with a clear view of the patient’s respiratory capabilities. In contrast, a clinician’s ability to judge weanability during pressure support is clouded because the patient is receiving ventilator assistance," the investigators wrote.

Clinicians may be more willing to wean patients who do better than expected on a trachesotomy challenge than they would patients who are on only low levels of pressure support, the authors suggested.

Weaning failures randomized

They based their conclusions on a decade-long randomized trial of patients with tracheotomies on prolonged ventilation who were transferred to a single center for weaning.

A total of 500 patients had a 5-day screening process during which they were given humidified oxygen through a tracheostomy collar and observed for signs of respiratory distress. Patients with no signs of distress during the challenge were considered to be weaned from ventilation and were excluded from the study, and the remaining 316 were randomly assigned to weaning with either a tracheostomy collar or pressure support. Patients in each study arm were stratified into one of four underlying disease categories, and to either early- or late-failure groups, based on the time it took for the breathing trial to fail (0 to less than 12 hours for early failures, 12-120 hours for late failures).

Ultimately, a total of 312 patients were included in the analysis.

Of the 160 patients in the tracheostomy collar group, 15 were deemed to be unweanable, 15 withdrew for various reasons, 16 died, and 10 were transferred to an acute care hospital. Of the remaining 104 patients in this arm, 85 (53.1% of the total group) were successfully weaned.

Of the 152 patients in the pressure support group, 21 were judged to be unweanable, 12 withdrew, 7 were transferred to an acute care hospital, and 22 died. Of the remaining 90 patients, 68 (45% of the total) were successfully weaned.

The median weaning time for patients on the collar was 15 (interquartile range [IQR], 8-25 days), compared with 19 days (IQR, 12-31 days) for patients on pressure support.

In an analysis adjusted for baseline clinical covariates, the hazard ratio (HR) favoring tracheostomy collar weaning was 1.43. Among patients in the late-failure subgroup, tracheostomy offered significantly more rapid weaning than did pressure support (HR, 3.33). There was no significant difference between the methods in time to weaning among patients who were deemed to be early screening failures, however. There were also no significant differences between weaning protocols in either 6- or 12-month mortality rates.

Dr. Jubran and colleagues acknowledged that their study was limited by the inability to fully mask treatment type from investigators (although investigators analyzing the data were blinded to protocol assignment), and by the use of single-center data, potentially limiting generalizability.

The study was supported by funding from the National Institute of Nursing Research. Dr. Jubran reported having no relevant financial disclosures.

SAN JUAN, P.R. – Patients on prolonged ventilation who had previously failed a 5-day breathing challenge were weaned more rapidly off ventilators when a tracheostomy collar rather than pressure support was used, Dr. Amal Jubran reported.

Among 312 patients on prolonged ventilation (more than 21 days) transferred to a long-term acute care hospital, the median weaning time with unassisted breathing through tracheostomy collars was 4 days shorter than when pressure support was used as the weaning method, said Dr. Jubran of the division of pulmonary and critical care medicine at the Edward Hines Jr. VA Hospital in Hines, Ill.

"The method of ventilator weaning significantly improves the outcome of patients who require prolonged ventilation ... at a long-term care facility," she said at the annual congress of the Society of Critical Care Medicine.

The study findings were published simultaneously online in JAMA. There, the authors suggested that the more rapid weaning achieved with the use of the tracheostomy collar could be because the collar allows clinicians to directly observe whether patients are capable of breathing spontaneously (JAMA 2013 [doi:10.1001/jama.2013.159]).

"During a tracheostomy collar challenge, the amount of respiratory effort is determined solely by the patient. As such, observing a patient breathing through a tracheostomy collar provides the clinician with a clear view of the patient’s respiratory capabilities. In contrast, a clinician’s ability to judge weanability during pressure support is clouded because the patient is receiving ventilator assistance," the investigators wrote.

Clinicians may be more willing to wean patients who do better than expected on a trachesotomy challenge than they would patients who are on only low levels of pressure support, the authors suggested.

Weaning failures randomized

They based their conclusions on a decade-long randomized trial of patients with tracheotomies on prolonged ventilation who were transferred to a single center for weaning.

A total of 500 patients had a 5-day screening process during which they were given humidified oxygen through a tracheostomy collar and observed for signs of respiratory distress. Patients with no signs of distress during the challenge were considered to be weaned from ventilation and were excluded from the study, and the remaining 316 were randomly assigned to weaning with either a tracheostomy collar or pressure support. Patients in each study arm were stratified into one of four underlying disease categories, and to either early- or late-failure groups, based on the time it took for the breathing trial to fail (0 to less than 12 hours for early failures, 12-120 hours for late failures).

Ultimately, a total of 312 patients were included in the analysis.

Of the 160 patients in the tracheostomy collar group, 15 were deemed to be unweanable, 15 withdrew for various reasons, 16 died, and 10 were transferred to an acute care hospital. Of the remaining 104 patients in this arm, 85 (53.1% of the total group) were successfully weaned.

Of the 152 patients in the pressure support group, 21 were judged to be unweanable, 12 withdrew, 7 were transferred to an acute care hospital, and 22 died. Of the remaining 90 patients, 68 (45% of the total) were successfully weaned.

The median weaning time for patients on the collar was 15 (interquartile range [IQR], 8-25 days), compared with 19 days (IQR, 12-31 days) for patients on pressure support.

In an analysis adjusted for baseline clinical covariates, the hazard ratio (HR) favoring tracheostomy collar weaning was 1.43. Among patients in the late-failure subgroup, tracheostomy offered significantly more rapid weaning than did pressure support (HR, 3.33). There was no significant difference between the methods in time to weaning among patients who were deemed to be early screening failures, however. There were also no significant differences between weaning protocols in either 6- or 12-month mortality rates.

Dr. Jubran and colleagues acknowledged that their study was limited by the inability to fully mask treatment type from investigators (although investigators analyzing the data were blinded to protocol assignment), and by the use of single-center data, potentially limiting generalizability.

The study was supported by funding from the National Institute of Nursing Research. Dr. Jubran reported having no relevant financial disclosures.

SAN JUAN, P.R. – Patients on prolonged ventilation who had previously failed a 5-day breathing challenge were weaned more rapidly off ventilators when a tracheostomy collar rather than pressure support was used, Dr. Amal Jubran reported.

Among 312 patients on prolonged ventilation (more than 21 days) transferred to a long-term acute care hospital, the median weaning time with unassisted breathing through tracheostomy collars was 4 days shorter than when pressure support was used as the weaning method, said Dr. Jubran of the division of pulmonary and critical care medicine at the Edward Hines Jr. VA Hospital in Hines, Ill.

"The method of ventilator weaning significantly improves the outcome of patients who require prolonged ventilation ... at a long-term care facility," she said at the annual congress of the Society of Critical Care Medicine.

The study findings were published simultaneously online in JAMA. There, the authors suggested that the more rapid weaning achieved with the use of the tracheostomy collar could be because the collar allows clinicians to directly observe whether patients are capable of breathing spontaneously (JAMA 2013 [doi:10.1001/jama.2013.159]).

"During a tracheostomy collar challenge, the amount of respiratory effort is determined solely by the patient. As such, observing a patient breathing through a tracheostomy collar provides the clinician with a clear view of the patient’s respiratory capabilities. In contrast, a clinician’s ability to judge weanability during pressure support is clouded because the patient is receiving ventilator assistance," the investigators wrote.

Clinicians may be more willing to wean patients who do better than expected on a trachesotomy challenge than they would patients who are on only low levels of pressure support, the authors suggested.

Weaning failures randomized

They based their conclusions on a decade-long randomized trial of patients with tracheotomies on prolonged ventilation who were transferred to a single center for weaning.

A total of 500 patients had a 5-day screening process during which they were given humidified oxygen through a tracheostomy collar and observed for signs of respiratory distress. Patients with no signs of distress during the challenge were considered to be weaned from ventilation and were excluded from the study, and the remaining 316 were randomly assigned to weaning with either a tracheostomy collar or pressure support. Patients in each study arm were stratified into one of four underlying disease categories, and to either early- or late-failure groups, based on the time it took for the breathing trial to fail (0 to less than 12 hours for early failures, 12-120 hours for late failures).

Ultimately, a total of 312 patients were included in the analysis.

Of the 160 patients in the tracheostomy collar group, 15 were deemed to be unweanable, 15 withdrew for various reasons, 16 died, and 10 were transferred to an acute care hospital. Of the remaining 104 patients in this arm, 85 (53.1% of the total group) were successfully weaned.

Of the 152 patients in the pressure support group, 21 were judged to be unweanable, 12 withdrew, 7 were transferred to an acute care hospital, and 22 died. Of the remaining 90 patients, 68 (45% of the total) were successfully weaned.

The median weaning time for patients on the collar was 15 (interquartile range [IQR], 8-25 days), compared with 19 days (IQR, 12-31 days) for patients on pressure support.

In an analysis adjusted for baseline clinical covariates, the hazard ratio (HR) favoring tracheostomy collar weaning was 1.43. Among patients in the late-failure subgroup, tracheostomy offered significantly more rapid weaning than did pressure support (HR, 3.33). There was no significant difference between the methods in time to weaning among patients who were deemed to be early screening failures, however. There were also no significant differences between weaning protocols in either 6- or 12-month mortality rates.

Dr. Jubran and colleagues acknowledged that their study was limited by the inability to fully mask treatment type from investigators (although investigators analyzing the data were blinded to protocol assignment), and by the use of single-center data, potentially limiting generalizability.

The study was supported by funding from the National Institute of Nursing Research. Dr. Jubran reported having no relevant financial disclosures.

SAN JUAN, P.R. – To extubate or to keep the patient on a ventilator? That is the question which, when answered by a respiratory therapy team before the next morning’s rounds began, halved the rate of ventilator-associated pneumonias and significantly decreased the time patients spent on ventilators in a surgical critical care unit, investigators reported at the annual Congress of the Society of Critical Care Medicine.

Previously, spontaneous breathing tests had occurred either during or after morning rounds, with extubations being left until sometime later in the day. Under the new protocol, however, respiratory therapists assigned exclusively to the surgical CCU conducted rounds three times daily, consulted with nurses and physicians, and performed spontaneous breathing tests as recommended under joint 2001 guidelines. Thus armed with the information, the multiprofessional team could make the final decision to extubate, and the extubation itself could occur at morning rounds, getting patients off the ventilator that much sooner, said Dr. Vijay Jayaraman, a resident in surgery at the Christiana Care Health System in Wilmington, Del.

Under the new protocol, Dr. Jayaraman and his colleagues saw the rate of ventilator-associated pneumonia (VAP) events decline from 10.8/1,000 ventilator days before the protocol was implemented, to 5.3/1,000 afterward (P less than .05). The mean time to start a spontaneous breathing trial dropped from 2.67 to 1.77 days (P = .004), and the time to extubation was shortened by a full day, 4.47 to 3.43 days (P = .033). There was no difference in days spent in the CCU post extubation, days spent on the patient floor after the CCU stay, or hospital length of stay, Dr. Jayaraman reported.

"This was established in a CCU that was already fully functioning with an active care team. It just required some reorganization, and the most important thing is that the respiratory therapist can be empowered to help us and actively drive the spontaneous breathing test and extubation process," he commented.

Dr. Juliana Barr, who moderated the session at which Dr, Jayaraman presented his study, commented that although myriad other groups have published ventilator-weaning protocols incorporating respiratory therapists, she was not aware of any studies that had previously shown a reduction in VAP rates.

"That was a low-hanging fruit study waiting for someone to do it, and I’m glad that you came along and did that. Thank you," she told Dr. Jayaraman. Dr. Barr is the acting medical director of critical care at the VA Palo Alto (Calif.) Health Care System.

The respiratory team uses predetermined criteria in a coordinated process consisting of awakening patients, performing the spontaneous breathing test, and, whenever possible, making the decision to extubate either before or during rounds.

For the study, the authors prospectively collected data on 180 patients admitted to their 28-bed level 1 surgical CCU from July through December 2010, before the protocol was implemented, and in 219 patients admitted over the same months in 2011, after the protocol had been in place for 6 months.

Extubate when the time is right

In a separate study, investigators from Montefiore Medical Center and other New York City institutions looked at whether outcomes following extubations in the CCU differed according to the time of day.

They retrospectively studied records of 2,240 patients on mechanical ventilation in 1 of 5 CCUs, and found that there were no significant differences in either 24-hour or 72-hour reintubation rates or in morality between patients extubated during daytime hours or during the night.

"Our data provides evidence that nighttime extubation is itself not associated with elevated risk of reintubation or mortality. Patients should be extubated when weaning parameters are met, irrespective of time of day, with appropriate staffing and resources," Dr. Bryan R. Tischenkel said in a poster presentation. Dr. Tischenkel is an anesthesia resident at New York Presbyterian Hospital.

Both studies were internally funded. Dr. Jayaraman, Dr. Barr, and and Dr. Tischenkel each reported having no relevant financial disclosures.

SAN JUAN, P.R. – To extubate or to keep the patient on a ventilator? That is the question which, when answered by a respiratory therapy team before the next morning’s rounds began, halved the rate of ventilator-associated pneumonias and significantly decreased the time patients spent on ventilators in a surgical critical care unit, investigators reported at the annual Congress of the Society of Critical Care Medicine.

Previously, spontaneous breathing tests had occurred either during or after morning rounds, with extubations being left until sometime later in the day. Under the new protocol, however, respiratory therapists assigned exclusively to the surgical CCU conducted rounds three times daily, consulted with nurses and physicians, and performed spontaneous breathing tests as recommended under joint 2001 guidelines. Thus armed with the information, the multiprofessional team could make the final decision to extubate, and the extubation itself could occur at morning rounds, getting patients off the ventilator that much sooner, said Dr. Vijay Jayaraman, a resident in surgery at the Christiana Care Health System in Wilmington, Del.

Under the new protocol, Dr. Jayaraman and his colleagues saw the rate of ventilator-associated pneumonia (VAP) events decline from 10.8/1,000 ventilator days before the protocol was implemented, to 5.3/1,000 afterward (P less than .05). The mean time to start a spontaneous breathing trial dropped from 2.67 to 1.77 days (P = .004), and the time to extubation was shortened by a full day, 4.47 to 3.43 days (P = .033). There was no difference in days spent in the CCU post extubation, days spent on the patient floor after the CCU stay, or hospital length of stay, Dr. Jayaraman reported.

"This was established in a CCU that was already fully functioning with an active care team. It just required some reorganization, and the most important thing is that the respiratory therapist can be empowered to help us and actively drive the spontaneous breathing test and extubation process," he commented.

Dr. Juliana Barr, who moderated the session at which Dr, Jayaraman presented his study, commented that although myriad other groups have published ventilator-weaning protocols incorporating respiratory therapists, she was not aware of any studies that had previously shown a reduction in VAP rates.

"That was a low-hanging fruit study waiting for someone to do it, and I’m glad that you came along and did that. Thank you," she told Dr. Jayaraman. Dr. Barr is the acting medical director of critical care at the VA Palo Alto (Calif.) Health Care System.

The respiratory team uses predetermined criteria in a coordinated process consisting of awakening patients, performing the spontaneous breathing test, and, whenever possible, making the decision to extubate either before or during rounds.

For the study, the authors prospectively collected data on 180 patients admitted to their 28-bed level 1 surgical CCU from July through December 2010, before the protocol was implemented, and in 219 patients admitted over the same months in 2011, after the protocol had been in place for 6 months.

Extubate when the time is right

In a separate study, investigators from Montefiore Medical Center and other New York City institutions looked at whether outcomes following extubations in the CCU differed according to the time of day.

They retrospectively studied records of 2,240 patients on mechanical ventilation in 1 of 5 CCUs, and found that there were no significant differences in either 24-hour or 72-hour reintubation rates or in morality between patients extubated during daytime hours or during the night.

"Our data provides evidence that nighttime extubation is itself not associated with elevated risk of reintubation or mortality. Patients should be extubated when weaning parameters are met, irrespective of time of day, with appropriate staffing and resources," Dr. Bryan R. Tischenkel said in a poster presentation. Dr. Tischenkel is an anesthesia resident at New York Presbyterian Hospital.

Both studies were internally funded. Dr. Jayaraman, Dr. Barr, and and Dr. Tischenkel each reported having no relevant financial disclosures.

SAN JUAN, P.R. – To extubate or to keep the patient on a ventilator? That is the question which, when answered by a respiratory therapy team before the next morning’s rounds began, halved the rate of ventilator-associated pneumonias and significantly decreased the time patients spent on ventilators in a surgical critical care unit, investigators reported at the annual Congress of the Society of Critical Care Medicine.

Previously, spontaneous breathing tests had occurred either during or after morning rounds, with extubations being left until sometime later in the day. Under the new protocol, however, respiratory therapists assigned exclusively to the surgical CCU conducted rounds three times daily, consulted with nurses and physicians, and performed spontaneous breathing tests as recommended under joint 2001 guidelines. Thus armed with the information, the multiprofessional team could make the final decision to extubate, and the extubation itself could occur at morning rounds, getting patients off the ventilator that much sooner, said Dr. Vijay Jayaraman, a resident in surgery at the Christiana Care Health System in Wilmington, Del.

Under the new protocol, Dr. Jayaraman and his colleagues saw the rate of ventilator-associated pneumonia (VAP) events decline from 10.8/1,000 ventilator days before the protocol was implemented, to 5.3/1,000 afterward (P less than .05). The mean time to start a spontaneous breathing trial dropped from 2.67 to 1.77 days (P = .004), and the time to extubation was shortened by a full day, 4.47 to 3.43 days (P = .033). There was no difference in days spent in the CCU post extubation, days spent on the patient floor after the CCU stay, or hospital length of stay, Dr. Jayaraman reported.

"This was established in a CCU that was already fully functioning with an active care team. It just required some reorganization, and the most important thing is that the respiratory therapist can be empowered to help us and actively drive the spontaneous breathing test and extubation process," he commented.

Dr. Juliana Barr, who moderated the session at which Dr, Jayaraman presented his study, commented that although myriad other groups have published ventilator-weaning protocols incorporating respiratory therapists, she was not aware of any studies that had previously shown a reduction in VAP rates.

"That was a low-hanging fruit study waiting for someone to do it, and I’m glad that you came along and did that. Thank you," she told Dr. Jayaraman. Dr. Barr is the acting medical director of critical care at the VA Palo Alto (Calif.) Health Care System.

The respiratory team uses predetermined criteria in a coordinated process consisting of awakening patients, performing the spontaneous breathing test, and, whenever possible, making the decision to extubate either before or during rounds.

For the study, the authors prospectively collected data on 180 patients admitted to their 28-bed level 1 surgical CCU from July through December 2010, before the protocol was implemented, and in 219 patients admitted over the same months in 2011, after the protocol had been in place for 6 months.

Extubate when the time is right

In a separate study, investigators from Montefiore Medical Center and other New York City institutions looked at whether outcomes following extubations in the CCU differed according to the time of day.

They retrospectively studied records of 2,240 patients on mechanical ventilation in 1 of 5 CCUs, and found that there were no significant differences in either 24-hour or 72-hour reintubation rates or in morality between patients extubated during daytime hours or during the night.

"Our data provides evidence that nighttime extubation is itself not associated with elevated risk of reintubation or mortality. Patients should be extubated when weaning parameters are met, irrespective of time of day, with appropriate staffing and resources," Dr. Bryan R. Tischenkel said in a poster presentation. Dr. Tischenkel is an anesthesia resident at New York Presbyterian Hospital.

Both studies were internally funded. Dr. Jayaraman, Dr. Barr, and and Dr. Tischenkel each reported having no relevant financial disclosures.

A healthy percentage of the morbidity, mortality, and costs associated with infections acquired in intensive care units are preventable by just following the rules, investigators said at the annual congress of the Society of Critical Care Medicine.

Interventions such as strict hand hygiene, meticulous attention to preinsertion disinfection of the patient’s skin, and the use of sterile dressings and drapes can dramatically reduce the incidence of catheter-related bloodstream infections (CRBSIs). Ventilator-associated pneumonia (VAP) can be prevented with precautions to avoid aspiration, reduction of upper airway colonization, and attention to sterilization of ventilatory equipment, said Dr. Alfred F. Connors Jr., senior associate dean of Case Western Reserve University, Cleveland.

Neil Osterweil/IMNG Medical Media

"These are two areas where we are at a really important turning point, where we can really make a difference and change the incidence of these infections in our patients," he said.

The key to making it all work is ensuring that staff adhere to best practices, said investigators from Sutter General Hospital in Sacramento. They reported that a physician-led multidisciplinary team charged with monitoring adherence to VAP prevention guidelines reduced the incidence of ventilator-associated infections from 17 out of 3,173 ventilator-days in 2004, to 2 in 12,694 ventilator-days from 2008 to 2011, a statistically significant reduction.

Protocols yes, compliance maybe

Dr. Connors noted that in a cross-sectional survey of 415 ICUs in 250 hospitals with a mean of 2.7 VAP infections per 1,000 ventilator-days, 68% of hospitals had a VAP bundle policy in place, but only 45% monitored compliance, and only 18% reported high compliance with the policy (Int. J. Qual. Health Care 2011;23:538-44).

"Unless you have a policy, you’re monitoring it, and you’re demonstrating high compliance, you won’t show any effect on your ventilator-associated pneumonia rate. There’s no magic to this. You can’t just say ‘Okay, we’ve got a policy, please follow it,’ and expect ventilator-associated pneumonia rates to drop; we have to intervene actively to get high compliance, and that’s easier said than done," he said.

At MetroHealth system in Cleveland, where Dr. Connors is chief medical officer, instituting and enforcing a stepped-up hand-hygiene program, isolation procedures, enhanced environmental cleaning, antibiotic stewardship, and implementation of evidence-based protocols for prevention of VAP, CRBSIs, and catheter-associated urinary tract infections resulted in an 18% decrease in antibiotic days of therapy from 2009 through the third quarter of 2012, and 32% decreases in both VAP and CRBSIs from 2010 to 2012.

More importantly, Dr. Connors said, such efforts save both lives and costs. He pointed to a 2011 study of national data on hospital-associated infections, which found that with proper infection control procedures, an estimated 44,762 to 164,127 central line–associated bloodstream infection (CLABSI) cases could be prevented, translating into 5,520 to 20,239 lives saved, and an estimated 95,078 to 137,613 preventable VAP cases, equivalent to 13,667 to 19,782 lives saved (Infect. Control Hosp. Epidemiol. 2011;32:101-14).

Team rounding cuts VAP

Dr. Saman Hayatdavoudi and colleagues at Sutter General Hospital made major inroads into reducing VAP rates through the creation of a multidisciplinary rounding team consisting of an intensivist, acute-care nurse practitioner (ACNP), respiratory therapist, clinical pharmacist, and bedside nurses.

The team made daily clinical rounds to verify whether clinicians were complying with hospital protocols and adhering to ventilator bundles, backed by a checklist.

"When deficiencies were noted, the ACNP was authorized to write orders bringing the care plans into best practice compliance," they wrote in a poster presentation.

As noted before, the team intervention reduced the incidence of VAP substantially, to just 2 per 12,694 ventilator-days, well below the benchmark of the 5.1 per 1,000 ventilator-days established by the Centers for Disease Control and Prevention’s National Healthcare Safety Network.

Dr. Connors reported having no financial disclosures. The study by Dr. Hayatdavoudi and colleagues was internally funded. The authors reported having no financial disclosures

A healthy percentage of the morbidity, mortality, and costs associated with infections acquired in intensive care units are preventable by just following the rules, investigators said at the annual congress of the Society of Critical Care Medicine.

Interventions such as strict hand hygiene, meticulous attention to preinsertion disinfection of the patient’s skin, and the use of sterile dressings and drapes can dramatically reduce the incidence of catheter-related bloodstream infections (CRBSIs). Ventilator-associated pneumonia (VAP) can be prevented with precautions to avoid aspiration, reduction of upper airway colonization, and attention to sterilization of ventilatory equipment, said Dr. Alfred F. Connors Jr., senior associate dean of Case Western Reserve University, Cleveland.

Neil Osterweil/IMNG Medical Media

"These are two areas where we are at a really important turning point, where we can really make a difference and change the incidence of these infections in our patients," he said.

The key to making it all work is ensuring that staff adhere to best practices, said investigators from Sutter General Hospital in Sacramento. They reported that a physician-led multidisciplinary team charged with monitoring adherence to VAP prevention guidelines reduced the incidence of ventilator-associated infections from 17 out of 3,173 ventilator-days in 2004, to 2 in 12,694 ventilator-days from 2008 to 2011, a statistically significant reduction.

Protocols yes, compliance maybe

Dr. Connors noted that in a cross-sectional survey of 415 ICUs in 250 hospitals with a mean of 2.7 VAP infections per 1,000 ventilator-days, 68% of hospitals had a VAP bundle policy in place, but only 45% monitored compliance, and only 18% reported high compliance with the policy (Int. J. Qual. Health Care 2011;23:538-44).

"Unless you have a policy, you’re monitoring it, and you’re demonstrating high compliance, you won’t show any effect on your ventilator-associated pneumonia rate. There’s no magic to this. You can’t just say ‘Okay, we’ve got a policy, please follow it,’ and expect ventilator-associated pneumonia rates to drop; we have to intervene actively to get high compliance, and that’s easier said than done," he said.

At MetroHealth system in Cleveland, where Dr. Connors is chief medical officer, instituting and enforcing a stepped-up hand-hygiene program, isolation procedures, enhanced environmental cleaning, antibiotic stewardship, and implementation of evidence-based protocols for prevention of VAP, CRBSIs, and catheter-associated urinary tract infections resulted in an 18% decrease in antibiotic days of therapy from 2009 through the third quarter of 2012, and 32% decreases in both VAP and CRBSIs from 2010 to 2012.

More importantly, Dr. Connors said, such efforts save both lives and costs. He pointed to a 2011 study of national data on hospital-associated infections, which found that with proper infection control procedures, an estimated 44,762 to 164,127 central line–associated bloodstream infection (CLABSI) cases could be prevented, translating into 5,520 to 20,239 lives saved, and an estimated 95,078 to 137,613 preventable VAP cases, equivalent to 13,667 to 19,782 lives saved (Infect. Control Hosp. Epidemiol. 2011;32:101-14).

Team rounding cuts VAP

Dr. Saman Hayatdavoudi and colleagues at Sutter General Hospital made major inroads into reducing VAP rates through the creation of a multidisciplinary rounding team consisting of an intensivist, acute-care nurse practitioner (ACNP), respiratory therapist, clinical pharmacist, and bedside nurses.

The team made daily clinical rounds to verify whether clinicians were complying with hospital protocols and adhering to ventilator bundles, backed by a checklist.

"When deficiencies were noted, the ACNP was authorized to write orders bringing the care plans into best practice compliance," they wrote in a poster presentation.

As noted before, the team intervention reduced the incidence of VAP substantially, to just 2 per 12,694 ventilator-days, well below the benchmark of the 5.1 per 1,000 ventilator-days established by the Centers for Disease Control and Prevention’s National Healthcare Safety Network.

Dr. Connors reported having no financial disclosures. The study by Dr. Hayatdavoudi and colleagues was internally funded. The authors reported having no financial disclosures

A healthy percentage of the morbidity, mortality, and costs associated with infections acquired in intensive care units are preventable by just following the rules, investigators said at the annual congress of the Society of Critical Care Medicine.

Interventions such as strict hand hygiene, meticulous attention to preinsertion disinfection of the patient’s skin, and the use of sterile dressings and drapes can dramatically reduce the incidence of catheter-related bloodstream infections (CRBSIs). Ventilator-associated pneumonia (VAP) can be prevented with precautions to avoid aspiration, reduction of upper airway colonization, and attention to sterilization of ventilatory equipment, said Dr. Alfred F. Connors Jr., senior associate dean of Case Western Reserve University, Cleveland.

Neil Osterweil/IMNG Medical Media

"These are two areas where we are at a really important turning point, where we can really make a difference and change the incidence of these infections in our patients," he said.

The key to making it all work is ensuring that staff adhere to best practices, said investigators from Sutter General Hospital in Sacramento. They reported that a physician-led multidisciplinary team charged with monitoring adherence to VAP prevention guidelines reduced the incidence of ventilator-associated infections from 17 out of 3,173 ventilator-days in 2004, to 2 in 12,694 ventilator-days from 2008 to 2011, a statistically significant reduction.

Protocols yes, compliance maybe

Dr. Connors noted that in a cross-sectional survey of 415 ICUs in 250 hospitals with a mean of 2.7 VAP infections per 1,000 ventilator-days, 68% of hospitals had a VAP bundle policy in place, but only 45% monitored compliance, and only 18% reported high compliance with the policy (Int. J. Qual. Health Care 2011;23:538-44).

"Unless you have a policy, you’re monitoring it, and you’re demonstrating high compliance, you won’t show any effect on your ventilator-associated pneumonia rate. There’s no magic to this. You can’t just say ‘Okay, we’ve got a policy, please follow it,’ and expect ventilator-associated pneumonia rates to drop; we have to intervene actively to get high compliance, and that’s easier said than done," he said.

At MetroHealth system in Cleveland, where Dr. Connors is chief medical officer, instituting and enforcing a stepped-up hand-hygiene program, isolation procedures, enhanced environmental cleaning, antibiotic stewardship, and implementation of evidence-based protocols for prevention of VAP, CRBSIs, and catheter-associated urinary tract infections resulted in an 18% decrease in antibiotic days of therapy from 2009 through the third quarter of 2012, and 32% decreases in both VAP and CRBSIs from 2010 to 2012.

More importantly, Dr. Connors said, such efforts save both lives and costs. He pointed to a 2011 study of national data on hospital-associated infections, which found that with proper infection control procedures, an estimated 44,762 to 164,127 central line–associated bloodstream infection (CLABSI) cases could be prevented, translating into 5,520 to 20,239 lives saved, and an estimated 95,078 to 137,613 preventable VAP cases, equivalent to 13,667 to 19,782 lives saved (Infect. Control Hosp. Epidemiol. 2011;32:101-14).

Team rounding cuts VAP

Dr. Saman Hayatdavoudi and colleagues at Sutter General Hospital made major inroads into reducing VAP rates through the creation of a multidisciplinary rounding team consisting of an intensivist, acute-care nurse practitioner (ACNP), respiratory therapist, clinical pharmacist, and bedside nurses.

The team made daily clinical rounds to verify whether clinicians were complying with hospital protocols and adhering to ventilator bundles, backed by a checklist.

"When deficiencies were noted, the ACNP was authorized to write orders bringing the care plans into best practice compliance," they wrote in a poster presentation.

As noted before, the team intervention reduced the incidence of VAP substantially, to just 2 per 12,694 ventilator-days, well below the benchmark of the 5.1 per 1,000 ventilator-days established by the Centers for Disease Control and Prevention’s National Healthcare Safety Network.

Dr. Connors reported having no financial disclosures. The study by Dr. Hayatdavoudi and colleagues was internally funded. The authors reported having no financial disclosures

ATLANTA  – In young patients with high-risk diffuse large B-cell lymphoma, autologous stem cell transplantation can push the rate of progression-free survival beyond that achievable with rituximab and high-dose chemotherapy.

But transplants did not appear to confer an overall survival advantage for these patients in a study of 399 patients, Dr. Umberto Vitolo reported at the annual meeting of the American Society of Hematology.

More than a decade ago, rituximab transformed the treatment of diffuse large B-cell lymphoma (DLBCL), and called into question the role of intensified high-dose chemotherapy and transplantation as first-line therapy. But poorer outcomes for young patients with high-risk disease prompted Dr. Vitolo, of the University Hospital in Turin, Italy, and his colleagues to see whether treatment intensification after rituximab dose-dense chemotherapy, delivered at two different levels, could reduce risk in younger patients.

In a prospective phase III trial of the Italian Lymphoma Foundation, previously untreated adults aged 18-65 years (median age 49 years) with DLBCL and an age-adjusted IPI (International Prognostic Index) score of 2 or 3 were randomized to receive one of four regimens:

• Eight cycles of R-CHOP14 (rituximab-cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine), prednisone).

• Six cycles of R-MegaCHOP14 (CHOP with a higher dose of cyclophosphamide).

• Four cycles of R-CHOP14 plus R-HDC (rituximab–high-dose chemotherapy) followed by BEAM (BCNU, etoposide, cytarabine, and melphalan) and ASTC (autologous stem-cell transplant).

• Four cycles of R-MegaCHOP14 plus R-HDC followed by BEAM and ASCT.

At a median of 41 months’ follow-up, 3-year progression-free survival was 75% among patients treated with the most intensive regimen of rituximab and high-dose chemotherapy followed by autologous stem-cell transplant. Three-year progression-free survival was 58% for the patients who got rituximab dose-dense chemotherapy (hazard ratio [HR], 0.63; P = .008).

There was no difference in overall survival, he said. Dose intensification in the chemotherapy-only arms did not offer additional benefit, and increased toxicities.

In all, 75% of 199 patients assigned to the two ASCT arms completed the trial, compared with 88% of 200 patients assigned to the two rituximab dose-dense only arms.

An intention-to-treat analysis showed that the combined complete response and complete response unconfirmed (CR/CRu) rates were 69% for the R-MegaCHOP14/ASCT arm, 82% for R-CHOP/ASCT, 73% for R-MegaCHOP14 only, and 71% for R-CHOP14 only. The respective partial response rates were 3%, 3%, 8%, and 13%, and nonresponse rates were 24%, 13%, 16%, and 15%.

A progression-free survival advantage was seen for the ASCT arms compared with the no-transplant arms. There was no significant difference in progression-free survival benefit in the chemotherapy only arms (65% for R-CHOP14, and 64% for R-MegaCHOP14; P = .73).

In an exploratory analysis comparing the four study arms with R-CHOP14 as the reference arm, R-CHOP14/ASCT only was associated with a significant reduction in risk of progression-free survival (HR, 0.56; confidence interval, 0.35-0.91).

Among intermediate to high-risk (age-adjusted IPI2) patients, 3-year progression-free survival was 75% for those treated with ASCT and 65% for those treated with chemotherapy only (HR, 0.63; P = .031). Among high-risk patients (IPI3), the respective rates were 60% and 46%, but the difference was not significant.

Among patients with any response (CR/CRu and PR) after four courses of chemotherapy, those who went on to transplant had a 3-year progression-free survival of 73%, compared with 62% for those who did not get a transplant (P = .018).

In multivariate analysis, the only significant prognostic factors were transplant, age at randomization, and bone marrow positive disease after treatment, said Dr. Vitolo.

Grade 3 or 4 hematologic toxicities were higher among patients in the transplant arms but were generally manageable, Dr. Vitolo said. The incidence of grade 3 febrile neutropenia was 2% among all transplant recipients, compared with 0.3% for nonrecipients; grade 4 events occurred in 0.2% vs. 0.08%, respectively. All patients had G-CSF (granulocyte colony-stimulating factor) support.

There were six treatment-related deaths (3%) among transplanted patients and four (2%) treatment-related deaths in the chemotherapy-only arms.

The study was supported by a grant from Compagnia SanPaolo/FIRMS, Turin. Dr. Vitolo disclosed serving in an advisory capacity to Roche, the marketer of rituximab.

ATLANTA  – In young patients with high-risk diffuse large B-cell lymphoma, autologous stem cell transplantation can push the rate of progression-free survival beyond that achievable with rituximab and high-dose chemotherapy.

But transplants did not appear to confer an overall survival advantage for these patients in a study of 399 patients, Dr. Umberto Vitolo reported at the annual meeting of the American Society of Hematology.

More than a decade ago, rituximab transformed the treatment of diffuse large B-cell lymphoma (DLBCL), and called into question the role of intensified high-dose chemotherapy and transplantation as first-line therapy. But poorer outcomes for young patients with high-risk disease prompted Dr. Vitolo, of the University Hospital in Turin, Italy, and his colleagues to see whether treatment intensification after rituximab dose-dense chemotherapy, delivered at two different levels, could reduce risk in younger patients.

In a prospective phase III trial of the Italian Lymphoma Foundation, previously untreated adults aged 18-65 years (median age 49 years) with DLBCL and an age-adjusted IPI (International Prognostic Index) score of 2 or 3 were randomized to receive one of four regimens:

• Eight cycles of R-CHOP14 (rituximab-cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine), prednisone).

• Six cycles of R-MegaCHOP14 (CHOP with a higher dose of cyclophosphamide).

• Four cycles of R-CHOP14 plus R-HDC (rituximab–high-dose chemotherapy) followed by BEAM (BCNU, etoposide, cytarabine, and melphalan) and ASTC (autologous stem-cell transplant).

• Four cycles of R-MegaCHOP14 plus R-HDC followed by BEAM and ASCT.

At a median of 41 months’ follow-up, 3-year progression-free survival was 75% among patients treated with the most intensive regimen of rituximab and high-dose chemotherapy followed by autologous stem-cell transplant. Three-year progression-free survival was 58% for the patients who got rituximab dose-dense chemotherapy (hazard ratio [HR], 0.63; P = .008).

There was no difference in overall survival, he said. Dose intensification in the chemotherapy-only arms did not offer additional benefit, and increased toxicities.

In all, 75% of 199 patients assigned to the two ASCT arms completed the trial, compared with 88% of 200 patients assigned to the two rituximab dose-dense only arms.

An intention-to-treat analysis showed that the combined complete response and complete response unconfirmed (CR/CRu) rates were 69% for the R-MegaCHOP14/ASCT arm, 82% for R-CHOP/ASCT, 73% for R-MegaCHOP14 only, and 71% for R-CHOP14 only. The respective partial response rates were 3%, 3%, 8%, and 13%, and nonresponse rates were 24%, 13%, 16%, and 15%.

A progression-free survival advantage was seen for the ASCT arms compared with the no-transplant arms. There was no significant difference in progression-free survival benefit in the chemotherapy only arms (65% for R-CHOP14, and 64% for R-MegaCHOP14; P = .73).

In an exploratory analysis comparing the four study arms with R-CHOP14 as the reference arm, R-CHOP14/ASCT only was associated with a significant reduction in risk of progression-free survival (HR, 0.56; confidence interval, 0.35-0.91).

Among intermediate to high-risk (age-adjusted IPI2) patients, 3-year progression-free survival was 75% for those treated with ASCT and 65% for those treated with chemotherapy only (HR, 0.63; P = .031). Among high-risk patients (IPI3), the respective rates were 60% and 46%, but the difference was not significant.

Among patients with any response (CR/CRu and PR) after four courses of chemotherapy, those who went on to transplant had a 3-year progression-free survival of 73%, compared with 62% for those who did not get a transplant (P = .018).

In multivariate analysis, the only significant prognostic factors were transplant, age at randomization, and bone marrow positive disease after treatment, said Dr. Vitolo.

Grade 3 or 4 hematologic toxicities were higher among patients in the transplant arms but were generally manageable, Dr. Vitolo said. The incidence of grade 3 febrile neutropenia was 2% among all transplant recipients, compared with 0.3% for nonrecipients; grade 4 events occurred in 0.2% vs. 0.08%, respectively. All patients had G-CSF (granulocyte colony-stimulating factor) support.

There were six treatment-related deaths (3%) among transplanted patients and four (2%) treatment-related deaths in the chemotherapy-only arms.

The study was supported by a grant from Compagnia SanPaolo/FIRMS, Turin. Dr. Vitolo disclosed serving in an advisory capacity to Roche, the marketer of rituximab.

ATLANTA  – In young patients with high-risk diffuse large B-cell lymphoma, autologous stem cell transplantation can push the rate of progression-free survival beyond that achievable with rituximab and high-dose chemotherapy.

But transplants did not appear to confer an overall survival advantage for these patients in a study of 399 patients, Dr. Umberto Vitolo reported at the annual meeting of the American Society of Hematology.

More than a decade ago, rituximab transformed the treatment of diffuse large B-cell lymphoma (DLBCL), and called into question the role of intensified high-dose chemotherapy and transplantation as first-line therapy. But poorer outcomes for young patients with high-risk disease prompted Dr. Vitolo, of the University Hospital in Turin, Italy, and his colleagues to see whether treatment intensification after rituximab dose-dense chemotherapy, delivered at two different levels, could reduce risk in younger patients.

In a prospective phase III trial of the Italian Lymphoma Foundation, previously untreated adults aged 18-65 years (median age 49 years) with DLBCL and an age-adjusted IPI (International Prognostic Index) score of 2 or 3 were randomized to receive one of four regimens:

• Eight cycles of R-CHOP14 (rituximab-cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine), prednisone).

• Six cycles of R-MegaCHOP14 (CHOP with a higher dose of cyclophosphamide).

• Four cycles of R-CHOP14 plus R-HDC (rituximab–high-dose chemotherapy) followed by BEAM (BCNU, etoposide, cytarabine, and melphalan) and ASTC (autologous stem-cell transplant).

• Four cycles of R-MegaCHOP14 plus R-HDC followed by BEAM and ASCT.

At a median of 41 months’ follow-up, 3-year progression-free survival was 75% among patients treated with the most intensive regimen of rituximab and high-dose chemotherapy followed by autologous stem-cell transplant. Three-year progression-free survival was 58% for the patients who got rituximab dose-dense chemotherapy (hazard ratio [HR], 0.63; P = .008).

There was no difference in overall survival, he said. Dose intensification in the chemotherapy-only arms did not offer additional benefit, and increased toxicities.

In all, 75% of 199 patients assigned to the two ASCT arms completed the trial, compared with 88% of 200 patients assigned to the two rituximab dose-dense only arms.

An intention-to-treat analysis showed that the combined complete response and complete response unconfirmed (CR/CRu) rates were 69% for the R-MegaCHOP14/ASCT arm, 82% for R-CHOP/ASCT, 73% for R-MegaCHOP14 only, and 71% for R-CHOP14 only. The respective partial response rates were 3%, 3%, 8%, and 13%, and nonresponse rates were 24%, 13%, 16%, and 15%.

A progression-free survival advantage was seen for the ASCT arms compared with the no-transplant arms. There was no significant difference in progression-free survival benefit in the chemotherapy only arms (65% for R-CHOP14, and 64% for R-MegaCHOP14; P = .73).

In an exploratory analysis comparing the four study arms with R-CHOP14 as the reference arm, R-CHOP14/ASCT only was associated with a significant reduction in risk of progression-free survival (HR, 0.56; confidence interval, 0.35-0.91).

Among intermediate to high-risk (age-adjusted IPI2) patients, 3-year progression-free survival was 75% for those treated with ASCT and 65% for those treated with chemotherapy only (HR, 0.63; P = .031). Among high-risk patients (IPI3), the respective rates were 60% and 46%, but the difference was not significant.

Among patients with any response (CR/CRu and PR) after four courses of chemotherapy, those who went on to transplant had a 3-year progression-free survival of 73%, compared with 62% for those who did not get a transplant (P = .018).

In multivariate analysis, the only significant prognostic factors were transplant, age at randomization, and bone marrow positive disease after treatment, said Dr. Vitolo.

Grade 3 or 4 hematologic toxicities were higher among patients in the transplant arms but were generally manageable, Dr. Vitolo said. The incidence of grade 3 febrile neutropenia was 2% among all transplant recipients, compared with 0.3% for nonrecipients; grade 4 events occurred in 0.2% vs. 0.08%, respectively. All patients had G-CSF (granulocyte colony-stimulating factor) support.

There were six treatment-related deaths (3%) among transplanted patients and four (2%) treatment-related deaths in the chemotherapy-only arms.

The study was supported by a grant from Compagnia SanPaolo/FIRMS, Turin. Dr. Vitolo disclosed serving in an advisory capacity to Roche, the marketer of rituximab.

ATLANTA – Lenalidomide, already an important agent in the treatment of multiple myeloma, is also flexing its muscles against non-Hodgkin’s lymphomas, reported researchers in two clinical trials presented at the annual meeting of the American Society for Hematology.

In a phase II study, lenalidomide (Revlimid) added to CHOP chemotherapy and rituximab (LR-CHOP21) produced a 92% overall response rate in elderly patients with untreated diffuse large B cell lymphoma (DLBCL), reported Dr. Annalisa Chiappella on behalf of the Italian Lymphoma Foundation in Alessandria, Italy.

"With a still limited follow-up, our data compare favorably with historical R-CHOP21 data, with a 2-year survival of 92% and a 2-year progression-free survival of 73%. LR-CHOP21 is able to induce a high 2-year progression-free survival of 65% also in poor-risk patients," Dr. Chiappella said.

In a separate study, single-agent lenalidomide also showed efficacy against relapsed/refractory mantle cell lymphoma (MCL), producing a 28% overall response rate for a median duration of 16.6 months, reported Dr. Andre Goy, chief of the lymphoma division at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center.

"This was a heavily pretreated population with a median of four prior therapies and a range of two to 10. Two-thirds were refractory to bortezomib [Velcade], more than half had a high tumor burden, one-third of the patients had bulky disease, and one-third had received prior transplants," Dr. Goy said.

CHOP add-on

In the Italian study, Dr. Chiappella and her colleagues looked at LR-CHOP21 in 49 patients (median age 69 years) with DLBCL. Nine of the patients had been treated with LR-CHOP21 at the maximum tolerated dose in phase I of the study.

The regimen consisted of six cycles of CHOP (cyclophosphamide, hydroxydaunomycin [doxorubicin], Oncovin [vincristine], and prednisone) plus rituximab at a dose of 375 mg/m², and lenalidomide at a dose of 15 mg daily on days 1-14 of each 21-day cycle.

Of the 294 total planned cycles of LR-CHOP21, 277 (94%) were administered. Some patients required a dose or a day reduction of lenalidomide, some received R-CHOP21 only, and some did not receive all planned cycles.

The final response, assessed after six cycles, included a complete response in 42 patients, a partial response in 3, no response in 3, and 1 death, for an overall response rate of 92%, At a median follow up of 22 months, the 2-year overall survival rate was 92%, which compares favorably with the 70% survival rate seen in historical controls treated with R-CHOP21 only, Dr. Chiappella said.

Of the four patient deaths, one was due to trauma, one to sepsis and multiple organ failure in a patient who had a complete response and had been off treatment for 6 months, one was due to heart failure, and one was from lymphoma progression.

The 2-year progression-free survival at 22 months’ median follow-up was 73%. The rate in R-CHOP21-treated historical controls was 57%.

Based on International Prognostic Index (IPI) risk, 2-year progression-free survival was 84% in patients with low- or intermediate-risk disease, and 65% in patients with intermediate/high-risk or high-risk disease.

Grade 3 or 4 adverse events in the per-protocol group included neutropenia (9% grade 3, 22% grade 4), febrile neutropenia (3%, 1%), leukocytopenia (15%, 13%), and thrombocytopenia (6%, 7%).

"These encouraging data warrant a future phase III randomized trial comparing LR-CHOP21 and R-CHOP21 in elderly patients with untreated DLBCL," Dr. Chiappella said.

MCL rescue

Dr. Goy and his colleagues looked at single-agent lenalidomide in patients with MCL who experienced disease relapse, progression, or who were refractory to bortezomib in the EMERGE trial (MCL-001 study).

In the phase II open-label study, 134 patients with MCL received lenalidomide 25 mg/day for 21 days out of every 28, with CT scans every two cycles until disease progression or unacceptable toxicities. The patients had to have failed prior anthracycline- or mitoxantrone-based therapy, cyclophosphamide, rituximab, and bortezomib.

The overall response rate by central review was 28%, with 8% of patients having a complete response or complete response unconfirmed (CR/CRu), 20% having a partial response, 29% having stable disease, and 26% experiencing disease progression.

The median time to response was 2.2 months, median time to CR/CRu was 3.7 months, median progression-free survival was 4 months, and median overall survival was 19 months at a median follow-up of 9.9 months. The median duration of response was more than 16 months, with the longest response more than 29 months at the time of data cutoff in July 2012.

The most common grade 3 or 4 adverse event was myelosuppression, consistent with the known safety profile of lenalidomide in non-Hodgkin’s lymphoma, Dr. Goy said.

Both Dr. Chiappella’s and Dr. Goy’s studies were supported in part by Celgene, maker of lenalidomide. Dr. Chiappella reported having no relevant disclosures. Dr. Goy is on Celgene’s speakers bureau.

ATLANTA – Lenalidomide, already an important agent in the treatment of multiple myeloma, is also flexing its muscles against non-Hodgkin’s lymphomas, reported researchers in two clinical trials presented at the annual meeting of the American Society for Hematology.

In a phase II study, lenalidomide (Revlimid) added to CHOP chemotherapy and rituximab (LR-CHOP21) produced a 92% overall response rate in elderly patients with untreated diffuse large B cell lymphoma (DLBCL), reported Dr. Annalisa Chiappella on behalf of the Italian Lymphoma Foundation in Alessandria, Italy.

"With a still limited follow-up, our data compare favorably with historical R-CHOP21 data, with a 2-year survival of 92% and a 2-year progression-free survival of 73%. LR-CHOP21 is able to induce a high 2-year progression-free survival of 65% also in poor-risk patients," Dr. Chiappella said.

In a separate study, single-agent lenalidomide also showed efficacy against relapsed/refractory mantle cell lymphoma (MCL), producing a 28% overall response rate for a median duration of 16.6 months, reported Dr. Andre Goy, chief of the lymphoma division at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center.

"This was a heavily pretreated population with a median of four prior therapies and a range of two to 10. Two-thirds were refractory to bortezomib [Velcade], more than half had a high tumor burden, one-third of the patients had bulky disease, and one-third had received prior transplants," Dr. Goy said.

CHOP add-on

In the Italian study, Dr. Chiappella and her colleagues looked at LR-CHOP21 in 49 patients (median age 69 years) with DLBCL. Nine of the patients had been treated with LR-CHOP21 at the maximum tolerated dose in phase I of the study.

The regimen consisted of six cycles of CHOP (cyclophosphamide, hydroxydaunomycin [doxorubicin], Oncovin [vincristine], and prednisone) plus rituximab at a dose of 375 mg/m², and lenalidomide at a dose of 15 mg daily on days 1-14 of each 21-day cycle.

Of the 294 total planned cycles of LR-CHOP21, 277 (94%) were administered. Some patients required a dose or a day reduction of lenalidomide, some received R-CHOP21 only, and some did not receive all planned cycles.

The final response, assessed after six cycles, included a complete response in 42 patients, a partial response in 3, no response in 3, and 1 death, for an overall response rate of 92%, At a median follow up of 22 months, the 2-year overall survival rate was 92%, which compares favorably with the 70% survival rate seen in historical controls treated with R-CHOP21 only, Dr. Chiappella said.

Of the four patient deaths, one was due to trauma, one to sepsis and multiple organ failure in a patient who had a complete response and had been off treatment for 6 months, one was due to heart failure, and one was from lymphoma progression.

The 2-year progression-free survival at 22 months’ median follow-up was 73%. The rate in R-CHOP21-treated historical controls was 57%.

Based on International Prognostic Index (IPI) risk, 2-year progression-free survival was 84% in patients with low- or intermediate-risk disease, and 65% in patients with intermediate/high-risk or high-risk disease.

Grade 3 or 4 adverse events in the per-protocol group included neutropenia (9% grade 3, 22% grade 4), febrile neutropenia (3%, 1%), leukocytopenia (15%, 13%), and thrombocytopenia (6%, 7%).

"These encouraging data warrant a future phase III randomized trial comparing LR-CHOP21 and R-CHOP21 in elderly patients with untreated DLBCL," Dr. Chiappella said.

MCL rescue

Dr. Goy and his colleagues looked at single-agent lenalidomide in patients with MCL who experienced disease relapse, progression, or who were refractory to bortezomib in the EMERGE trial (MCL-001 study).

In the phase II open-label study, 134 patients with MCL received lenalidomide 25 mg/day for 21 days out of every 28, with CT scans every two cycles until disease progression or unacceptable toxicities. The patients had to have failed prior anthracycline- or mitoxantrone-based therapy, cyclophosphamide, rituximab, and bortezomib.

The overall response rate by central review was 28%, with 8% of patients having a complete response or complete response unconfirmed (CR/CRu), 20% having a partial response, 29% having stable disease, and 26% experiencing disease progression.

The median time to response was 2.2 months, median time to CR/CRu was 3.7 months, median progression-free survival was 4 months, and median overall survival was 19 months at a median follow-up of 9.9 months. The median duration of response was more than 16 months, with the longest response more than 29 months at the time of data cutoff in July 2012.

The most common grade 3 or 4 adverse event was myelosuppression, consistent with the known safety profile of lenalidomide in non-Hodgkin’s lymphoma, Dr. Goy said.

Both Dr. Chiappella’s and Dr. Goy’s studies were supported in part by Celgene, maker of lenalidomide. Dr. Chiappella reported having no relevant disclosures. Dr. Goy is on Celgene’s speakers bureau.

ATLANTA – Lenalidomide, already an important agent in the treatment of multiple myeloma, is also flexing its muscles against non-Hodgkin’s lymphomas, reported researchers in two clinical trials presented at the annual meeting of the American Society for Hematology.

In a phase II study, lenalidomide (Revlimid) added to CHOP chemotherapy and rituximab (LR-CHOP21) produced a 92% overall response rate in elderly patients with untreated diffuse large B cell lymphoma (DLBCL), reported Dr. Annalisa Chiappella on behalf of the Italian Lymphoma Foundation in Alessandria, Italy.

"With a still limited follow-up, our data compare favorably with historical R-CHOP21 data, with a 2-year survival of 92% and a 2-year progression-free survival of 73%. LR-CHOP21 is able to induce a high 2-year progression-free survival of 65% also in poor-risk patients," Dr. Chiappella said.

In a separate study, single-agent lenalidomide also showed efficacy against relapsed/refractory mantle cell lymphoma (MCL), producing a 28% overall response rate for a median duration of 16.6 months, reported Dr. Andre Goy, chief of the lymphoma division at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center.

"This was a heavily pretreated population with a median of four prior therapies and a range of two to 10. Two-thirds were refractory to bortezomib [Velcade], more than half had a high tumor burden, one-third of the patients had bulky disease, and one-third had received prior transplants," Dr. Goy said.

CHOP add-on

In the Italian study, Dr. Chiappella and her colleagues looked at LR-CHOP21 in 49 patients (median age 69 years) with DLBCL. Nine of the patients had been treated with LR-CHOP21 at the maximum tolerated dose in phase I of the study.

The regimen consisted of six cycles of CHOP (cyclophosphamide, hydroxydaunomycin [doxorubicin], Oncovin [vincristine], and prednisone) plus rituximab at a dose of 375 mg/m², and lenalidomide at a dose of 15 mg daily on days 1-14 of each 21-day cycle.

Of the 294 total planned cycles of LR-CHOP21, 277 (94%) were administered. Some patients required a dose or a day reduction of lenalidomide, some received R-CHOP21 only, and some did not receive all planned cycles.

The final response, assessed after six cycles, included a complete response in 42 patients, a partial response in 3, no response in 3, and 1 death, for an overall response rate of 92%, At a median follow up of 22 months, the 2-year overall survival rate was 92%, which compares favorably with the 70% survival rate seen in historical controls treated with R-CHOP21 only, Dr. Chiappella said.

Of the four patient deaths, one was due to trauma, one to sepsis and multiple organ failure in a patient who had a complete response and had been off treatment for 6 months, one was due to heart failure, and one was from lymphoma progression.

The 2-year progression-free survival at 22 months’ median follow-up was 73%. The rate in R-CHOP21-treated historical controls was 57%.

Based on International Prognostic Index (IPI) risk, 2-year progression-free survival was 84% in patients with low- or intermediate-risk disease, and 65% in patients with intermediate/high-risk or high-risk disease.

Grade 3 or 4 adverse events in the per-protocol group included neutropenia (9% grade 3, 22% grade 4), febrile neutropenia (3%, 1%), leukocytopenia (15%, 13%), and thrombocytopenia (6%, 7%).

"These encouraging data warrant a future phase III randomized trial comparing LR-CHOP21 and R-CHOP21 in elderly patients with untreated DLBCL," Dr. Chiappella said.

MCL rescue

Dr. Goy and his colleagues looked at single-agent lenalidomide in patients with MCL who experienced disease relapse, progression, or who were refractory to bortezomib in the EMERGE trial (MCL-001 study).

In the phase II open-label study, 134 patients with MCL received lenalidomide 25 mg/day for 21 days out of every 28, with CT scans every two cycles until disease progression or unacceptable toxicities. The patients had to have failed prior anthracycline- or mitoxantrone-based therapy, cyclophosphamide, rituximab, and bortezomib.

The overall response rate by central review was 28%, with 8% of patients having a complete response or complete response unconfirmed (CR/CRu), 20% having a partial response, 29% having stable disease, and 26% experiencing disease progression.

The median time to response was 2.2 months, median time to CR/CRu was 3.7 months, median progression-free survival was 4 months, and median overall survival was 19 months at a median follow-up of 9.9 months. The median duration of response was more than 16 months, with the longest response more than 29 months at the time of data cutoff in July 2012.

The most common grade 3 or 4 adverse event was myelosuppression, consistent with the known safety profile of lenalidomide in non-Hodgkin’s lymphoma, Dr. Goy said.

Both Dr. Chiappella’s and Dr. Goy’s studies were supported in part by Celgene, maker of lenalidomide. Dr. Chiappella reported having no relevant disclosures. Dr. Goy is on Celgene’s speakers bureau.

BOSTON – Delivering stereotactic body radiation for early-stage, inoperable non–small cell lung cancer doubled overall survival rates achieved in historical series with conventional radiation, investigators reported at the annual meeting of the American Society for Radiation Oncology.

The 3-year overall survival rate reached 59.9% for 100 patients whose stage IA non–small cell lung cancer (NSCLC) was treated with stereotactic body radiation therapy (SBRT), said Dr. Yasushi Nagata. He compared results of the nonrandomized phase II trial with 31%-39% in historical series with conventional radiation.

The 5-year overall survival rate was 40.8%, compared with 13%-22.2% historically, added Dr. Nagata from Hiroshima University, Japan.

He described SBRT as well tolerated with only mild toxicities, making it a suitable alternative to other therapies, particularly in older patients. "Patients with early inoperable lung cancer should consider this treatment," Dr. Nagata advised in a briefing.

The investigators concluded that the treatment should be the new standard, replacing conventional radiotherapy in this population.

Similar in concept to stereotactic radiosurgery with a cyberknife, SBRT is a technique for precise high-dose targeting of tissues from multiple angles and planes, allowing delivery of much larger doses by fraction than conformal 3-dimensional or intensity-modulated radiation therapy. With SBRT, radiation therapy sessions can often be compressed into as little as 4-6 fractions delivered over 2 to 2.5 weeks, compared with 8 to 9 weeks of daily fractions for other techniques.

The phase II Japanese Clinical Oncology Group trial, JCOG-0403, is said to be the first to evaluate SBRT in both operable and nonoperable NSCLC. At the 2010 ASTRO annual meeting, the investigators reported 3-year survival rates for 64 patients with surgically resectable NSCLC: overall survival was 76%; progression-free survival, 54.5%; local progression-free survival, 68.5%; and event-free survival, 51.4%.

In the current study, 77 men and 27 women with a median age of 78 years (range 59-90 years) were enrolled; four patients were later excluded from the study, three because they developed a second primary cancer.

The median tumor size was 21 mm (range 9-30 mm). Fifty patients had adenocarcinomas, 40 had squamous cell carcinomas, and 14 had other tumor histologies. All patients had histologically or cytologically proven NSCLC, clinical T1N0M0 disease, and were determined by thoracic surgeons to be inoperable.

All patients completed the treatment protocol, consisting of a dose of 48 Gy at the isocenter divided into 4 fractions over 4-8 days.

The progression-free survival rate at 3 years was 49.8%; the local progression-free survival rate was 52.8%, and event-free survival, 46.8%.

Dr. Nagata and Dr. Chang disclosed no relevant conflicts.

BOSTON – Delivering stereotactic body radiation for early-stage, inoperable non–small cell lung cancer doubled overall survival rates achieved in historical series with conventional radiation, investigators reported at the annual meeting of the American Society for Radiation Oncology.

The 3-year overall survival rate reached 59.9% for 100 patients whose stage IA non–small cell lung cancer (NSCLC) was treated with stereotactic body radiation therapy (SBRT), said Dr. Yasushi Nagata. He compared results of the nonrandomized phase II trial with 31%-39% in historical series with conventional radiation.

The 5-year overall survival rate was 40.8%, compared with 13%-22.2% historically, added Dr. Nagata from Hiroshima University, Japan.

He described SBRT as well tolerated with only mild toxicities, making it a suitable alternative to other therapies, particularly in older patients. "Patients with early inoperable lung cancer should consider this treatment," Dr. Nagata advised in a briefing.

The investigators concluded that the treatment should be the new standard, replacing conventional radiotherapy in this population.

Similar in concept to stereotactic radiosurgery with a cyberknife, SBRT is a technique for precise high-dose targeting of tissues from multiple angles and planes, allowing delivery of much larger doses by fraction than conformal 3-dimensional or intensity-modulated radiation therapy. With SBRT, radiation therapy sessions can often be compressed into as little as 4-6 fractions delivered over 2 to 2.5 weeks, compared with 8 to 9 weeks of daily fractions for other techniques.

The phase II Japanese Clinical Oncology Group trial, JCOG-0403, is said to be the first to evaluate SBRT in both operable and nonoperable NSCLC. At the 2010 ASTRO annual meeting, the investigators reported 3-year survival rates for 64 patients with surgically resectable NSCLC: overall survival was 76%; progression-free survival, 54.5%; local progression-free survival, 68.5%; and event-free survival, 51.4%.

In the current study, 77 men and 27 women with a median age of 78 years (range 59-90 years) were enrolled; four patients were later excluded from the study, three because they developed a second primary cancer.

The median tumor size was 21 mm (range 9-30 mm). Fifty patients had adenocarcinomas, 40 had squamous cell carcinomas, and 14 had other tumor histologies. All patients had histologically or cytologically proven NSCLC, clinical T1N0M0 disease, and were determined by thoracic surgeons to be inoperable.

All patients completed the treatment protocol, consisting of a dose of 48 Gy at the isocenter divided into 4 fractions over 4-8 days.

The progression-free survival rate at 3 years was 49.8%; the local progression-free survival rate was 52.8%, and event-free survival, 46.8%.

Dr. Nagata and Dr. Chang disclosed no relevant conflicts.

BOSTON – Delivering stereotactic body radiation for early-stage, inoperable non–small cell lung cancer doubled overall survival rates achieved in historical series with conventional radiation, investigators reported at the annual meeting of the American Society for Radiation Oncology.

The 3-year overall survival rate reached 59.9% for 100 patients whose stage IA non–small cell lung cancer (NSCLC) was treated with stereotactic body radiation therapy (SBRT), said Dr. Yasushi Nagata. He compared results of the nonrandomized phase II trial with 31%-39% in historical series with conventional radiation.

The 5-year overall survival rate was 40.8%, compared with 13%-22.2% historically, added Dr. Nagata from Hiroshima University, Japan.

He described SBRT as well tolerated with only mild toxicities, making it a suitable alternative to other therapies, particularly in older patients. "Patients with early inoperable lung cancer should consider this treatment," Dr. Nagata advised in a briefing.

The investigators concluded that the treatment should be the new standard, replacing conventional radiotherapy in this population.

Similar in concept to stereotactic radiosurgery with a cyberknife, SBRT is a technique for precise high-dose targeting of tissues from multiple angles and planes, allowing delivery of much larger doses by fraction than conformal 3-dimensional or intensity-modulated radiation therapy. With SBRT, radiation therapy sessions can often be compressed into as little as 4-6 fractions delivered over 2 to 2.5 weeks, compared with 8 to 9 weeks of daily fractions for other techniques.

The phase II Japanese Clinical Oncology Group trial, JCOG-0403, is said to be the first to evaluate SBRT in both operable and nonoperable NSCLC. At the 2010 ASTRO annual meeting, the investigators reported 3-year survival rates for 64 patients with surgically resectable NSCLC: overall survival was 76%; progression-free survival, 54.5%; local progression-free survival, 68.5%; and event-free survival, 51.4%.

In the current study, 77 men and 27 women with a median age of 78 years (range 59-90 years) were enrolled; four patients were later excluded from the study, three because they developed a second primary cancer.

The median tumor size was 21 mm (range 9-30 mm). Fifty patients had adenocarcinomas, 40 had squamous cell carcinomas, and 14 had other tumor histologies. All patients had histologically or cytologically proven NSCLC, clinical T1N0M0 disease, and were determined by thoracic surgeons to be inoperable.

All patients completed the treatment protocol, consisting of a dose of 48 Gy at the isocenter divided into 4 fractions over 4-8 days.

The progression-free survival rate at 3 years was 49.8%; the local progression-free survival rate was 52.8%, and event-free survival, 46.8%.

Dr. Nagata and Dr. Chang disclosed no relevant conflicts.

Doximity. It’s an obvious mash-up of “doctors” and “proximity,” but it gets the point across. The “private network for physicians” hopes to do for clinicians what LinkedIn does for other professionals and Facebook does for the masses—connect like-minded people. Or in Doximity’s case, connect medical minds, the first step to professional sharing and collaboration and growing referral networks.

*Click on the links to the left of this introduction for a PDF of the full article and related Commentary.  

Doximity. It’s an obvious mash-up of “doctors” and “proximity,” but it gets the point across. The “private network for physicians” hopes to do for clinicians what LinkedIn does for other professionals and Facebook does for the masses—connect like-minded people. Or in Doximity’s case, connect medical minds, the first step to professional sharing and collaboration and growing referral networks.

*Click on the links to the left of this introduction for a PDF of the full article and related Commentary.  

Doximity. It’s an obvious mash-up of “doctors” and “proximity,” but it gets the point across. The “private network for physicians” hopes to do for clinicians what LinkedIn does for other professionals and Facebook does for the masses—connect like-minded people. Or in Doximity’s case, connect medical minds, the first step to professional sharing and collaboration and growing referral networks.

*Click on the links to the left of this introduction for a PDF of the full article and related Commentary.