Lobectomy shown safe after concurrent chemo and radiation

Lobectomy can be done safely after concurrent chemotherapy and high-dose radiation in patients with resectable N2-positive stage IIIA non–small cell lung cancer, according to study findings presented by Jessica S. Donington, MD.

Dr. Donington of New York University and her colleagues presented analysis of two prospective trials conducted by NRG Oncology, RTOG 0229 and RTOG 0839 at the AATS Annual Meeting. Both trials’ primary endpoints were mediastinal node sterilization after concurrent chemotherapy and full-dose radiation and those results were previously reported.  

Dr. Donington and her fellow investigators specifically examined short-term surgical outcomes, given the significant controversy regarding the safety of resection after full-dose thoracic radiation. In both trials, patients received weekly carboplatin and paclitaxel. Those in the 0229 trial underwent 61.2 Gy of radiation in 34 fractions, while patients in the 0839 trial underwent 60 Gy in 30 fractions. In addition, patients in the 0839 trial were randomized 2:1 to receive weekly panitumumab, an EGFR monoclonal antibody, with their induction therapy. 

Surgical expertise was considered essential to this treatment strategy. Therefore, all surgeons were certified by RTOG prior to enrolling patients, and all patients were surgically evaluated before beginning induction therapy to determine resectability and appropriateness for trimodality therapy.  Of 125 eligible patients enrolled in the two trials, 93 patients (74%) underwent anatomic resection. A total of 77 patients underwent lobectomy, 8 underwent pneumonectomy, 6 underwent bilobectomy, and 2 patients had sleeve lobectomy.

Medical contraindication and persistent nodal disease found during post-induction invasive staging were the most common reasons patients didn’t undergo resection. Eighty-five of the 93 surgical patients had R0 resections (91%). Surgeons attempted 14 minimally invasive resections (15%), 2 of which uneventfully converted to open resection. Just over one-quarter (28%) of patients suffered greater than Grade 3 adverse events (AEs) related to surgery, the majority of which were pulmonary in nature. 

The 30-day mortality rate was 4%, and all four deaths were linked to pulmonary adverse events, including acute respiratory distress syndrome, bronchopleural fistula, pulmonary artery hemorrhage, and respiratory failure. Multivariable analysis for mortality identified the addition of panitumumab and use of an extended resection to be associated with an increased risk for operative mortality. 
In the patients undergoing lobectomy, rates for greater than Grade 3 adverse events and 30-day mortality were 26%, and 1.3%, respectively. Those are similar to rates reported for lobectomy without induction therapy in the National Inpatient Sample (NIS) and the STS General Thoracic Surgery Database over the same time period.  

These two RTOG trials are the first to prospectively demonstrate that trimodality therapy with full-dose neoadjuvant radiation therapy is safe in a multi-institutional setting, Dr. Donington said. 

As her conclusions, she listed that “we have demonstrated the safety of resection following full-dose concurrent CRT in a multi-insitutional setting, that EGFR-AB and T2/T3 stage was associated with decreased nonfatal morbidity, but that extended resection and EGFR-AB were associated with excessive surgical mortality.” Dr. Donington added that the morbidity and mortality for lobectomy compared favorably with large national databases.She pointed out several limitations of the study, which included the relatively small size, and the unexpected toxicity of the EGFR antibody, “which severely limited our ability to assess trimodality therapy.”

She added that “our short-term outcomes tell us nothing about the long-term oncologic benefit. 

Dr. David R. Jones, chief of thoracic surgery at the Memorial Sloan-Kettering Cancer Center, New York, was the invited discussant of the paper. “Despite combining these [2] trials, there are still only 93 patients in the analysis and 77 of these had a lobectomy,” Dr. Jones stated. He pointed out that “there was a significant increase in 30- and 90-day mortality in the 16 patients who had more than a straightforward lobectomy,” and asked whether this increased mortality could be due to the use of radiation in the induction therapy.

Dr. Donington replied that there was a wide variation in causes of death, but that “the fact that these patients had induction therapy, be that radiation or chemo, and then went on to this bigger operation, it was overall a difficult thing for them to overcome.” Dr. Donington also agreed with a comment by Dr. Jones that it would be important to follow predicted postoperative diffusion capacity in these patients to potentially help determine the amount of lung to be taken and would be a valuable preoperative consideration.

Dr. Donington reported that two of her coauthors received grant support from NCI and AMGen for the work she was reporting, but that there were no other related disclosures.  Dr. Jones reported that he had no disclosures.

[email protected] 

Lobectomy can be done safely after concurrent chemotherapy and high-dose radiation in patients with resectable N2-positive stage IIIA non–small cell lung cancer, according to study findings presented by Jessica S. Donington, MD.

Dr. Donington of New York University and her colleagues presented analysis of two prospective trials conducted by NRG Oncology, RTOG 0229 and RTOG 0839 at the AATS Annual Meeting. Both trials’ primary endpoints were mediastinal node sterilization after concurrent chemotherapy and full-dose radiation and those results were previously reported.  

Dr. Donington and her fellow investigators specifically examined short-term surgical outcomes, given the significant controversy regarding the safety of resection after full-dose thoracic radiation. In both trials, patients received weekly carboplatin and paclitaxel. Those in the 0229 trial underwent 61.2 Gy of radiation in 34 fractions, while patients in the 0839 trial underwent 60 Gy in 30 fractions. In addition, patients in the 0839 trial were randomized 2:1 to receive weekly panitumumab, an EGFR monoclonal antibody, with their induction therapy. 

Surgical expertise was considered essential to this treatment strategy. Therefore, all surgeons were certified by RTOG prior to enrolling patients, and all patients were surgically evaluated before beginning induction therapy to determine resectability and appropriateness for trimodality therapy.  Of 125 eligible patients enrolled in the two trials, 93 patients (74%) underwent anatomic resection. A total of 77 patients underwent lobectomy, 8 underwent pneumonectomy, 6 underwent bilobectomy, and 2 patients had sleeve lobectomy.

Medical contraindication and persistent nodal disease found during post-induction invasive staging were the most common reasons patients didn’t undergo resection. Eighty-five of the 93 surgical patients had R0 resections (91%). Surgeons attempted 14 minimally invasive resections (15%), 2 of which uneventfully converted to open resection. Just over one-quarter (28%) of patients suffered greater than Grade 3 adverse events (AEs) related to surgery, the majority of which were pulmonary in nature. 

The 30-day mortality rate was 4%, and all four deaths were linked to pulmonary adverse events, including acute respiratory distress syndrome, bronchopleural fistula, pulmonary artery hemorrhage, and respiratory failure. Multivariable analysis for mortality identified the addition of panitumumab and use of an extended resection to be associated with an increased risk for operative mortality. 
In the patients undergoing lobectomy, rates for greater than Grade 3 adverse events and 30-day mortality were 26%, and 1.3%, respectively. Those are similar to rates reported for lobectomy without induction therapy in the National Inpatient Sample (NIS) and the STS General Thoracic Surgery Database over the same time period.  

These two RTOG trials are the first to prospectively demonstrate that trimodality therapy with full-dose neoadjuvant radiation therapy is safe in a multi-institutional setting, Dr. Donington said. 

As her conclusions, she listed that “we have demonstrated the safety of resection following full-dose concurrent CRT in a multi-insitutional setting, that EGFR-AB and T2/T3 stage was associated with decreased nonfatal morbidity, but that extended resection and EGFR-AB were associated with excessive surgical mortality.” Dr. Donington added that the morbidity and mortality for lobectomy compared favorably with large national databases.She pointed out several limitations of the study, which included the relatively small size, and the unexpected toxicity of the EGFR antibody, “which severely limited our ability to assess trimodality therapy.”

She added that “our short-term outcomes tell us nothing about the long-term oncologic benefit. 

Dr. David R. Jones, chief of thoracic surgery at the Memorial Sloan-Kettering Cancer Center, New York, was the invited discussant of the paper. “Despite combining these [2] trials, there are still only 93 patients in the analysis and 77 of these had a lobectomy,” Dr. Jones stated. He pointed out that “there was a significant increase in 30- and 90-day mortality in the 16 patients who had more than a straightforward lobectomy,” and asked whether this increased mortality could be due to the use of radiation in the induction therapy.

Dr. Donington replied that there was a wide variation in causes of death, but that “the fact that these patients had induction therapy, be that radiation or chemo, and then went on to this bigger operation, it was overall a difficult thing for them to overcome.” Dr. Donington also agreed with a comment by Dr. Jones that it would be important to follow predicted postoperative diffusion capacity in these patients to potentially help determine the amount of lung to be taken and would be a valuable preoperative consideration.

Dr. Donington reported that two of her coauthors received grant support from NCI and AMGen for the work she was reporting, but that there were no other related disclosures.  Dr. Jones reported that he had no disclosures.

[email protected] 

Lobectomy can be done safely after concurrent chemotherapy and high-dose radiation in patients with resectable N2-positive stage IIIA non–small cell lung cancer, according to study findings presented by Jessica S. Donington, MD.

Dr. Donington of New York University and her colleagues presented analysis of two prospective trials conducted by NRG Oncology, RTOG 0229 and RTOG 0839 at the AATS Annual Meeting. Both trials’ primary endpoints were mediastinal node sterilization after concurrent chemotherapy and full-dose radiation and those results were previously reported.  

Dr. Donington and her fellow investigators specifically examined short-term surgical outcomes, given the significant controversy regarding the safety of resection after full-dose thoracic radiation. In both trials, patients received weekly carboplatin and paclitaxel. Those in the 0229 trial underwent 61.2 Gy of radiation in 34 fractions, while patients in the 0839 trial underwent 60 Gy in 30 fractions. In addition, patients in the 0839 trial were randomized 2:1 to receive weekly panitumumab, an EGFR monoclonal antibody, with their induction therapy. 

Surgical expertise was considered essential to this treatment strategy. Therefore, all surgeons were certified by RTOG prior to enrolling patients, and all patients were surgically evaluated before beginning induction therapy to determine resectability and appropriateness for trimodality therapy.  Of 125 eligible patients enrolled in the two trials, 93 patients (74%) underwent anatomic resection. A total of 77 patients underwent lobectomy, 8 underwent pneumonectomy, 6 underwent bilobectomy, and 2 patients had sleeve lobectomy.

Medical contraindication and persistent nodal disease found during post-induction invasive staging were the most common reasons patients didn’t undergo resection. Eighty-five of the 93 surgical patients had R0 resections (91%). Surgeons attempted 14 minimally invasive resections (15%), 2 of which uneventfully converted to open resection. Just over one-quarter (28%) of patients suffered greater than Grade 3 adverse events (AEs) related to surgery, the majority of which were pulmonary in nature. 

The 30-day mortality rate was 4%, and all four deaths were linked to pulmonary adverse events, including acute respiratory distress syndrome, bronchopleural fistula, pulmonary artery hemorrhage, and respiratory failure. Multivariable analysis for mortality identified the addition of panitumumab and use of an extended resection to be associated with an increased risk for operative mortality. 
In the patients undergoing lobectomy, rates for greater than Grade 3 adverse events and 30-day mortality were 26%, and 1.3%, respectively. Those are similar to rates reported for lobectomy without induction therapy in the National Inpatient Sample (NIS) and the STS General Thoracic Surgery Database over the same time period.  

These two RTOG trials are the first to prospectively demonstrate that trimodality therapy with full-dose neoadjuvant radiation therapy is safe in a multi-institutional setting, Dr. Donington said. 

As her conclusions, she listed that “we have demonstrated the safety of resection following full-dose concurrent CRT in a multi-insitutional setting, that EGFR-AB and T2/T3 stage was associated with decreased nonfatal morbidity, but that extended resection and EGFR-AB were associated with excessive surgical mortality.” Dr. Donington added that the morbidity and mortality for lobectomy compared favorably with large national databases.She pointed out several limitations of the study, which included the relatively small size, and the unexpected toxicity of the EGFR antibody, “which severely limited our ability to assess trimodality therapy.”

She added that “our short-term outcomes tell us nothing about the long-term oncologic benefit. 

Dr. David R. Jones, chief of thoracic surgery at the Memorial Sloan-Kettering Cancer Center, New York, was the invited discussant of the paper. “Despite combining these [2] trials, there are still only 93 patients in the analysis and 77 of these had a lobectomy,” Dr. Jones stated. He pointed out that “there was a significant increase in 30- and 90-day mortality in the 16 patients who had more than a straightforward lobectomy,” and asked whether this increased mortality could be due to the use of radiation in the induction therapy.

Dr. Donington replied that there was a wide variation in causes of death, but that “the fact that these patients had induction therapy, be that radiation or chemo, and then went on to this bigger operation, it was overall a difficult thing for them to overcome.” Dr. Donington also agreed with a comment by Dr. Jones that it would be important to follow predicted postoperative diffusion capacity in these patients to potentially help determine the amount of lung to be taken and would be a valuable preoperative consideration.

Dr. Donington reported that two of her coauthors received grant support from NCI and AMGen for the work she was reporting, but that there were no other related disclosures.  Dr. Jones reported that he had no disclosures.

[email protected]