Effect of midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non–small-cell lung cancer

A phase 2 clinical trial

Feng Ming Kong, Randall K. Ten Haken, Matthew Schipper, Kirk A. Frey, James Hayman, Milton Gross, Nithya Ramnath, Khaled A. Hassan, Martha Matuszak, Timothy Ritter, Nan Bi, Weili Wang, Mark Orringer, Kemp B. Cease, Theodore S. Lawrence, Gregory P. Kalemkerian

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

IMPORTANCE: Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE: To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION: Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES: The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS: The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively. CONCLUSIONS AND RELEVANCE: Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01190527.

Original languageEnglish (US)
Pages (from-to)1358-1365
Number of pages8
JournalJAMA Oncology
Volume3
Issue number10
DOIs
StatePublished - Oct 1 2017

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Non-Small Cell Lung Carcinoma
Radiotherapy
Clinical Trials
Drug Therapy
Neoplasms
Radiation
Lung
Emission-Computed Tomography
Survival
Carboplatin
Residual Neoplasm
Paclitaxel
Weight Loss
Survival Rate
Tomography
Oxygen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Effect of midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non–small-cell lung cancer : A phase 2 clinical trial. / Kong, Feng Ming; Ten Haken, Randall K.; Schipper, Matthew; Frey, Kirk A.; Hayman, James; Gross, Milton; Ramnath, Nithya; Hassan, Khaled A.; Matuszak, Martha; Ritter, Timothy; Bi, Nan; Wang, Weili; Orringer, Mark; Cease, Kemp B.; Lawrence, Theodore S.; Kalemkerian, Gregory P.

In: JAMA Oncology, Vol. 3, No. 10, 01.10.2017, p. 1358-1365.

Research output: Contribution to journalArticle

Kong, FM, Ten Haken, RK, Schipper, M, Frey, KA, Hayman, J, Gross, M, Ramnath, N, Hassan, KA, Matuszak, M, Ritter, T, Bi, N, Wang, W, Orringer, M, Cease, KB, Lawrence, TS & Kalemkerian, GP 2017, 'Effect of midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non–small-cell lung cancer: A phase 2 clinical trial', JAMA Oncology, vol. 3, no. 10, pp. 1358-1365. https://doi.org/10.1001/jamaoncol.2017.0982
Kong, Feng Ming ; Ten Haken, Randall K. ; Schipper, Matthew ; Frey, Kirk A. ; Hayman, James ; Gross, Milton ; Ramnath, Nithya ; Hassan, Khaled A. ; Matuszak, Martha ; Ritter, Timothy ; Bi, Nan ; Wang, Weili ; Orringer, Mark ; Cease, Kemp B. ; Lawrence, Theodore S. ; Kalemkerian, Gregory P. / Effect of midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non–small-cell lung cancer : A phase 2 clinical trial. In: JAMA Oncology. 2017 ; Vol. 3, No. 10. pp. 1358-1365.
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abstract = "IMPORTANCE: Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE: To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10{\%} weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION: Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES: The primary end point was local tumor control. The trial was designed to achieve a 20{\%} improvement in 2-year control from 34{\%} of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS: The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67{\%}); smoker or former smoker, 39 (93{\%}); stage III, 38 (90{\%}). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82{\%} (95{\%} CI, 62{\%}-92{\%}) and 62{\%} (95{\%} CI, 43{\%}-77{\%}), respectively. Median overall survival was 25 months (95{\%} CI, 12-32 months). The 2-year and 5-year overall survival rates were 52{\%} (95{\%} CI, 36{\%}-66{\%}) and 30{\%} (95{\%} CI, 16{\%}-45{\%}), respectively. CONCLUSIONS AND RELEVANCE: Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01190527.",
author = "Kong, {Feng Ming} and {Ten Haken}, {Randall K.} and Matthew Schipper and Frey, {Kirk A.} and James Hayman and Milton Gross and Nithya Ramnath and Hassan, {Khaled A.} and Martha Matuszak and Timothy Ritter and Nan Bi and Weili Wang and Mark Orringer and Cease, {Kemp B.} and Lawrence, {Theodore S.} and Kalemkerian, {Gregory P.}",
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TY - JOUR

T1 - Effect of midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non–small-cell lung cancer

T2 - A phase 2 clinical trial

AU - Kong, Feng Ming

AU - Ten Haken, Randall K.

AU - Schipper, Matthew

AU - Frey, Kirk A.

AU - Hayman, James

AU - Gross, Milton

AU - Ramnath, Nithya

AU - Hassan, Khaled A.

AU - Matuszak, Martha

AU - Ritter, Timothy

AU - Bi, Nan

AU - Wang, Weili

AU - Orringer, Mark

AU - Cease, Kemp B.

AU - Lawrence, Theodore S.

AU - Kalemkerian, Gregory P.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - IMPORTANCE: Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE: To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION: Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES: The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS: The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively. CONCLUSIONS AND RELEVANCE: Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01190527.

AB - IMPORTANCE: Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE: To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION: Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES: The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS: The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively. CONCLUSIONS AND RELEVANCE: Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01190527.

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