Rtog 0617 trial

Treatment assignment and patient characteristics by RT technique were summarized and compared Table 1. The lung V20 was not different between groups median, With a median follow-up of On multivariable analysis Table 5 , IMRT remained associated with a statistically significant reduction in pneumonitis risk odds ratio, 0. There were similar rates of treatment interruptions due to adverse effects or illness Moreover, IMRT was able to reduce radiation doses delivered to the heart, and heart doses were highly associated with OS on multivariable analysis.

The lung V20 is a classic and the most frequently described dosimetric parameter believed to be a threshold dose that predicts probability of lung injury.

Moreover, these results argue against using the lung V5 for IMRT plan optimization because an attempt to lower the V5 can potentially lead to less conformity of the high-dose region and an inability to reduce intermediate dose V20 , both of which were important objectives confirmed in this study. Patients treated with IMRT were less likely to have completed high school or attain education beyond high school. We speculate that worse socioeconomic circumstances may account for the larger tumor volumes and more advanced-stage tumors seen in the IMRT group possibly due to barriers to health care access, which leads to later diagnoses.

Despite indications that patients in the IMRT group had worse socioeconomic circumstances, these patients had a notably better severe toxicity profile, and OS was not different from that of the 3D-CRT group. IMRT could have mitigated a possible negative impact that socioeconomic status might have otherwise had on survival and coordination of care.

The dose of radiation to the heart was shown to be an important predictor of survival in NRG Oncology clinical trial RTOG , 23 and this secondary analysis shows that IMRT is able to significantly reduce radiation doses delivered to the heart. Although this study was not designed to determine the survival impact of radiation doses to the heart, IMRT possibly mitigated the potential adverse survival effect conferred by larger and more advanced tumors by reducing radiation doses to the heart, such as the V40, which accounts for similar survival between the 3D-CRT and IMRT groups.

However, longer follow-up may be needed to capture differences in cardiac toxicity associated with IMRT. Although institutional accrual status was previously shown to be associated with survival outcomes in NRG Oncology clinical trial RTOG patients, 34 the heart V40 remains significantly associated with OS on multivariable analysis, even with adjustment for institutional accrual status.

Further pending analyses of heart doses in NRG Oncology clinical trial RTOG may provide critical insights into the effect of radiation doses on specific anatomic regions of the heart as well as pertinent heart radiation dose constraints. By reducing severe grade 3 or greater pneumonitis risks and lowering heart doses, IMRT may eventually be associated with improved OS on long-term follow-up.

IMRT should be used routinely for locally advanced NSCLC to allow greater tailoring of the conformity of the radiation dose distribution to patient anatomy. Supported by Grants No. Conception and design: Stephen G. Komaki, Robert D. Timmerman, Jeffrey A. Bogart, Michael C.

Dobelbower, James M. Galvin, Jeffrey D. Provision of study materials or patients: Raymond B. Wynn, Robert M. Collection and assembly of data: Chen Hu, Robert D. Timmerman, Steven E. Schild, Walter Bosch, Vivek S. Kavadi, Raymond B. Wynn, Adam Raben, Mark E. Augspurger, Robert M. Data analysis and interpretation: Stephen G.

Chun, Chen Hu, Robert D. Schild, Vivek S. Robinson, Raymond B. Accountable for all aspects of the work: All authors. The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www. National Center for Biotechnology Information , U.

J Clin Oncol. Published online Oct 3. Komaki , Robert D. Timmerman , Steven E. Schild , Jeffrey A. Bogart , Michael C.

Dobelbower , Walter Bosch , James M. Galvin , Vivek S. Robinson , Raymond B. Wynn , Adam Raben , Mark E. Augspurger , Robert M. Chun Stephen G. Find articles by Stephen G. Chen Hu Stephen G. Find articles by Chen Hu. Hak Choy Stephen G. Find articles by Hak Choy.

Ritsuko U. Komaki Stephen G. Find articles by Ritsuko U. Robert D. Timmerman Stephen G. Find articles by Robert D. Steven E. Schild Stephen G. Find articles by Steven E. Jeffrey A. Bogart Stephen G. Find articles by Jeffrey A. Michael C. Dobelbower Stephen G.

Find articles by Michael C. Walter Bosch Stephen G. Find articles by Walter Bosch. James M. Galvin Stephen G. Find articles by James M. Vivek S. Kavadi Stephen G. Find articles by Vivek S. Samir Narayan Stephen G. Find articles by Samir Narayan.

Puneeth Iyengar Stephen G. Find articles by Puneeth Iyengar. Clifford G. Robinson Stephen G. Find articles by Clifford G. Raymond B. Wynn Stephen G. Find articles by Raymond B. Adam Raben Stephen G. Find articles by Adam Raben.

Mark E. Augspurger Stephen G. Find articles by Mark E. Robert M. MacRae Stephen G. Find articles by Robert M. Listing a study does not mean it has been evaluated by the U. Federal Government. Read our disclaimer for details. Recruitment status was: Active, not recruiting First Posted : September 24, Results First Posted : May 5, Last Update Posted : February 5, Study Description.

Detailed Description:. To compare the overall survival of patients treated with versus without cetuximab in the setting of concurrent chemotherapy Secondary To compare progression-free survival and local-regional tumor control in patients treated with these regimens. To compare the toxicity of high- versus standard-dose conformal radiotherapy and concurrent chemotherapy with versus without cetuximab in these patients.

To investigate the prognostic and predictive effects of gross tumor volume on overall survival of patients treated with these regimens. To compare the quality of life of patients treated with these regimens. To correlate outcomes i. To analyze the predictive value of pre-treatment standardized uptake value SUV of positron emission tomography PET scan in predicting survival, distant metastasis, and local-regional control in patients treated with these regimens.

To explore biological markers to predict clinical outcome including survival, distant metastasis, local-regional control, and QOL including toxicity in patients treated with these regimens.

To prospectively collect and bank tissue, blood, and urine specimens for future biomarker analyses in predicting clinical outcome in patients treated with these regimens.

To investigate associations between epidermal growth factor receptor EGFR expression and toxicity, response, overall survival, and progression-free survival. MedlinePlus related topics: Lung Cancer. Drug Information available for: Paclitaxel Carboplatin Cetuximab.

FDA Resources. Arms and Interventions. Other Names: Taxol Abraxane. Radiation therapy RT in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks. Radiation therapy RT in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7. Outcome Measures. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was Patients last known to be alive are censored at the date of last contact.

Time is measured from the date of randomization to the date of first failure. Patients without failure are censored at the date of last follow-up. A failure for local-regional failure is the first occurrence of local or regional progression. Patients alive without local or regional failure at the time of last follow-up are censored.

Patients who died without local or regional failure are considered as having competing risk at the time of death. Local-regional failure was estimated by the cumulative incidence method and 2 year estimates are reported.

Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy. Treatment-related adverse events other than esophagitis and pneumonitis were assessed graded using the CTCAE v3. Deaths regardless of cause and occuring during or within 30 days of discontinuation of protocol treatment were evaluated.

A decline of 2 points in the LCS from baseline to 3 months was considered a clinically meaningful change indicating a decline in quality of life.

Patients completed a swallowing diary prior to the start of treatment and then daily during treatment. Patients recorded a score to indicate problems with swallowing on that day 1-None, 2-Mild soreness only, 3-Can swallow solids with some difficulty, 4-Cannot swallow solids, 5-Cannot swallow liquids.

These scores were then plotted across time and the area under the curve from baseline until the end of week 6 was calculated. A lower area under the curve indicates better swallowing ability. The visual analogue scale is a self-assessment of current health state, measured on a cm scale ranging from 0 for the worst imaginable health state to for best imaginable health state, marked at point intervals.

The area under the curve of each subject's EQ5D visual analog scale VAS response trajectory within 1 year was calculated. The trajectory included all available time points through one year.

If subject was censored within one year, the EQ5D utility curve was truncated at the time of censoring. The scores were plotted across time and the area under the curve was calculated. A greater area under the curve indicates a better health state. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation. EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells.

Patients were divided into two groups based on H-Score values dichotomized at All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method.

A local-regional event is the first development of progressive disease locally or regionally, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are reported. Worst toxicity as determined by adverse events was used as a measure of a patient's quality of life QOL. Grade refers to the severity of the AE. Highest grade worst adverse event AE per subject was counted. Gross tumor volume GTV is defined as the combined volume cubic centimeters of the primary tumor and clinically positive lymph nodes seen either on the planning computed tomography CT scan or the pretreatment positron emission tomography PET scan.

Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. It is a mathematically derived ratio of tissue radioactivity concentration at a point in time and the injected dose of radioactivity per kilogram of the patient's body weight.

Two-year rates are presented. Eligibility Criteria. Patients must be considered unresectable or inoperable; Note: Patients who have had a nodal recurrence after surgery for an early-stage NSCLC are eligible if the following criteria are met: Nodal recurrence must be N1 or N2; N3 is not eligible. The initial primary must have been staged as T, N0, M0.

The node must be biopsied within 12 weeks of registration. The node must be measurable. The patient must not have received prior chemotherapy or radiation for this lung cancer. Prior curative surgery must have been at least 6 months prior to the nodal recurrence. The exception to a prior invasive malignancy does not apply to the initial lung primary. An MRI without contrast is only permitted if the patient has a contrast allergy.

If a pleural effusion is present, the following criteria must be met to exclude malignant involvement incurable T4 disease : When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative. Exudative pleural effusions are excluded, regardless of cytology; Effusions that are minimal i. Patients must have measurable or evaluable disease.

Patients with post-obstructive pneumonia are eligible. Patients must be at least 3 weeks from prior thoracotomy if performed.

Exclusion Criteria: N3 supraclavicular disease; Greater than minimal, exudative, or cytologically positive pleural effusions; Involved contralateral hilar nodes i. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; Prior therapy that specifically and directly targets the epidermal growth factor receptor EGFR pathway; Prior severe infusion reaction to a monoclonal antibody; Severe, active co-morbidity, defined as follows: Significant history of uncontrolled cardiac disease; i.

The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients. Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin; Uncontrolled neuropathy grade 2 or greater regardless of cause. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.