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Title: Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129

Abstract

Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292more » of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.« less

Authors:
 [1];  [2];  [3];  [4];  [3];  [5];  [6];  [7];  [1];  [8];  [9]
  1. Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)
  2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States)
  3. Centre Hospitalier de l'Universite de Montreal-Notre Dame, Montréal, Québec (Canada)
  4. University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  5. L Hotel-Dieu de Quebec, Québec City, Québec (Canada)
  6. The James Brown Cancer Center–University of Louisville, Louisville, Kentucky (United States)
  7. University of California Davis Medical Center, Sacramento, California (United States)
  8. London Regional Cancer Program, London, Ontario (Canada)
  9. Stanford University Medical Center, Stanford, California (United States)
Publication Date:
OSTI Identifier:
22645653
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; MULTIVARIATE ANALYSIS; NECK; NEOPLASMS; PATIENTS

Citation Formats

Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu, Zhang, Qiang, Nguyen-Tan, Phuc Felix, Rosenthal, David I., Soulieres, Denis, Fortin, André, Silverman, Craig L., Daly, Megan E., Ridge, John A., Hammond, J. Alexander, and Le, Quynh-Thu. Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.05.026.
Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu, Zhang, Qiang, Nguyen-Tan, Phuc Felix, Rosenthal, David I., Soulieres, Denis, Fortin, André, Silverman, Craig L., Daly, Megan E., Ridge, John A., Hammond, J. Alexander, & Le, Quynh-Thu. Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129. United States. doi:10.1016/J.IJROBP.2016.05.026.
Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu, Zhang, Qiang, Nguyen-Tan, Phuc Felix, Rosenthal, David I., Soulieres, Denis, Fortin, André, Silverman, Craig L., Daly, Megan E., Ridge, John A., Hammond, J. Alexander, and Le, Quynh-Thu. 2016. "Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129". United States. doi:10.1016/J.IJROBP.2016.05.026.
@article{osti_22645653,
title = {Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129},
author = {Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu and Zhang, Qiang and Nguyen-Tan, Phuc Felix and Rosenthal, David I. and Soulieres, Denis and Fortin, André and Silverman, Craig L. and Daly, Megan E. and Ridge, John A. and Hammond, J. Alexander and Le, Quynh-Thu},
abstractNote = {Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.},
doi = {10.1016/J.IJROBP.2016.05.026},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 96,
place = {United States},
year = 2016,
month =
}
  • Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less
  • Purpose: In the literature, a favorable prognosis was observed for complete pathologic response after preoperative therapy (ypCR) in patients with locally advanced rectal cancer. The aim of this study is to verify whether ypCR predicts a favorable outcome in a large series of patients. Methods and Materials: The Gastro-Intestinal Working Group of the Italian Association of Radiation Oncology collected clinical data for 566 patients with ypCR (ypT0N0) after neoadjuvant therapy. Eligibility criteria included locally advanced rectal cancer with no evidence of metastases at the time of diagnosis, evidence of ypCR after preoperative radiotherapy {+-} chemotherapy (CT). Results: Median radiation dosemore » was 50 Gy. A total of 527 patients (93%) received one of 12 different neoadjuvant CT schedules. Sphincter preservation, anteroposterior resection, and endoscopic surgery were performed in 73%, 22%, and 5% of patients, respectively. Adjuvant CT was administered to 22% of patients. Median follow-up was 46.4 months. Locoregional recurrence occurred in 7 patients (1.6%). Distant metastases occurred in 49 patients (8.9%). Overall, 5-year rates of disease-free survival, overall survival, and cancer-specific survival were 85%, 90%, and 94%, respectively. In multivariate analysis, only age and clinical stage statistically correlated with survival outcome. Adjuvant CT was still of borderline significance (worse for adjuvant CT). No relation was found between survival and neoadjuvant CT schedules. Conclusion: A ypCR after neoadjuvant therapy identified a favorable group of patients, even in this large series of 566 patients collected in 61 centers. Locoregional recurrence occurred only in 1.6% patients.« less
  • Purpose: To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy). Patients and Methods: A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose ofmore » at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among the 119 eligible patients, 101 (85%) achieved T0, and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36 of 101 T0 patients (36%) versus 5 of 18 Ta or Tis patients (28%) experienced bladder recurrence (P=.52). Thirteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, compared with 1 patient among near-complete responders (P=.63). Disease-specific, bladder-intact, and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: The bladder recurrence and salvage cystectomy rates of the complete and the near-complete responders were similar. Therefore it is reasonable to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy with consolidation chemo-RT to full dose (60-64 Gy).« less
  • Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined,more » multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.« less
  • Purpose: To determine whether overall treatment time affects outcomes after definitive concurrent chemoradiotherapy for locally advanced non-small-cell lung carcinoma (NSCLC). Methods and Materials: Data were analyzed from 3 prospective Radiation Therapy Oncology Group trials (RTOG 91-06, 92-04, and 94-10) in which immediate concurrent chemoradiation (cisplatin-based) was the primary therapy for good-performance status Stage III (and selected inoperable Stage II) NSCLC. 'Short' overall treatment time (per protocol) was defined as completing treatment within 5 days of plan; other patients were considered to have had 'prolonged' treatment time (protocol violation); treatment time was also analyzed as a continuous variable in a multivariatemore » model. Actuarial analysis was performed for overall survival, progression-free survival, freedom from local-regional progression, and toxicity. Results: A total of 474 patients were analyzed. Median follow-up for surviving patients was 6.1 years. Treatment time was delivered per protocol in 387 (82%), whereas 87 patients (18%) had a prolonged treatment time. Long treatment time was significantly associated with severe acute esophagitis. Median survival was slightly better in patients completing treatment on time (19.5 months vs. 14.8 months), but this did not reach statistical significance (p = 0.15) in the univariate analysis. However, in the multivariate analysis of treatment time as a continuous variable, prolonged treatment time was significantly associated with poorer survival (p = 0.02), indicating a 2% increase in the risk of death for each day of prolongation in therapy. Histology (squamous fared worse) and performance status were also significant in the multivariate model. Conclusions: This retrospective analysis demonstrates a correlation between prolonged overall radiotherapy treatment time and survival in patients with locally advanced NSCLC, even when concurrent chemotherapy is used. Further study of novel radiation-chemotherapy dose/fractionation regimens is warranted.« less