scholarly journals Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin

2012 ◽  
Vol 30 (35) ◽  
pp. 4344-4351 ◽  
Author(s):  
Leonard L. Gunderson ◽  
Kathryn A. Winter ◽  
Jaffer A. Ajani ◽  
John E. Pedersen ◽  
Jennifer Moughan ◽  
...  
Keyword(s):  
Anal Canal ◽  
Radiation Therapy Oncology Group ◽  
Anal Carcinoma ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Concurrent Chemoradiation ◽  
Tumor Diameter ◽  
Free Survival ◽  
Node Status

Purpose On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group. Patients and Methods Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors. Results Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS. Conclusion CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.

Intergroup RTOG 98–11: A phase III randomized study of 5-fluorouracil (5-FU), mitomycin, and radiotherapy versus 5-fluorouracil, cisplatin and radiotherapy in carcinoma of the anal canal

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4009-4009 ◽  
Author(s):  
J. A. Ajani ◽  
K. A. Winter ◽  
L. L. Gunderson ◽  
J. Pedersen ◽  
A. B. Benson ◽  
...  
Keyword(s):  
Statistical Power ◽  
Randomized Study ◽  
Anal Carcinoma ◽  
Disease Free Survival ◽  
Patient Characteristics ◽  
Phase Iii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

4009 Background: An ∼65% 5-year disease-free-survival (DFS) rate from 5-FU/mitomycin/radiation for anal carcinoma needs improvement. Methods: A phase III randomized trial compared 5-FU (1,000mg/m2 days 1–4 and 29–32) plus mitomycin (10mg/m2 days 1 and 29) and radiation (45 to 59 Gy) (Arm A) to 5-FU (1,000mg/m2 days 1–4, 29–32, 57–60 and 85–88) plus cisplatin (75mg/m2 on days 1, 29, 57 and 85) and radiation (45 to 59 Gy; start day=57) (Arm B) in anal carcinoma patients. Stratification included gender, clinical N status and tumor diameter. Primary endpoint was DFS. Statistical power was 80% with two-sided test to detect 10% DFS increase for Arm B. Results: Of 682 patients accrued, 598 were analyzable. Most unanalyzed patients’ data are early. Patient characteristics were balanced. Median age was 55 years, women predominated (69%), 27.5% had >5 cm tumor diameter and 26% had clinically N+ cancer. Preliminary 5-year estimated DFS was 56% for Arm A and 48% for Arm B (p=0.28) and 5-year estimated overall survival was 69% for both arms (p=0.24). Men(p=0.04), clinically N+ cancer (p<0.0001) and tumor diameter >5 cm (p=0.005) independently prognosticated DFS in a multivariate analysis. 5-year colostomy rate was 10% for Arm A and 20% for arm B(p=0.12). Grade 3/4 toxicity rates: non-hematologic=76% for Arm A and 75% for Arm B but hematologic=67% for Arm A and 47% for Arm B(p=0.0004). Conclusions: In Intergroup-98–11, induction 5-FU/cisplatin followed by 5-FU/cisplatin/radiation failed to improve DFS compared to the standard treatment, 5-FU/mitomycin/radiation. Supported by RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115. No significant financial relationships to disclose.

Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31.

1997 ◽  
Vol 15 (3) ◽  
pp. 1013-1021 ◽  
Author(s):  
M V Pilepich ◽  
R Caplan ◽  
R W Byhardt ◽  
C A Lawton ◽  
M J Gallagher ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Radiation Therapy Oncology Group ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Oncology Group ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Carcinoma Of The Prostate ◽  
Androgen Suppression ◽  
Disease Free

PURPOSE Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. MATERIALS AND METHODS In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. RESULTS Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). CONCLUSION Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

Long-term update of U.S. GI Intergroup RTOG 98-11 phase III trial for anal carcinoma: Comparison of concurrent chemoradiation with 5FU-mitomycin versus 5FU-cisplatin for disease-free and overall survival.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 367-367 ◽  
Author(s):  
L. L. Gunderson ◽  
K. A. Winter ◽  
J. A. Ajani ◽  
J. E. Pedersen ◽  
A. B. Benson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Statistical Significance ◽  
Anal Carcinoma ◽  
Phase Iii ◽  
Concurrent Chemoradiation ◽  
Rank Test ◽  
Test Time ◽  
Treatment Intensification ◽  
Disease Free

367 Background: On initial publication of GI Intergroup RTOG 98-11, concurrent chemoradiation with 5FU+mitomycin (MMC) decreased colostomy failure (CF) vs induction plus concurrent 5FU+cisplatin (CDDP), but did not significantly impact disease free or overall survival (DFS, OS). The intent of the current analysis is to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free [CFS]), CF and relapse (local-regional [LRF], distant [DM]) in this patient group. Methods: Stratification factors included gender, clinical node status, and primary size. DFS/OS were estimated univariately by Kaplan-Meier method and treatment arms compared by log-rank test. Time to relapse/CF were estimated by cumulative incidence method and treatment arms compared by Gray's test. Multivariate analyses were done with Cox proportional hazard models to test for treatment differences, adjusting for stratification factors. Results: Of 682 patients accrued, 649 were analyzable for outcomes. As seen in the table, 5-yr DFS and OS were statistically better for RT+5FU/MMC vs RT+5FU/CDDP (67.7 v 57.6%, p=.0.0045; 78.2 v 70.5%, p=0.021) with trends toward statistical significance for CFS, LRF, and CF (71.8 v 64.9%, p=0.053; 20 v 26.5%, 11.9 v 17.3%, p=0.092 and 0.075). Similar results were seen in multivariate analysis. Conclusions: Concurrent chemoradiation with 5FU-MMC has a statistically significant impact on DFS and OS vs induction + concurrent 5FU-CDDP and borderline significance for CFS, CF and LRF. Therefore, RT+5FU/MMC remains the preferred standard of care. Potential strategies to improve outcomes include treatment intensification and individualized molecular-based treatment. Supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). [Table: see text] No significant financial relationships to disclose.

Cisplatin (C) based chemoradiation (CXRT) for locally advanced squamous cell carcinoma (SCCA) of the anal canal (AC): A 20-year perspective.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 482-482 ◽  
Author(s):  
C. Eng ◽  
Y. Xing ◽  
Y. N. You ◽  
G. J. Chang ◽  
P. Das ◽  
...  
Keyword(s):  
Anal Canal ◽  
Salvage Surgery ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Free Survival ◽  
Phase Iii Studies

482 Background: The standard of care for locally advanced SCCA of the AC is 5-fluorouracil (5-FU)/mitomycin C (MMC) with concurrent XRT. C was evaluated with 5-FU in 2 large phase III studies (RTOG 98-11 and ACT II) to establish superiority over 5-FU/MMC. Neither study showed significant differences for disease-free survival (DFS) or overall survival (OS). RTOG 98-11 reported reduced colostomy-free survival (CFS) in the C-induction arm; no differences were noted in the ACT II study. We present our 20-year experience with C for locally advanced SCCA of the AC which has been adopted as the standard unless contraindicated. Methods: A retrospective, single institution analysis for locally advanced SCCA of the AC was completed in patients (pts) that received concurrent 5-FU/C/XRT from 1989-2009. Medical records were reviewed for history of STDs, chronic immunosuppression, stage, dose of XRT, toxicity, clinical response (CR), recurrence, and OS. Multidisciplinary management included surgical, radiation, and medical oncologists. OS, DFS, and CFS were calculated using the K-M method. The log-rank test was used to compare OS among these subgroups. Results: 185 pts were identified (51 M:134 F). The median age was 56 (35-83 y.o.). AJCC stage was I (n = 25); II (n = 76); IIIA (n = 36); and IIIB (n = 48). The median XRT dose was 55 Gy in 30 fractions. 181 pts were evaluable for response; 4 were lost to follow up. Complete CR (cCR) was noted in 169 pts (93%); partial response (n = 12); 6 pts received an APR. After a median follow up of 8.6 years, 14 pts (8%) developed local recurrence; 11 received salvage surgery. 16 pts (9%) developed distant metastases (DM). The 5-yr DFS = 81%, 5-yr OS = 85% and 5-yr CFS was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-yr DFS (p = 0.02) and DM (p = 0.046) but not OS or CFS. Increased T-stage correlated with salvage surgery (p = 0.005). Conclusions: Cisplatin-based chemoradiation for locally advanced SCCA of the anal canal resulted in favorable DFS, OS, and CFS compared to historical data and phase III studies. Platinum-based therapy for anal cancer appears to be an acceptable alternative to MMC and should be considered as a standard option for locally advanced disease. No significant financial relationships to disclose.

scholarly journals US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

2009 ◽  
Vol 27 (7) ◽  
pp. 1116-1121 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Kathryn A. Winter ◽  
Leonard L. Gunderson ◽  
John Pedersen ◽  
Al B. Benson ◽  
...  
Keyword(s):  
Radiation Therapy Oncology Group ◽  
Anal Carcinoma ◽  
Secondary Analysis ◽  
Disease Free Survival ◽  
Nodal Status ◽  
Tumor Diameter ◽  
Prognostic Variables ◽  
Large Tumor ◽  
The Us ◽  
Large Tumor Diameter

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma.

The impact of the duration of adjuvant hormonal therapy in patients with unfavorable prognosis prostate cancer treated with radiotherapy: Secondary analysis of RTOG 85–31

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5062-5062 ◽  
Author(s):  
L. Souhami ◽  
K. Bae ◽  
M. V. Pilepich ◽  
H. Sandler
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Adjuvant Hormonal Therapy ◽  
End Points ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

5062 Background: RTOG 85–31 was a Phase III trial of androgen suppression for life as an adjuvant to radiotherapy. However not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrent disease. This analysis correlates duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued long-term hormonal therapy. Methods: The protocol mandated pelvic radiotherapy (60–66 Gy) followed by goserelin 3.6 mg monthly given indefinitely or until disease progression. To avoid potential bias due to early progression/death, only patients who were alive with no evidence of disease at the time of cessation of hormonal therapy were included. There were 377 analyzable patients. Patients were divided in groups based on the hormonal therapy duration (HTD), as follows: = 1 year (27.3%), 1< and =2 years (11.4%), 2< and =4 years (13.3%), 4< and =6 years (10.6%) and > 6 years (37.4%). End-points were overall survival, disease-free survival, disease-free survival with PSA <1.5 ng/mL, disease-specific survival, local failure and distant failure. Cox-proportional hazards regression model was used to test the outcomes among the 5 groups. Results: The median follow-up time of surviving patients is 11.27 years. Pretreatment characteristics by hormone duration groups were well balanced except for age. The median duration of adjuvant hormonal therapy was 3.59 years. For each outcome, there are statistically significant differences among the 5 HTD groups in all outcomes without adjusting for other covariates. Pairwise comparisons show that HTD > 6 year group is significantly associated with having an improved survival and fewer failure events than all other HTD groups (HR < 1, p-value <0.0001). Adjusted for age and stratification variables, the HTD>6 year group remains the only group significantly associated with having fewer failure events in all outcomes. Conclusions: Prolonged HTD of > 6 years is significantly associated with improvements in all end-points studied. Based on these data, decreasing HTD to < 6 years may have a detrimental effect in patients with unfavorable prostate cancer. No significant financial relationships to disclose.

scholarly journals Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis

2021 ◽  
Vol 39 (2) ◽  
pp. 136-144
Author(s):  
Daniel E. Spratt ◽  
Shawn Malone ◽  
Soumyajit Roy ◽  
Scott Grimes ◽  
Libni Eapen ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Meta Analysis ◽  
Radiation Therapy Oncology Group ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Oncology Group ◽  
Short Term ◽  
Free Survival

PURPOSE There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa. METHODS MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS). RESULTS The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups. CONCLUSION The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.

1461: Local Control and Long Term Disease Free Survival Following Radical Prostatectomy for D1 Prostate Cancer In The PSA ERA

2004 ◽  
Vol 171 (4S) ◽  
pp. 385-385 ◽  
Author(s):  
Carl K. Gjertson ◽  
Kevin P. Asher ◽  
Joshua D. Sclar ◽  
Aaron E. Katz ◽  
Erik T. Goluboff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Local Control ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study.

1991 ◽  
Vol 9 (4) ◽  
pp. 581-591 ◽  
Author(s):  
A T Look ◽  
F A Hayes ◽  
J J Shuster ◽  
E C Douglass ◽  
R P Castleberry ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Gene Amplification ◽  
Gene Copy Number ◽  
Disease Free Survival ◽  
Gene Copy ◽  
Early Treatment Failure ◽  
Free Survival ◽  
Myc Gene ◽  
Disease Free

We assessed tumor cell DNA content (ploidy) and N-myc gene copy number as predictors of long-term disease-free survival in 298 children with neuroblastoma. Diploid tumor stem lines were identified in 101 patients (34%), clonal hyperdiploid abnormalities in 194 (65%), and hypodiploid stem lines in three (1%). In children with widely disseminated tumors at diagnosis (stage D), ploidy had a highly age-dependent influence on prognosis. Among infants (less than 12 months) treated with cyclophosphamide-doxorubicin, hyperdiploidy was closely associated with long-term disease-free survival (greater than 90% of cases), while diploidy invariably predicted early treatment failure (P less than .001). Similarly, in children 12 to 24 months of age who were treated with cisplatin-teniposide and cyclophosphamide-doxorubicin, diploidy uniformly predicted early failure, whereas half of the children with hyperdiploidy achieved long-term disease-free survival (P less than .001). There was no relationship between ploidy and treatment outcome in children older than 24 months with stage D tumors who had a very low probability of long-term disease-free survival (less than 10%). N-myc gene amplification was detected in 37 (25%) of the 147 tumors tested, with the remainder showing single-copy levels of the gene. N-myc gene amplification was more frequent in diploid than in hyperdiploid tumors (23 of 57 v 14 of 87, P = .001) and predicted a high likelihood of early treatment failure. In children younger than 2 years with disseminated neuroblastoma, tumor cell ploidy and N-myc gene copy number provide complementary prognostic information that will distinguish patients who can be cured on current regimens from those who require new treatment strategies.

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