To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials.
One male pelvis computed tomography (CT) data set and one female pelvis CT data ...set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified.
The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed.
Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.
The role of adjuvant radiation in uterine sarcomas Sampath, Sagus; Schultheiss, Timothy E; Ryu, Janice K ...
International journal of radiation oncology, biology, physics,
03/2010, Letnik:
76, Številka:
3
Journal Article
Recenzirano
To determine clinical and pathological factors significant for overall survival (OS) and local-regional failure-free survival (LRFFS) in uterine sarcoma as they relate to adjuvant radiotherapy (AR).
...A retrospective analysis of 3,650 patients with uterine sarcoma was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by Impac Medical Systems (Sunnyvale, CA). Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis, with or without brachytherapy. Prognostic factors were identified by multivariate analysis (MVA) using the Cox proportional hazards model. The Kaplan-Meier method was used to estimate survival, with significant differences (p < 0.05) determined using the log-rank test.
The median follow-up time was 59 months, with a 5-year OS of 37%. Significant prognostic factors for OS were stage, race/ethnicity, grade, age, histology, lymph node status, and surgical treatment (p < 0.01 for all factors). Use of AR was not predictive for OS. For nonmetastatic cancer patients receiving definitive surgery (n = 2,206), the 5-year LRFFS was 87%. In this group, stage, grade, histology, and AR were prognostic for LRFFS (p < 0.05), with AR associated with improved outcome compared with surgery alone (hazard ratio = 0.4, p < 0.001). Patients with carcinosarcoma, endometrial stromal sarcoma, leiomyosarcoma, poorly differentiated tumors, and negative lymph nodes had reduced local-regional failure (LRF) with AR (log-rank, p < 0.05 for all).
In the largest retrospective analysis of uterine sarcoma published thus far, AR conferred a 53% reduction in the risk of LRF at 5 years. Use of AR may have broader indications than what are currently accepted in clinical practice.
To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer.
A total of 179 ...patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation dose levels depending on the percentage of the total lung volume that received >20 Gy with the treatment plan (V(20)). Patients with a V(20) <25% (Group 1) received 70.9 Gy in 33 fractions, 77.4 Gy in 36 fractions, 83.8 Gy in 39 fractions, and 90.3 Gy in 42 fractions, successively. Patients with a V(20) of 25-36% (Group 2) received doses of 70.9 Gy and 77.4 Gy, successively. The treatment arm for patients with a V(20) > or =37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days after the start of radiotherapy were scored as late toxicities. The estimated toxicity rates were calculated on the basis of the cumulative incidence method.
The following acute Grade 3 or worse toxicities were observed for Group 1: 70.9 Gy (1 case of weight loss), 77.4 Gy (nausea and hematologic toxicity in 1 case each), 83.8 Gy (1 case of hematologic toxicity), and 90.3 Gy (3 cases of lung toxicity). The following acute Grade 3 or worse toxicities were observed for Group 2: none at 70.9 Gy and 2 cases of lung toxicity at 77.4 Gy. No patients developed acute Grade 3 or worse esophageal toxicity. The estimated rate of Grade 3 or worse late lung toxicity at 18 months was 7%, 16%, 0%, and 13% for Group 1 patients receiving 70.9, 77.4, 83.8, or 90.3 Gy, respectively. Group 2 patients had an estimated late lung toxicity rate of 15% at 18 months for both 70.9 and 77.4 Gy. The prognostic factors for late pneumonitis in multivariate analysis were the mean lung dose and V(20). The estimated rate of late Grade 3 or worse esophageal toxicity at 18 months was 8%, 0%, 4%, and 6%, for Group 1 patients receiving 70.9, 77.4, 83.8, 90.3 Gy, respectively, and 0% and 5%, respectively, for Group 2 patients receiving 70.9 and 77.4 Gy. The dyspnea index scoring at baseline and after therapy for functional impairment, magnitude of task, and magnitude of effort revealed no change in 63%, functional pulmonary loss in 23%, and pulmonary improvement in 14% of patients. The observed locoregional control and overall survival rates were each similar among the study arms within each dose level of Groups 1 and 2. Locoregional control was achieved in 50-78% of patients. Thirty-one patients developed regional nodal failure. The location of nodal failure in relationship to the RT volume was documented in 28 of these 31 patients. Twelve patients had isolated elective nodal failures. Fourteen patients had regional failure in irradiated nodal volumes. Two patients had both elective nodal and irradiated nodal failure.
The radiation dose was safely escalated using three-dimensional conformal techniques to 83.8 Gy for patients with V(20) values of <25% (Group 1) and to 77.4 Gy for patients with V(20) values between 25% and 36% (Group 2), using fraction sizes of 2.15 Gy. The 90.3-Gy dose level was too toxic, resulting in dose-related deaths in 2 patients. Elective nodal failure occurred in <10% of patients.
To update the incidence of late toxicity of RTOG 9406, a three-dimensional conformal radiation therapy (3DCRT) dose escalation trial for prostate cancer.
A total of 1,084 men were registered to this ...Phase I/II trial of 3DCRT (eligible patients, 1,055). The dose for level I was 68.4 Gy; 73.8 Gy for level II; 79.2 Gy for level III; 74 Gy for level IV; and 78 Gy for level V. Patients in levels I to III received 1.8 Gy/fraction, and those in levels IV to V received 2.0 Gy/fraction. Disease group I patients were treated at the prostate only, group 2 patients were treated at the prostate and at the seminal vesicles with a prostate boost, and group 3 patients were treated at the prostate and seminal vesicles. The median follow-up period for surviving patients was 6.1 y (level V) to 12.1 y (level I).
The incidence rates of RTOG grade 3 or less gastrointestinal or genitourinary toxicity were 3%, 4%, 6%, 7%, and 9% in group 1 and 6%, 2%, 6%, 9%, and 12% in group 2 at dose levels of I, II, III, IV, and V, respectively. In group 1, level V patients had a higher probability of grade 2 late or greater gastrointestinal or genitourinary toxicity than those in levels I, II, and III (hazard ratio HR = 1.93, p = 0.0101; HR = 2.29, p = 0.0007; HR = 2.52, p = 0.0002, respectively). In group 2, dose level V patients had a higher probability of grade 2 or greater late gastrointestinal or genitourinary toxicity than those in dose levels II, III, and IV (HR = 2.61, p = 0.0002; HR = 2.22, p = 0.0051; HR = 1.60, p = 0.0276, respectively).
Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to 79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.
Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, ...placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients.
Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 microg/m2 or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system.
Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006).
This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.
Purpose
: A prospective Phase I dose escalation study was conducted to determine the maximally tolerated radiation dose in men treated with three-dimensional conformal radiotherapy (3D-CRT) for ...localized prostate cancer. This is a preliminary report of toxicity at Level III (79.2 Gy) on 3D Oncology Group/Radiation Therapy Oncology Group (RTOG) 9406.
Methods and Materials
: Between November 26, 1996 and October 1, 1998, 173 patients with clinically organ-confined prostate cancer (T1 and T2) were accrued to a Level III dose of 79.2 Gy. One hundred sixty-nine patients were available for analysis of toxicity. Patients were registered to two groups according to the risk of seminal vesicle invasion (SVI) on the basis of presenting PSA and Gleason score. Group 1 patients had a calculated risk of SVI <15%, and Group 2 patients had a risk of SVI ≥15%. For Group 1 patients, the planning target volume (PTV) margins were 5–10 mm around the prostate only. For Group 2 patients, the same margins were applied to the prostate and seminal vesicles (PTV
1) for the initial 55.8 Gy; then treatment volume was reduced to the prostate only (PTV
2). To reduce the rectal dose on dose Level III, the minimum PTV dose was limited to 73.8 Gy, whereas the minimum gross target volume dose was 79.2 Gy, both in 44 fractions. The incidence of ≥3 Grade late effects was compared to that in a similar group of patients treated on RTOG 7506 and 7706 studies.
Results
: Acute tolerance to 79.2 Gy was excellent with no patients experiencing ≥ Grade 3 acute toxicity. The acute toxicity rate was comparable to that reported for previous lower dose levels. With the median follow-up of 3.3 years (range: 0.4–4.4 years), a total of 4 patients (2.4%) experienced Grade 3 late toxicity, three cases of which were related to the bladder, and one related to the rectum. There were no Grade 4 or 5 late complications noted during the period of observation. These results are also comparable to those reported at dose Levels I and II. The expected incidence of ≥3 Grade 3 late toxicity was calculated using historical data from two previous RTOG prostate cancer trials, 7506 and 7706. The calculated risk accounted for the difference in follow-up duration between patients in this study and the historical experience. The observed rate of ≥ Grade 3 late effects for Group 1 (two cases) is significantly lower (
p = 0.0002) than the 17.6 cases that would have been expected from the historical control. The observed rate for Group 2 (two cases) was also significantly lower (
p = 0.0037) than the 12.1 cases expected.
Conclusion
: Based on excellent tolerance of 3D-CRT for stages T1 and T2 prostate cancer, further biological dose escalation has been pursued to Levels IV and V, 74 Gy and 78 Gy, respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. This trial has closed. A Phase III comparative RTOG trial is being developed to determine whether high-dose 3D-CRT improves efficacy.
This multicentered phase III trial was designed to compare an emulsion containing trolamine against the usual supportive care within each participating institution for patients with head and neck ...cancer undergoing radiation therapy.
Patients with biopsy-proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to one of the following treatments: prophylactic trolamine emulsion, interventional trolamine emulsion, or declared institutional preference. The primary outcome was the reduction in grade 2 or higher skin toxicity, as per National Cancer Institute Common Toxicity Criteria version 2.0. Secondary outcomes included patient-reported quality of life (QOL).
From October 2000 to April 2002, 547 patients from 51 institutions were entered onto the trial. The average age was 59 years. Patients were predominately male (79%) and most continued to use tobacco products (52%). The rates of grade 2 or higher radiation dermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms of the study, respectively. No significant differences in QOL were found.
The results of this trial demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiation dermatitis or improving patient-reported QOL. The use of 15 different local standards of care highlights the need to continue research that will result in evidence-based recommendations to reduce the burden of radiation dermatitis.
This study aimed to measure expression of cyclooxygenase-2 (COX-2) and CD34 in pretreatment tumor biopsies from patients on the RTOG C0128 phase II study, and to correlate expression of these ...biomarkers, using quantitative immunohistochemistry, with clinical outcome parameters.
Pretreatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative immunohistochemistry (AQUA®). Cox regression models and Fisher's exact test were used to explore associations between expression of the biomarkers and clinical end points.
Eighty-four patients were accrued between 2001 and 2004; 78 were eligible and analyzable. Pathology specimen submission was optional; COX-2 expression was determined for 37 (47%) of patients, and CD34 scoring was determined for 34 (44%) of patients. Median follow-up was 44.5 months. In tumors where COX-2 data were available, 6 (16%) of 37 patients had local-regional failure; 4 of these patients had tumors with COX-2 scores below the AQUA® score median (hazard ratio, 0.39; 95% confidence interval, 0.07-2.16; P = 0.28). Of the 8 patients with disease-free survival failures, 5 had tumors with COX-2 levels below the median (hazard ratio, 0.49; 95% confidence interval, 0.12-2.04; P = 0.32). The 4 patients who died all had COX-2 levels below the median value. COX-2 levels below the median were associated with worse 2-year survival (Fisher's P = 0.046). There was no statistically significant association between CD34 status and clinical outcome.
Low COX-2 expression measured by AQUA® was associated with worse overall survival in this subset of patients available for analysis from RTOG C0128. Application of AQUA® technology, in a larger study, will be required to definitively evaluate the association COX-2 with clinical outcome in cervical cancer.
To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy.
...Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size > or =5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity.
Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%.
Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.
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