Radiation Therapy Oncology Group Score Research Articles

Colorectal complications of external beam radiation versus brachytherapy for prostate cancer

Background Although radiation therapy plays a central role in the management of prostate cancer, complications remain a troubling byproduct. We sought to determine the prevalence and significance of colorectal complications after external beam radiation (EBRT) versus brachytherapy (BT) for prostate cancer. Methods We performed a retrospective review of all patients undergoing EBRT or BT for prostate cancer from January 1999 to October 2005. Toxicities were graded using the Radiation Therapy Oncology Group scoring system or the modified Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading criteria. Results A total of 183 patients underwent EBRT and 50 patients underwent BT with a mean follow-up period of 39 months. BT was associated with significantly less acute (6% vs 43.5%) and late toxicities (2% vs 21.8%; both P < .001). Among patients receiving EBRT, acute grade 3 toxicity was experienced by 1 (.5%) patient, and grade 2 toxicity was experienced by 79 (43%) patients. Increased stool frequency was the most common manifestation (62%), followed by rectal pain and urgency (30%) and rectal bleeding (21%). Late toxicity included 34 (18.6%) patients with grade 2 toxicity (bleeding, 68%; frequent stools, 26%; pain and urgency, 18%), and 5 patients (2.7%) with grade 3 toxicity (bleeding requiring multiple cauterizations, 3; small-bowel obstruction requiring surgery, 1; anal stenosis requiring repeat dilations, 1). BT was relatively well tolerated, with only 3 patients (6%) experiencing grade 2 acute toxicity symptoms of pain and urgency. One BT patient suffered late grade 2 toxicity of bleeding requiring intervention. One patient developed rectal cancer 20 years after EBRT. Conclusions Despite its relative safety, radiation therapy for prostate cancer has a significant incidence of colorectal complications. Overall, BT has a significantly lower incidence of acute and late toxicities than EBRT.

Image-guided helical Tomotherapy for treatment of spine tumors

Objectives One of the most common indications for radiotherapy is treatment of the spine. The vast majority of cases are related to metastatic disease with primary tumors of the spine being rare. Conventional radiation therapy often plays an important role in the management of spine tumors although at times with significant side effects and disadvantages. Furthermore, retreatment of spine tumors is a challenge due to concerns over spinal cord toxicity. In this series, we examine the efficacy of using image-guided helical Tomotherapy and the possible advantages offered by this new technology. Patients and methods Eight patients at Hoag Memorial Hospital Presbyterian were treated between November 2005 and November 2006. The median age was 66 years. Of the eight patients, seven had metastatic disease with one patient having a primary neuroendocrine tumor of the spine. Five patients were previously treated to the spine with conventional radiation planning. Two patients received single fraction stereotactic radiosurgery (15 Gy) while the remaining patients received hypofractionated stereotactic radiotherapy to a median total dose of 2500 cGy in 500 cGy fractions. Results At the time of last follow-up, radiographic control was seen in all eight patients with a median local control rate of 2.5 months (range of 1–5.8 months). Four of the eight patients are still alive with median overall survival of 5.1 months (range 1.4–6.9 months). Acute toxicity ranged from Radiation Therapy Oncology Group (RTOG) score 0–2 and no patients experienced late complications of radiation myelitis. Conclusions The TomoTherapy Hi-ART system can be an alternative treatment option for upfront or retreatment of spine tumors. Minimal acute and late toxicity were seen in patients treated with Tomotherapy. Intensity-modulated radiation delivery combined with megavoltage CT image guidance offered by the TomoTherapy Hi-ART system allows for set-up and delivery accuracy that is required for stereotactic treatment of spine tumors and eliminates the need for any internal or external fiducial marker placement.

Intensity-Modulated Radiotherapy of Pelvic Lymph Nodes in Locally Advanced Prostate Cancer: Planning Procedures and Early Experiences

We present planning and early clinical outcomes of a study of intensity-modulated radiotherapy (IMRT) for locally advanced prostate cancer. A total of 43 patients initially treated with an IMRT plan delivering 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes, followed by a conformal radiotherapy (CRT) plan delivering 20 Gy to the prostate and seminal vesicles, were studied. Dose-volume histogram (DVH) data for the added plans were compared with dose-volume histogram data for the sum of two CRT plans for 15 cases. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the Radiation Therapy Oncology Group scoring system, was recorded weekly throughout treatment as well as 3 to 18 months after treatment and are presented. Treatment with IMRT both reduced normal tissue doses and increased the minimum target doses. Intestine volumes receiving more than 40 and 50 Gy were significantly reduced (e.g., at 50 Gy, from 81 to 19 cm(3); p = 0.026), as were bladder volumes above 40, 50, and 60 Gy, rectum volumes above 30, 50, and 60 Gy, and hip joint muscle volumes above 20, 30, and 40 Gy. During treatment, Grade 2 GI toxicity was reported by 12 of 43 patients (28%), and Grade 2 to 4 GU toxicity was also observed among 12 patients (28%). With 6 to 18 months of follow-up, 2 patients (5%) experienced Grade 2 GI effects and 7 patients (16%) experienced Grade 2 GU effects. Use of IMRT for pelvic irradiation in prostate cancer reduces normal tissue doses, improves target coverage, and has a promising toxicity profile.

Radical radiotherapy with high‐dose‐rate brachytherapy for uterine cervix cancer long‐term results†

The aim of this is to report the results of radical radiotherapy in carcinoma of the cervix treated by high-dose rate (HDR) intracavitary brachytherapy and external beam radiotherapy (XRT) at a single centre in Singapore. This is a retrospective analysis of 106 consecutive cases with histologically proven cervical cancer, treated by HDR brachytherapy and XRT at the Mount Elizabeth Hospital from 1990 to 1993. External beam radiotherapy to the pelvis was delivered with 6 MV photons, to 45-50.4 Gy in 1.8 Gy fractions. High-dose-rate brachytherapy comprised two to three applications of an intrauterine tandem with paired ovoids, to a median dose of 18 Gy to point 'A', carried out during XRT. All 106 patients completed treatment. Their ages ranged from 32 to 80 years (median 57 years). Most patients presented with stage II or III disease (44 and 37%, respectively) and with squamous cell carcinoma (91%). Median follow-up time was 59 months (range 2-169 months). The 5-year relapse-free survival rate across all stages was 71%. The corresponding overall survival rate was 69%. Local control was achieved in 86 patients (81%); six patients had residual disease (6%), and 14 patients had local recurrence (13%). Fourteen patients developed metastatic disease (13%). On univariate analysis, tumour stage, haemoglobin level, number of brachytherapy treatments and overall treatment time were found to be prognostic factors for overall survival. Late complications were mild (Radiation Therapy Oncology Group score 1-2), except for one patient with grade 4 rectal toxicity. The complication rates were 8, 14 and 45%, respectively, for the rectum, bladder and vagina (stenosis). The use of two to three fractions of HDR intracavitary brachytherapy in addition to pelvic XRT achieves good outcomes.

Proctitis after external-beam radiotherapy for prostate cancer classified by Vienna Rectoscopy Score and correlated with EORTC/RTOG score for late rectal toxicity: Results of a prospective multicenter study of 166 patients

To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity. A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT. Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS. Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01). The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.

A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p = 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p = 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.

Comparing measures of acute bowel toxicity in patients with prostate cancer treated with external beam radiation therapy

This study strives to compare early measures of bowel toxicity in patients with prostate cancer receiving definitive or adjuvant 3D conformal external beam radiation therapy and concurrent daily endorectal application of amifostine. Eighteen patients were enrolled in the clinical study with a median follow-up of 12 months. Prescription doses ranged from 66 Gy to 76 Gy with a daily fractionation of 2 Gy. Acute bowel toxicity was measured at baseline, at Weeks 5 and 7 of radiotherapy, and at 1 and 3 months after the completion of therapy. Measures of acute bowel toxicity included the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, Expanded Prostate Cancer Index Composite (EPIC) self-assessment questionnaires, and proctoscopic examinations. The mean EPIC bowel scores changed significantly through the course of therapy and follow-up (p < 0.0001), with a progressive decrease in scores at Weeks 5 and 7 of treatment, a partial recovery at 3 months, and a correlation to the gold standard RTOG grade (p = 0.004). Proctoscopic toxicity scores were low, did not vary over time, and did not correlate with either EPIC or RTOG scores. The EPIC questionnaire measurements are most sensitive to changes in acute bowel toxicity through a course of radiotherapy and correlate with RTOG acute toxicity scores. Endoscopic examination of the rectal mucosa at the end and immediate follow-up of a course of therapy does not seem to be informative or reproducible between observers in the acute setting.

Acute and late complications after radiotherapy for prostate cancer: Results of a multicenter randomized trial comparing 68 Gy to 78 Gy

To compare acute and late gastrointestinal (GI) and genitourinary (GU) side effects in prostate cancer patients randomized to receive 68 Gy or 78 Gy. Between June 1997 and February 2003, 669 prostate cancer patients were randomized between radiotherapy with a dose of 68 Gy and 78 Gy, in 2 Gy per fraction and using three-dimensional conformal radiotherapy. All T stages with prostate-specific antigen (PSA) <60 ng/mL were included, except any T1a and well-differentiated T1b-c tumors with PSA < or =4 ng/mL. Stratification was done for four dose-volume groups (according to the risk of seminal vesicles [SV] involvement), age, hormonal treatment (HT), and hospital. The clinical target volume (CTV) consisted of the prostate with or without the SV, depending on the estimated risk of SV invasion. The CTV-planning target volume (PTV) margin was 1 cm for the first 68 Gy and was reduced to 0.5 cm (0 cm toward the rectum) for the last 10 Gy in the 78 Gy arm. Four Dutch hospitals participated in this Phase III trial. Evaluation of acute and late toxicity was based on 658 and 643 patients, respectively. For acute toxicity (<120 days), the Radiation Therapy Oncology Group (RTOG) scoring system was used and the maximum score was reported. Late toxicity (>120 days) was scored according to the slightly adapted RTOG/European Organization for Research and Treatment of Cancer (EORTC) criteria. The median follow-up time was 31 months. For acute toxicity no significant differences were seen between the two randomization arms. GI toxicity Grade 2 and 3 was reported as the maximum acute toxicity in 44% and 5% of the patients, respectively. For acute GU toxicity, these figures were 41% and 13%. No significant differences between both randomization arms were seen for late GI and GU toxicity, except for rectal bleeding requiring laser treatment or transfusion (p = 0.007) and nocturia (p = 0.05). The 3-year cumulative risk of late RTOG/EORTC GI toxicity grade > or =2 was 23.2% for 68 Gy, and 26.5% for 78 Gy (p = 0.3). The 3-year risks of late RTOG/EORTC GU toxicity grade > or =2 were 28.5% and 30.2% for 68 Gy and 78 Gy, respectively (p = 0.3). Factors related to acute GI toxicity were HT (p < 0.001), a higher dose-volume group (p = 0.01), and pretreatment GI symptoms (p = 0.04). For acute GU toxicity, prognostic factors were: pretreatment GU symptoms (p < 0.001), HT (p = 0.003), and prior transurethral resection of the prostate (TURP) (p = 0.02). A history of abdominal surgery (p < 0.001) and pretreatment GI symptoms (p = 0.001) were associated with a higher incidence of late GI grade > or =2 toxicity, whereas HT (p < 0.001), pretreatment GU symptoms (p < 0.001), and prior TURP (p = 0.006) were prognostic factors for late GU grade > or =2. Raising the dose to the prostate from 68 Gy to 78 Gy resulted in higher incidences of acute and late GI and GU toxicity, but these differences were not significant, except for late rectal bleeding requiring treatment and late nocturia. Other factors than the studied dose levels appeared to be important in predicting toxicity after radiotherapy, especially previous surgical interventions (abdominal surgery or TURP), hormonal therapy, and the presence of pretreatment symptoms.

Does aqueous or sucralfate cream affect the severity of erythematous radiation skin reactions? A randomised controlled trial

Background and purposeEvidence on which to base decisions about the management of radiation skin reactions is lacking. The purpose of this study was to investigate whether sucralfate or aqueous cream reduced acute skin toxicity during radiotherapy to the head and neck, breast or anorectal area (phase A), and to evaluate the effect of hydrogels and dry dressings on moist desquamation (phase B). This paper presents the results of phase A. Patients and methodsThree hundred and fifty seven patients were randomised to apply aqueous cream, sucralfate cream or no cream to the irradiated area from day one of radical radiotherapy treatment. All patients were instructed to wash using unperfumed soap. Acute skin toxicity was measured using a modified radiation therapy oncology group (RTOG) score, reflectance spectrophotometry, patient diary card and dermatology life quality index (DLQI). A cost minimisation approach was used to compare the costs of each skin care approach. ResultsNo consistent differences were found in the severity of skin reactions or levels of discomfort suffered by patients in each of the randomised groups. Patients with a higher body mass index, who smoked, received concomitant chemotherapy, boost or bolus during treatment were more likely to develop skin reactions. ConclusionsThere is no evidence to support the prophylactic application of either of the creams tested for the prevention of radiation skin reactions. Our results show that it is possible to predict which patients are at greatest risk of skin reactions. We suggest that known risk factors should be incorporated into future study protocols.

Prediction of Genitourinary Tract Morbidity After Brachytherapy for Prostate Adenocarcinoma

To investigate whether preoperative genitourinary variables in patients undergoing brachytherapy for localized prostate adenocarcinoma could predict postoperative genitourinary tract morbidity. We retrospectively reviewed medical records of 105 men who received either iodine 125 or palladium 103 radioactive seed implants with or without external beam radiotherapy or hormone blockade from January 1, 1998, through December 31, 2000, at the Mayo Clinic in Jacksonville, Fla. Patients with one or more of the following were classified as having a high risk of postoperative genitourinary tract morbidity: American Urological Association symptom scores greater than 15, maximum urinary flow rate less than 10 mL/s, postvoid residual urinary volume greater than 100 mL, or prostate volume greater than 40 cm3. Of the 105 men, 59 (56%) were classified as high risk and 46 (44%) as low risk. Mean follow-up after brachytherapy was 23.6 months. Modified Radiation Therapy Oncology Group scores were used to assess postoperative genitourinary tract morbidity. The term significant genitourinary tract morbidity was applied to patients with a Radiation Therapy Oncology Group grade of 3 or 4 after at least 6 months of follow-up. Significant morbidity occurred in 37% of high-risk vs 15% of low-risk patients (P = .006). In high-risk patients, transurethral resection or incision of the prostate was required in 5 patients, urethral dilation in 4, direct-vision internal urethrotomy in 1, and placement of a suprapubic catheter in 1. In low-risk patients, transurethral incision of the prostate was required in only 1 patient. Urinary flow rate was a significant individual predictor of postoperative morbidity (P = .03). A combination of urinary flow rate, prostate volume, postvoid residual urinary volume, and American Urological Association symptom score can help identify patients with underlying voiding dysfunction. Urinary flow rate was a statistically significant predictor of genitourinary tract morbidity after brachytherapy for localized prostate adenocarcinoma. Patients and physicians should consider these factors before a patient decides to undergo brachytherapy.

Impact of radiation therapy on acute toxicity in breast conservation therapy for early breast cancer.

To document the acute toxicity experienced by women receiving radiation therapy as part of breast-conservation therapy (BCT) for early breast cancer. A retrospective review was undertaken of the medical records of 234 consecutive women managed with radiation therapy for BCT over a 2-year period. A policy of formal acute toxicity documentation was present during this period with descriptive measures as well as the Radiation Therapy Oncology Group (RTOG) acute toxicity scoring system. Cutaneous moist desquamation, peak RTOG score, breast oedema and chemotherapy dose intensity were end points assessed. Patient and treatment characteristics were investigated for their association with study end points using Chi-squared and logistic regression analyses. A total of 223 (95%) of women had data available for analysis. All women were treated with tangential fields on megavoltage linear accelerators. Eighty-three (37.2%) women had systemic chemotherapy either delivered simultaneously in 58 and sequentially in 25. Moist desquamation occurred in 70 (31.4%) women; principally in the inframammary fold only in 43 (19.3%). Only 12 (5.4%) had a confluent moist reaction. Two hundred and ten (94%) women had a peak RTOG skin grade of 2 or less. Breast oedema was evident at treatment end in 46 (20.5%). On univariate analysis, physical factors, such as patient weight (P<0.001) and breast size (P<0.001), were significantly associated with moist desquamation, as were the volume of breast resected (P=0.02) and the use of chemotherapy (P=0.03). Only the physical factors remained significant on multivariate analysis. The presence of breast oedema was associated with surgical factors such as post-operative oedema (P<0.001) and infective complications (P<0.001). The use of concurrent chemoradiotherapy did not affect chemotherapy dose intensity, nor did the presence of moist desquamation increase the risk of febrile complications in chemotherapy-related neutropenia. This study confirms the relatively low incidence of significant acute toxicity experienced by women during radiation therapy as part of BCT. These study data should assist surgeons and women in the decision-making process for BCT.

Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores

Purpose: The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force subjective, objective, management, and analytic (LENT/SOMA) scores were compared in a group of breast cancer patients. The impact of the classification system on grading late effects was evaluated. Methods and materials: Telangiectasia, skin pigmentation, and fibrosis were scored according to both LENT/SOMA and RTOG criteria. The results were compared with respect to up- or downgrading and correlated (Spearman’s ρ). Other side effects were recorded using LENT/SOMA criteria. Interobserver variability was calculated with Cohen’s κ. Two hundred fifty-nine subsequent relapse-free patients who underwent breast-conserving therapy between 1981 and 1995 were examined. The median dose of radiotherapy to the breast was 55 Gy. Adjuvant chemotherapy was given to 31 patients and tamoxifen to 52 patients. The median follow-up was 8 years. RTOG skin and s.c. tissue scales and LENT/SOMA breast and pigmentation scales were used. Two doctors examined 45 patients jointly. Results: Of all patients, 20% had telangiectasia, 22% pigmentation, 43% fibrosis, 4% breast edema, 77% retraction/atrophy, and 54% pain. In comparison, when LENT/SOMA criteria were used, telangiectasia and pigmentation were upgraded in 34% and 36%, respectively, and telangiectasia was downgraded in 45%. Fibrosis correlated well (Spearman’s ρ 0.78, p = 0.01). An additional 356 side effects, mainly retraction/atrophy were observed in 226 patients using LENT/SOMA criteria. Interobserver variability was similar for both classification systems and ranged from Cohen’s κ 0.3 (retraction) to 0.91 (telangiectasia). Conclusion: LENT/SOMA criteria seem to be the better tool in grading and recording late radiation toxicity compared with the RTOG scale. There was some upgrading with the RTOG score when skin toxicity is evaluated. In contrast, fibrosis scores correlated very well. Adjustments of the LENT/SOMA scoring system should be considered to standardize reporting of late radiation morbidity.

Rectal function following brachytherapy with or without supplemental external beam radiation: Results of two prospective randomized trials

Purpose To evaluate the effect of isotope and supplemental external beam radiation therapy (XRT) on brachytherapy-related rectal morbidity, using prospective, patient-administered quality of life (QOL) assessments. Methods and materials Two hundred thirteen consecutive patients (median follow-up 22 months) were implanted on 2 prospective randomized brachytherapy trials evaluating the effect of isotope for low-risk patients and different doses of supplemental XRT for patients with higher risk features. Treatment-related rectal morbidity was evaluated by modified Radiation Therapy Oncology Group (RTOG) criteria and the multifactorial Rectal Function Assessment Score (R-FAS). Clinical, treatment and dosimetric parameters evaluated included patient age, diabetes, hypertension, tobacco consumption, clinical stage, prostate ultrasound volume, elapsed time since implant, hormonal manipulation, supplemental XRT, isotope, treatment planning volume, and values of the minimum dose received by 90% of the prostate gland (D 90), the percent prostate volume receiving 100%, 150%, and 200% of the minimum peripheral dose (V 100/150/200), rectal implant doses (V 75/100/125/150 and D 5/10/25/50) and rectal XRT doses (D 5/10/25/50/75). Results Using the RTOG instrument, rectal morbidity peaked at 1 month. The pre- and most recent postimplant median RTOG scores were 0 and 0, respectively. The pre- and postimplant R-FAS scores were 2.41 and 3.83, respectively. With time, the rectal scores for both instruments improved and approached baseline. In multivariate analysis, only the rectal dosimetry variable D 5 predicted for bowel function when using the R-FAS instrument. No clinical, treatment, or dosimetric parameters predicted for bowel function when using the RTOG survey. No patient required surgical intervention for rectal complications. Conclusions The multifactorial R-FAS elucidated fine gradations in bowel function of a severity less than RTOG Grade 3 morbidity. Of multiple clinical, treatment, and dosimetric parameters evaluated, only the minimum dose received by 5% of the rectum (D5) correlated with rectal dysfunction via the R-FAS instrument, while none of the evaluated parameters predicted for bowel dysfunction using the RTOG survey. Following permanent prostate brachytherapy, the ability to discern subtle changes in rectal function is dependent on the sensitivity of the survey instrument.

The use of rectal balloon during the delivery of intensity modulated radiotherapy (IMRT) for prostate cancer: more than just a prostate gland immobilization device?

The purpose of this study was to investigate the role of a rectal balloon for prostate immobilization and rectal toxicity reduction in patients receiving dose-escalated intensity-modulated radiotherapy for prostate cancer. Patients with localized prostate cancer who were undergoing intensity-modulated radiotherapy were treated in a prone position, immobilized with a customized Vac-Lok bag (MED-TEC, Orange City, IA). A rectal balloon with 100 cc of air was used to immobilize the prostate. The prostate displacements were measured using computed tomography (CT)-CT fusion on 10 patients who received radioactive seed implant before intensity-modulated radiotherapy. They were scanned twice weekly during 5 weeks of intensity-modulated radiotherapy, and breathing studies were also performed. Rectal toxicity was evaluated by use of Radiation Therapy Oncology Group scoring in 100 patients. They were treated to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). Dose-volume histogram of the rectum was assessed. A film phantom was constructed to simulate the 4-cm diameter air cavity that was created by the rectal balloon. Kodak XV2 films (Rochester NY) were used to measure and compare dose distribution with and without the air cavity. A fraction of 1.25 Gy was delivered to the phantom at isocenter with 15-MV photons by use of the NOMOS Peacock system and the MIMiC treatment delivery system (Sewickley, PA). The anterior-posterior and lateral prostate displacements were minimal, on the order of measurement uncertainty (approximately 1 mm). The standard deviation of superior-inferior displacement was 1.78 mm. Breathing studies showed no organ displacement during normal breathing when the rectal balloon was in place. The rectal toxicity profile was very favorable: 83% (83/100) patients had no rectal complaint, and 11% and 6% had grade 1 and 2 toxicity, respectively. Dose-volume histogram analysis revealed that in all of the patients, no more than 25% of the rectum received 70 Gy or greater. As visualized by film dosimetry, the dose at air-tissue interface was approximately 15% lower than that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, the differential was approximately 8% and 5%, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal, with or without the air cavity. The use of a rectal balloon during intensity-modulated radiotherapy significantly reduces prostate motion. Prostate immobilization thus allows a safer and smaller planning target volume margin. It has also helped spare the anterior rectal wall (by its dosimetric effects) and reduced the rectal volume that received high-dose radiation (by rectal wall distension). All these factors may have further contributed to the decreased rectal toxicity achieved by intensity-modulated radiotherapy, despite dose escalation and higher-than-conventional fraction size.

Indicators of late normal tissue response after radiotherapy for head and neck cancer: fibroblasts, lymphocytes, genetics, DNA repair, and chromosome aberrations

Purpose: To investigate the relationship between late tissue response after radiotherapy, cellular sensitivity and DNA repair capacity measured in dermal fibroblasts and chromosomal aberrations measured in lymphocytes. The study was in particular designed to compare cellular parameters of patients with maximum differences in late tissue reactions. Materials and methods: The study was performed with 16 pair-wise matched head and neck cancer patients 2–7 years after curative therapy exhibiting maximum differences (grade 1 vs. grade 3) in late normal tissue reactions. Clinical endpoints were fibrosis, telangiectasia, mucositis and xerostomia using the radiation therapy oncology group score. Patients with grade 3 reactions were tested for mutations in ataxia telangiectasia (AT), Nijmegen Breakage Syndrome (NBS), MRE11, RAD50 and DNA ligase IV genes by means of polymerase chain reaction-single-strand conformation polymorphism and sequencing analysis. Skin fibroblasts obtained from biopsies were used to determine the cellular sensitivity by colony formation and the induction and repair of DNA double-strand breaks (dsb) using constant-field gel electrophoresis. Lymphocytes were taken to measure chromosomal damage either in metaphase using conventional chromosome analysis or in G 0 using premature chromosome condensation (PCC)-technique. Results: Patients with extreme late reactions (grade 3) showed no evidence for an AT, NBS, MRE11 or RAD50 mutation. Studies with fibroblasts revealed that extreme late reactions were associated neither with a pronounced cellular radiosensitivity nor with a difference in dsb repair capacity. In contrast, there was a significant difference in chromosomal damage measured in lymphocytes. After in vitro irradiation with 6 Gy, lymphocytes taken from overreacting patients showed on average a significantly higher number of lethal aberrations than lymphocytes isolated from patients with mild reactions (7.2±0.8 vs. 5.0±0.3). Similar differences were found for PCC fragments. Conclusion: This study suggests that lymphocytes are more promising than fibroblasts to predict patient's normal tissue response after radiotherapy.

Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies

Background and purpose: The incidence and extent of radiation esophagitis were assessed endoscopically in patients treated with concurrent chemoradiotherapy. Patients and methods: Eighty-two patients who received thoracic radiotherapy for lung, thymic, or esophageal cancer were investigated endoscopically from July 1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated with radiation alone, and the others were treated with concurrent chemoradiotherapy. Esophageal endoscopy was performed during or just after radiotherapy. The presence of radiation esophagitis was assessed and assigned an endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation morbidity score. Results: A correlation was seen between endoscopic and RTOG scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3 esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the concurrent chemoradiotherapy group, whereas it did not occur in any patient in the radiation alone group ( P=0.004). Conclusions: Our results suggest that (1) RTOG score correlates closely to esophageal mucosal damage, and (2) more severe esophagitis occurs in those undergoing radiotherapy alone.

Prophylaxis of radiogenic sialadenitis and mucositis by coumarin/troxerutine in patients with head and neck cancer – a prospective,randomized, placebo-controlled, double-blind study

To study the efficacy of coumarin/troxerutine for the protection of salivary glands and mucosa during irradiation. Design: Prospective, randomized, placebo-controlled, double-blind trial. Setting: University hospital, Germany. Patients: 48 patients who had radiotherapy to the head and neck. Main outcome measures: Salivary gland scintigraphy and acute side-effects of radiotherapy (Radiation Therapy Oncology Group (RTOG) score). Results: 23 patients (11 experimental, 12 placebo) completed the study. The global efficacy measure combining scintigraphy and RTOG score favoured the experimental arm (P= 0.07). The RTOG score showed significantly fewer acute side-effects of radiation in the experimental arm (P< 0.05). Conclusion: The results suggest that coumarin/troxerutine have a favourable effect in the treatment of radiogenic sialadenitis and mucositis.

Intensity modulated radiation therapy (IMRT) following prostatectomy: more favorable acute genitourinary toxicity profile compared to primary IMRT for prostate cancer

Purpose: To report our initial experience on postprostatectomy IMRT (PPI), addressing acute genitourinary (GU) toxicity in comparison to primary IMRT (PI) for prostate cancer. Methods and Materials: From April 1998 to December 1999, 40 postprostatectomy patients were treated with intensity modulated radiation therapy (IMRT) to a median prescribed dose of 64 Gy (mean dose of 69 Gy). The Radiation Therapy Oncology Group (RTOG) scoring system was used to assess acute GU toxicity. Target volume and maximum and mean doses were evaluated. The mean doses to the bladder and irradiated bladder volume receiving >65 Gy were assessed. These were compared to those of 125 patients treated with PI to a prescribed dose of 70 Gy (mean dose of 76 Gy). Results: The acute GU toxicity profile is more favorable in the PPI group with 82.5% of Grade 0–1 and 17.5% of Grade 2 toxicity compared to 59.2% and 40.8%, respectively, in the PI group ( p < 0.001). There was no Grade 3 or higher toxicity in either group. The target volume was larger in the PPI group, while the maximum and mean doses to the target were higher in the PI group. The mean dose delivered to the bladder was higher in the PPI group. The irradiated bladder volume receiving >65 Gy was significantly larger in the PI group ( p < 0.001). Conclusions: PPI can be delivered with acceptable acute GU toxicity. The larger PPI target volume may be related to the difficulty in delineating prostatic fossa. Despite a larger target volume and a higher mean dose to the bladder, PPI produced a more favorable acute GU toxicity profile. This may be related to a combination of lower mean and maximum doses and smaller bladder volumes receiving >65 Gy in the PPI group, as well as urethral rather than bladder irradiation. The findings have implications in the evaluation of IMRT treatment plan for prostate cancer, whereby the irradiated bladder volumes above 65 Gy may be more meaningful than the mean dose to the bladder. Longer term toxicity results are awaited.

Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma

The purpose of this study was to analyze the tolerance and efficacy of full dose reirradiation combined with chemotherapy in patients with head and neck carcinoma (HNC) with a high risk of recurrence after salvage surgery. Between 1991 and 1996, 25 patients having a recurrence or a second primary tumor in a previously irradiated area (> 45 grays [Gy]) were entered in this prospective study. All of them received salvage surgery and had a positive surgical margin and/or lymph node involvement with capsular rupture (N+R+). Adjuvant radiochemotherapy was given, delivering 60 Gy per 30 fractions with concomitant hydroxyurea and 5-fluorouracil. The median total cumulative dose of the 2 irradiations was 118 Gy. The median follow-up after the second irradiation was 66 months. During the reirradiation course, Grade 3 and 4 mucositis were observed in 40% and 12%, respectively. Analysis of late effects (> 6 months after reirradiation) showed that 16% of the patients had osteoradionecrosis and 40% had Grade 2-3 cervical fibrosis (Radiation Therapy Oncology Group scoring system). The patterns of failure were as follows: local only (n = 9), lymph node only (n = 2), local and lymph node only (n = 1), and metastatic (n = 4). The 4-year survival rate after reirradiation was 43% (95% confidence interval, 25-62). Full dose reirradiation combined with chemotherapy after salvage surgery in high risk patients with HNC was feasible with an "acceptable" toxicity and led to a relatively good 5-year survival rate. These results prompted the authors to initiate a multicentric randomized trial that is ongoing (GETTEC-GORTEC 99-01) to evaluate the benefit of adjuvant radiochemotherapy in these types of patients.

Radiation myelopathy in over-irradiated patients: MR imaging findings

The objective of this work is to report the MRI findings in patients with radiation myelopathy due to accidental local over-irradiation syndrome. Eight patients (seven males and one female) were suffering from over-irradiation syndrome as a result of treatments from a malfunctioning linear electron accelerator. The mean accidental estimated dose was 136 Gy delivered to the "open-neck" (seven cases) and to the thoracic wall (one case), during a mean of 5.4 sessions (range 1-9 sessions). Paresthesia and weakness in the upper extremities were the earliest symptoms (87.5 %), with evolution to paralysis in all patients. No patient is alive (mean survival time 64 days). In all cases MRI was negative for neurologic lesions in the acute phase ( < 90 days from irradiation; Radiation Therapy Oncology Group scoring system). Late signs of radiation myelitis manifested as high-intensity signals on T2-weighted images in three patients, and as Gd-DTPA enhancement of T1-weighted images in one case. Autopsies performed on four patients who died in acute phase showed morphologic alterations in white matter: edema in 75 %, and necrosis and glial reaction as well as obliterative vasculitis in all cases. In cases of over-irradiation, MRI may be normal in acute phase even if the patients have severe neurologic deficit, as positive MRI findings appear only in delayed radiation myelitis.