CT Based 3-Dimensional Treatment Planning of Intracavitary Brachytherapy for Cancer of the Cervix : Comparison between Dose-Volume Histograms and ICRU Point Doses to the Rectum and Bladder

Background: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT). Materials and Methods: Between March2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose (DMax) to rectum was the highest recorded dose at one of these five points. Using the HDRplus 2.6 brachyhtherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded (D2cc) for all individual fractions. The mean D2cc of rectum was compared to the means of ICRU rectal point and rectal DMax using the Student’s t-test. The mean D2cc of bladder was compared with the mean ICRU bladder point using the same statistical test .The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (α/β value of 10 Gy for target, 3 Gy for organs at risk). Results: The total prescribed dose was 77.5 Gyα/β10. The mean dose to the rectum was 4.58±1.22 Gy for D2cc, 3.76±0.65 Gy at DICRU and 4.75±1.01 Gy at DMax. The mean rectal D2cc dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48 -1.19Gy). The mean EQD2 was 68.52±7.24 Gyα/β3 for D2cc, 61.71±2.77 Gyα/β3 at DICRU and 69.24±6.02Gyα/β3 at DMax. The mean ratio of D2cc rectum to DICRU rectum was 1.25 and the mean ratio of D2cc rectum to DMax rectum was 0.98 for all individual fractions. The mean dose to the bladder was 6.00±1.90 Gy for D2cc and 5.10±2.03 Gy at DICRU. However, the mean D2cc dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25Gy). The mean EQD2 was 81.85±13.03 Gyα/β3 for D2cc and 74.11±19.39 Gyα/β3 at DICRU. The mean ratio of D2cc bladder to DICRU bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose. Conclusions: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder pointmay be a reasonable surrogate for the D2cc and rectal DMax for D2cc. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the D2cc.     

Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: impact of rectal dose in high-dose-rate brachytherapy on occurrence of grade 2 or worse rectal bleeding

PURPOSE: To evaluate the incidence of Grade 2 or worse rectal bleeding after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiotherapy (EBRT), with special emphasis on the relationship between the incidence of rectal bleeding and the rectal dose from HDR brachytherapy. METHODS AND MATERIALS: The records of 100 patients who were treated by HDR brachytherapy combined with EBRT for > or =12 months were analyzed. The fractionation schema for HDR brachytherapy was prospectively changed, and the total radiation dose for EBRT was fixed at 51 Gy. The distribution of the fractionation schema used in the patients was as follows: 5 Gy x 5 in 13 patients; 7 Gy x 3 in 19 patients; and 9 Gy x 2 in 68 patients. RESULTS: Ten patients (10%) developed Grade 2 or worse rectal bleeding. Regarding the correlation with dosimetric factors, no significant differences were found in the average percentage of the entire rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose from EBRT between those with bleeding and those without. The average percentage of the entire rectal volume receiving 10%, 30%, 50%, 80%, and 90% of the prescribed radiation dose from HDR brachytherapy in those who developed rectal bleeding was 77.9%, 28.6%, 9.0%, 1.5%, and 0.3%, respectively, and was 69.2%, 22.2%, 6.6%, 0.9%, and 0.4%, respectively, in those without bleeding. The differences in the percentages of the entire rectal volume receiving 10%, 30%, and 50% between those with and without bleeding were statistically significant. CONCLUSIONS: The rectal dose from HDR brachytherapy for patients with prostate cancer may have a significant impact on the incidence of Grade 2 or worse rectal bleeding.     

Dosimetric parameters that predict late rectal complications after curative radiotherapy in patients with uterine cervical carcinoma

BACKGROUND: Late rectal complication (LRC) was a major late complication in patients with uterine cervical carcinoma who were treated with a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary irradiation (HDR-ICR). For the current study, the authors retrospectively evaluated dosimetric parameters that were correlated with LRC > or = Grade 2 in patients with uterine cervical carcinoma who were treated with curative radiotherapy, and they analyzed the appropriate dose estimates to the rectum that were predictive for LRC > or = Grade 2. METHODS: Between July 1994 and September 2002, 157 patients who were diagnosed with Stage IB-IIIB cervical carcinoma and were treated with definitive radiotherapy were included. EBRT (41.4-66 grays [Gy] in 23-33 fractions) to the whole pelvis was delivered to all patients, with midline shielding performed after a 36-50.4 Gy external dose. HDR-ICR (21-39 Gy in 6-13 fractions to Point A) was administered at a rate of 2 fractions weekly after midline shielding of EBRT. LRC was scored using Radiation Therapy Oncology Group criteria. The total biologically effective dose (BED) at specific points, such as Point A (BED(Point A)), rectal point (BED(RP)), and maximal rectal point (BED(MP)), was determined by a summation of the EBRT and HDR-ICR components, in which the alpha/beta ratio was set to 3. Analyzed parameters included patient age, tumor size, stage, concurrent chemotherapy, ICR fraction size, RP ratio (dose at the rectal point according to the Point A dose), MP ratio (dose at the maximal rectal point according to the Point A dose), EBRT dose, BED(Point A), BED(RP), and BED(MP). RESULTS: The 5-year actuarial overall rate of LRC > or = Grade 2 in all patients was 18.4%. Univariate analysis showed that the RP ratio, MP ratio, EBRT dose, BED(Point A), BED(RP), and BED(MP) were correlated with LRC > or = Grade 2 (P < 0.05). Multivariate analysis showed that, of all clinical and dosimetric parameters evaluated, only BED(RP) was correlated with LRC > or = Grade 2 (P = 0.009). The 5-year actuarial rate of LRC > or = Grade 2 was 5.4% in patients with a BED(RP) < 125 Gy(3) and 36.1% in patients with a BED(RP) > or = 125 Gy(3) (P < 0.001). CONCLUSIONS: BED(RP) was a useful dosimetric parameter for predicting the risk of LRC > or = Grade 2 and should be limited to < 125 Gy(3) whenever possible to minimize the risk of LRC > or = Grade 2 in patients with uterine cervical carcinoma who are treated with a combination of EBRT and HDR-ICR. Cancer 2005.     

Computed tomography-based high-dose-rate intracavitary brachytherapy for uterine cervical cancer: preliminary demonstration of correlation between dose-volume parameters and rectal mucosal changes observed by flexible sigmoidoscopy

PURPOSE: To compare the dose-volume histogram (DVH) parameters obtained by three-dimensional gynecologic brachytherapy planning with the rectosigmoid mucosal changes observed by flexible sigmoidoscopy. METHODS AND MATERIALS: Between January 2004 and July 2005, 71 patients with International Federation of Gynecology and Obstetrics Stage IB-IIIB uterine cervical cancer underwent computed tomography-based high-dose-rate intracavitary brachytherapy. The total dose (external beam radiotherapy [RT] plus intracavitary brachytherapy) to the International Commission of Radiation Units and Measurements rectal point (ICRU(RP)) and DVH parameters for rectosigmoid colon were calculated using the equivalent dose in 2-Gy fractions (alpha/beta = 3 Gy). Sigmoidoscopy was performed every 6 months after RT, with the 6-scale scoring system used to determine mucosal changes. RESULTS: The mean values of the DVH parameters and ICRU(RP) were significantly greater in patients with a score of > or =2 than in those with a score <2 at 12 months after RT (ICRU(RP), 71 Gy(alpha/beta3) vs. 66 Gy(alpha/beta3), p = 0.02; D(0.1cc), 93 Gy(alpha/beta3) vs. 85 Gy(alpha/beta3), p = 0.04; D(1cc), 80 Gy(alpha/beta3) vs. 73 Gy(alpha/beta3), p = 0.02; D(2cc), 75 Gy(alpha/beta3) vs. 69 Gy(alpha/beta3), p = 0.02). The probability of a score of > or =2 showed a significant relationship with the DVH parameters and ICRU(RP) (ICRU(RP), p = 0.03; D(0.1cc), p = 0.05; D(1cc), p = 0.02; D(2cc), p = 0.02). CONCLUSION: Our preliminary data have shown that DVH values of the rectosigmoid colon obtained by computed tomography-based three-dimensional brachytherapy planning are reliable and predictive of score > or =2 rectosigmoid mucosal changes.     

Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: analysis of dose and fractionation schedule

PURPOSE: To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer. METHODS: Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy(10) (range: 48-76.8 Gy(10)) for early disease, and 76.8 Gy(10) (range: 38.4-86.4 Gy(10)) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy(3) (range: 59.1-134.4 Gy(3)) at the rectum, 97.8 Gy(3) (range: 54.6-130.4 Gy(3)) at the bladder, and 324 Gy(3) (range: 185.5-618 Gy(3)) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED. RESULTS: The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose-response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade > or =1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis (p < 0.0001) and enterocolitis (p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy(10) at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013). CONCLUSIONS: In view of the therapeutic ratio, cumulative BED 70-80 Gy(10) at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100-120 Gy(3) to prevent late rectal complication.     

Comparison between CT-based volumetric calculations and ICRU reference-point estimates of radiation doses delivered to bladder and rectum during intracavitary radiotherapy for cervical cancer

PURPOSE: To compare CT-based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the uterine cervix treated with definitive low-dose-rate intracavitary radiotherapy (ICRT). METHODS AND MATERIALS: Between November 2001 and March 2003, 60 patients were prospectively enrolled in a pilot study of ICRT with CT-based dosimetry. Most patients underwent two ICRT insertions. After insertion of an afterloading ICRT applicator, intraoperative orthogonal films were obtained to ensure proper positioning of the system and to facilitate subsequent planning. Treatments were prescribed using standard two-dimensional dosimetry and planning. Patients also underwent helical CT of the pelvis for three-dimensional reconstruction of the radiation dose distributions. The systems were loaded with 137Cs sources using the Selectron remote afterloading system according to institutional practice for low-dose-rate brachytherapy. Three-dimensional dose distributions were generated using the Varian BrachyVision treatment planning system. The rectum was contoured from the bottom of the ischial tuberosities to the sigmoid flexure. The entire bladder was contoured. The minimal doses delivered to the 2 cm3 of bladder and rectum receiving the highest dose (DBV2 and DRV2, respectively) were determined from dose-volume histograms, and these estimates were compared with two-dimensionally derived estimates of the doses to the corresponding ICRU reference points. Results: A total of 118 unique intracavitary insertions were performed, and 93 were evaluated and the subject of this analysis. For the rectum, the estimated doses to the ICRU reference point did not differ significantly from the DRV2 (p = 0.561); the mean (+/- standard deviation) difference was 21 cGy (+/- 344 cGy). The median volume of the rectum that received at least the ICRU reference-point dose was 2.1 cm3. In 66 (71%) of 93 cases, <5 cm3 was treated to this dose. However, for the bladder, the estimated doses to the ICRU reference point were significantly lower than the D(BV2) (p <0.001); the mean difference was 680 cGy (+/- 543 cGy). The median volume of the bladder that received at least the ICRU reference-point dose was 13.0 cm3. CONCLUSIONS: Our data suggest that the estimated dose to the ICRU rectal point may be a reasonable surrogate for the DRV2. However, this result may not be applicable to other treatment guidelines and ICRT applicator systems. In contrast, the dose to the ICRU bladder point does not appear to be a reasonable surrogate for the DBV2. Correlation with late complications are needed to define the role of three-dimensional dosimetry in treatment planning.     

Rectal morbidity following I-125 prostate brachytherapy in relation to dosimetry

BACKGROUND: To investigate rectal morbidity after I-125 prostate brachytherapy and to analyze predictive factors of rectal morbidity. METHODS: A group of 227 consecutive patients with localized prostate cancer were treated with I-125 prostate brachytherapy with or without external beam radiotherapy (EBRT) between September 2003 and January 2005. Rectal morbidity (diarrhea, bleeding and pain) was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Dosimetry was based on computerized tomography (CT) scan 1 month post-implant. The clinical, treatment-related and dosimetric factors were evaluated for the risk of grade 2 rectal morbidity. Rectal dosimetric factors included the rectal volume that received >100% and 150% of the prescribed dose, and the maximal rectal dose which was defined as the sum of the minimal dose received by 1% of the rectum volume and the prescribed dose of EBRT. RESULTS: Grade 2 rectal bleeding occurred in 10 (4.4%): for nine patients within the first year and for one patient between the first and second year. Grade 2 diarrhea occurred in one patient (0.4%) within the first year. No patient reported grade 2 pain. In the univariate analysis with grade 2 rectal bleeding, there were significant correlations with number of seeds, supplemental EBRT, and all of the rectal dosimetric parameters. On subsequent multivariate analysis, the only significant factor was the maximal rectal dose (P < 0.001). Rectal dose > 160 Gy was correlated to grade 2 rectal morbidity. All the patients with rectal dose > 160 Gy received EBRT. CONCLUSIONS: Manifestations of rectal morbidity are acceptable events after I-125 prostate brachytherapy. Rectal dose-volume histogram for the brachytherapy is a predictive method for assessing the risk of developing grade 2 rectal bleeding. Delivery of the rectal dose should not exceed 160 Gy in order to avoid rectal complications.     

Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation.

PURPOSE: To quantitate the impact of total doses of irradiation, dose rate, and ratio of doses to bladder or rectum and point A on sequelae in patients treated with irradiation alone for cervical cancer. METHODS AND MATERIALS: Records were reviewed of 1456 patients (Stages IB-IVA) treated with external-beam irradiation plus two low-dose rate intracavitary insertions to deliver 70 to 90 Gy to point A. Follow-up was obtained in 98% of patients (median, 11 years; minimum, 3 years; maximum, 30 years). The relationships among various dosimetry parameters and Grade 2 or 3 sequelae were analyzed. RESULTS: In Stage IB, the frequency of patients developing Grade 2 morbidity was 9%, and Grade 3 morbidity, 5%; in Stages IIA, IIB, III, and IVA, Grade 2 morbidity was 10% to 12% and Grade 3 was 10%. The most frequent Grade 2 sequelae were cystitis and proctitis (0.7% to 3%). The most common Grade 3 sequelae were vesicovaginal fistula (0.6% to 2% in patients with Stage I-III tumors), rectovaginal fistula (0.8% to 3%), and intestinal obstruction (0.8% to 4%). In the bladder, doses below 80 Gy correlated with less than 3% incidence of morbidity and 5% with higher doses (p = 0.31). In the rectosigmoid, the incidence of significant morbidity was less than 4% with doses below 75 Gy and increased to 9% with higher doses. For the small intestine, the incidence of morbidity was less than 1% with 50 Gy or less, 2% with 50 to 60 Gy, and 5% with higher doses to the lateral pelvic wall (p = 0.04). When the ratio of dose to the bladder or rectum in relation to point A was 0.8 or less, the incidence of rectal morbidity was 2.5% (8 of 320) vs. 7.3% (80 of 1095) with higher ratios (p < or = 0.01); bladder morbidity was 2.3% (7 of 305) and 5.8% (64 of 1110), respectively (p = 0.02). The incidence of Grade 2 and 3 bladder morbidity was 2.9% (10 of 336) when the dose rate was less than 0.80 Gy/h, in contrast to 6.1% (62 of 1010) with higher dose rates (p = 0.07). Rectal morbidity was 2% to 5% in Stage IB, regardless of dose rate to the rectum; in Stages IIA-B and III, morbidity was 5.2% (28 of 539) with a dose rate of 0.80 Gy or less and 10.7% (37 of 347) with higher dose rates (p < 0.01). Multivariate analysis showed that dose to the rectal point was the only factor influencing rectosigmoid sequelae, and dose to the bladder point affected bladder morbidity. CONCLUSIONS: Various dosimetric parameters correlate closely with the incidence of significant morbidity in patients treated with definitive irradiation for carcinoma of the uterine cervix. Careful dosimetry and special attention to related factors will reduce morbidity to the lowest possible level without compromising pelvic tumor control.     

Predictors of severe gastrointestinal toxicity after external beam radiotherapy and interstitial brachytherapy for advanced or recurrent gynecologic malignancies

PURPOSE: The aim of this retrospective review of patients with gynecologic malignancies treated with external beam radiotherapy (EBRT) and interstitial brachytherapy was to determine the rate of Grade > or =2 rectovaginal fistula and Grade > or =4 small bowel obstruction as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. METHODS AND MATERIALS: Thirty-six patients with primary and recurrent gynecologic cancers were treated with EBRT and interstitial brachytherapy. Median doses to tumor, bladder, and rectum were 75 Gy, 61 Gy, and 61 Gy, respectively. A univariate analysis was performed to identify variables that correlated with toxicity. RESULTS: At median follow-up of 19 months, the 3-year risk of small bowel obstruction was 6%. Those patients with prior abdomino-pelvic surgery who received EBRT with antero-posterior fields had higher rates of obstruction than patients without prior abdomino-pelvic surgery or those who received EBRT with four fields (50% vs. 0%, p < 0.0001). The 3-year risk of rectovaginal fistula was 18% and was significantly higher in patients who received >76 Gy to the rectum compared with those who received < or =76 Gy (100% vs. 7%, p = 0.009). CONCLUSIONS: Patients treated with EBRT and interstitial brachytherapy after abdomino-pelvic surgery should receive EBRT with four fields and the cumulative rectal dose should be < or =76 Gy.     

The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose-rate brachytherapy

PURPOSE: This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS: From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS: After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION: Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.     

Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO stage IB uterine cervical carcinoma

: To determine the optimal dose combination scheme of external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiation (ICR) for maximizing tumor control while conferring an acceptable late complication rate in the treatment of Stage IB uterine cervical cancer.

: We retrospectively analyzed 162 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB squamous cell carcinoma of the uterine cervix who received definitive RT between May 1979 and December 1990. Before HDR-ICR, all patients received EBRT to a total dose of 40–46 Gy (median 45), administered during 4–5 weeks to the whole pelvis. HDR-ICR was given 3 times weeks to a total dose of 24–51 Gy (median 39) at point A, using a dose of 3 Gy/fraction. Central shielding from EBRT was begun after the delivery using 20–45 Gy (median 40) of the external dose. The total dose to point A, calculated by adding the EBRT biologically effective dose (BED) and the ICR BED to point A, was 74.1–118.1 Gy (mean 95.2). The rectal point dose was calculated at the anterior rectal wall at the level of the cervical os. The local control rate, survival rate, and late complication rate were analyzed according to the irradiation dose and BED.

: The initial complete response rate was 99.4%. The overall 5-year survival rate and 5-year disease-free survival rate was 91.1% and 90.9%, respectively. The local failure rate was 4.9%, and the distant failure rate was 4.3%. Late complications were mild and occurred in 23.5% of patients, with 18.5% presenting with rectal complications and 4.9% with bladder complications. The mean rectal BED (the sum of the external midline BED and the ICR rectal point BED) was lower in the patients without rectal complications than in those with rectal complications (125.6 Gy vs. 142.7 Gy, p = 0.3210). The late rectal complication rate increased when the sum of the external midline BED and the rectal BED by ICR was ≥131 Gy (p = 0.1962). However, 5-year survival rates did not increase with the external midline BED (p = 0.4093). The late rectal complication rate also increased, without a change in the survival rate, when the sum of the external midline BED and the ICR point A BED was >90 Gy.

: In treating Stage IB carcinoma of the uterine cervix with HDR-ICR, using fractions of 3 Gy, it is crucial to keep the point A BED at ≤90 Gy to minimize late rectal complications without compromising the survival rate. To achieve this goal, appropriate central shielding from EBRT is needed.     

Dose-volume impact in high-dose-rate Iridium-192 brachytherapy as a boost to external beam radiotherapy for localized prostate cancer--a phase II study.

BACKGROUND AND PURPOSE: Evaluation of dose-volume-time-related factors in 64 patients treated with high-dose-rate brachytherapy (HDR-BT) as a boost to external beam radiotherapy (EBRT) for localized prostate cancer. PATIENTS AND METHODS: Clinical parameters were correlated with morbidity scores of the EPIC (Expanded Prostate Cancer Index) questionnaire. Median time after radiotherapy (HDR-BT up to 18 Gy in two fractions and EBRT up to a median dose of 50.4 Gy) was 1.5 and 3 years (first and second questionnaire). RESULTS: A significant impact of a urethra D1 exceeding 15 Gy in at least one HDR fraction concerning urinary morbidity and a rectum D1 exceeding 6 Gy to the rectal mucosa in the first and second HDR fraction concerning the rectal bleeding rate was found. A higher number of needles was associated with lower urinary and bowel scores after 1.5 years. A prostate length >4.8 cm and a longer duration of EBRT (independently of the dose) predisposed for lower urinary and bowel scores. In contrast to a urethra D1 > 15 Gy as an independent factor, a rectum D1 > 6 Gy per HDR fraction correlated with a higher number of needles and an increased prostate length. CONCLUSIONS: To minimize morbidity in HDR-BT for prostate cancer, a maximum dose to the urethra of 15 Gy and a maximum dose to the rectal mucosa of 6 Gy is advisable. Treatment- and patient-related factors have a major impact on toxicity.     

High-dose-rate intracavitary brachytherapy: results of analyses of late rectal complications

: To examine the incidence of radiation-induced late rectal complications by analyzing the data of measured rectal doses in patients with cancer of the uterine cervix treated with high-dose-rate intracavitary brachytherapy.

: We measured doses to the rectum in 105 patients with cancer of the cervix during high-dose-rate intracavitary brachytherapy with a semiconductor dosimeter that can measure five points in the rectum simultaneously. On the basis of these measurements, equivalent doses, to which the biologically equivalent doses were converted as if given as fractionated irradiation at 2 Gy/fraction, were calculated as components of the cumulative dose at five rectal points in intracavitary brachytherapy combined with the external whole pelvic dose.

: The calculated values of equivalent doses for late effects at the rectum ranged from 15 to 100 Gy (median 60 Gy for patients who did not develop complications and 76 Gy for patients who subsequently developed Grade II or III complications). When converted to a graph of absolute rectal complication probability, the data could be fitted to a sigmoid curve. The data showed a very definite dose-response relationship, with a threshold for complications at approximately 50 Gy and the curve starting to rise more steeply at approximately 60 Gy. The steepest part of the curve had a slope equivalent to approximately 4% incidence/1 Gy increase in equivalent doses.

: The radiation tolerance dose, 5% and 50% complication probability, was about 64 and 79 Gy, respectively. Our data almost agree with the prescribed dose for the rectum for the radiation tolerance doses on the basis of the recorded human and animal data. The probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.     

Significant correlation between rectal DVH and late bleeding in patients treated after radical prostatectomy with conformal or conventional radiotherapy (66.6-70.2 Gy)

PURPOSE: Investigating the correlation between dosimetric/clinical parameters and late rectal bleeding in patients treated with adjuvant or salvage radiotherapy after radical prostatectomy. METHODS AND MATERIALS: Data of 154 consecutive patients, including three-dimensional treatment planning and dose-volume histograms (DVHs) of the rectum (including filling), were retrospectively analyzed. Twenty-six of 154 patients presenting a (full) rectal volume >100 cc were excluded from the analysis. All patients considered for the analysis (n = 128) were treated at a nominal dose equal to 66.6-70.2 Gy (ICRU dose 68-72.5 Gy; median 70 Gy) with conformal (n = 76) or conventional (n = 52) four-field technique (1.8 Gy/fr). Clinical parameters such as diabetes mellitus, acute rectal bleeding, hypertension, age, and hormonal therapy were considered. Late rectal bleeding was scored using a modified Radiation Therapy Oncology Group scale, and patients experiencing >or=Grade 2 were considered bleeders. Median follow-up was 36 months (range 12-72). Mean and median rectal dose were considered, together with rectal volume and the % fraction of rectum receiving more than 50, 55, 60, and 65 Gy (V50, V55, V60, V65, respectively). Median and quartile values of all parameters were taken as cutoff for statistical analysis. Univariate (log-rank) and multivariate (Cox hazard model) analyses were performed. RESULTS: Fourteen of 128 patients experienced >or=Grade 2 late bleeding (3-year actuarial incidence 10.5%). A significant correlation between a number of cutoff values and late rectal bleeding was found. In particular, a mean dose >or=54 Gy, V50 >or=63%, V55 >or=57%, and V60 >or=50% was highly predictive of late bleeding (p or=63% and those with V50 <63% (DVH grouping), data were fitted with a Cox regression hazard model using DVH grouping, rectal volume, and the main clinical parameters as independent variables. Results of the analysis showed that DVH grouping (relative risk 3.3; p = 0.04) and acute bleeding (relative risk 7.1; p = 0.001) are independently predictive of late bleeding. CONCLUSIONS: DVHs of the rectum are significantly correlated with late bleeding for patients irradiated at 66.6-70.2 Gy after radical prostatectomy.     

Late rectal complications evaluated by computed tomography-based dose calculations in patients with cervical carcinoma undergoing high-dose-rate brachytherapy

PURPOSE: To investigate the efficacy of dose calculations at the computed tomography (CT)-based rectal point (CTRP) as a predictive factor for late rectal complications in patients with cervical carcinoma who were treated with a combination of high-dose-rate intracavitary brachytherapy and external beam radiotherapy. METHODS AND MATERIALS: Ninety-two patients with uterine cervical carcinoma undergoing definitive radiotherapy alone were retrospectively analyzed. The median follow-up time for all patients was 32 months (range, 13-60 months). The cumulative biologically effective dose (BED) was calculated at the rectal reference point as defined by the International Commission on Radiation Units and Measurements Report 38 (BED(RP)) and at the CTRP (BED(CTRP)). Late rectal complications were recorded according to the Radiation Therapy Oncology Group grading system. RESULTS: The late rectal complications were distributed as follows: Grade 0, 68 patients (74%); Grade 1, 20 patients (22%); Grade 2, 4 patients (4%). Univariate analysis showed that BED(RP), BED(CTRP), RP dose/point A dose ratio, and CTRP dose/point A dose ratio were significantly correlated with late rectal complications (p < 0.05). On multivariate analysis, patients with a rectal BED(CTRP) >/=140 Gy(3) presented with significantly greater frequency of rectal complications (p = 0.031). CONCLUSIONS: The present results suggest that BED(CTRP) is a useful predictive factor for late rectal complications.     

Figo IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy

PURPOSE: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS: The records of 1,096 patients treated with radiation therapy between 1960 and 1993 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. Of these, 983 (90%) were treated with curative intent and 113 were treated only to achieve palliation of symptoms. Of 907 patients who completed the intended curative treatment, 641 (71%) were treated with a combination of external beam irradiation (EBRT) and intracavitary irradiation (ICRT) and 266 (29%) were treated with EBRT only. The median duration of treatment for these 907 patients was 51 days. Between 1966 and 1980, only 52% of patients who completed treatment with curative intent received ICRT, compared with 92% of patients treated during 1981-1993, an increase that reflects an evolution in the philosophy of treatment for advanced tumors. In general, the intensity of ICRT correlated inversely with the dose of EBRT to the,central pelvis. Median follow-up of surviving patients was 134 months. RESULTS: For 983 patients treated with initial curative intent, disease-specific survival (DSS) was significantly worse for those who were < 40 years old, had experienced more than a 10% weight loss, or had a hemoglobin level < 10 g/dl before or during radiation therapy. Tumor factors that correlated with a relatively poor DSS were bilateral pelvic wall involvement, clinical tumor diameter > or = 8 cm, hydronephrosis, lower vaginal involvement, and evidence of lymph node metastases on lymphangiogram (p < 0.01 in all cases). For the 907 patients who completed treatment with curative intent, 641 who had ICRT had a DSS of 45% at 5 years, compared with 24% for those treated with EBRT alone (p < 0.0001). Those who received > 52 Gy of EBRT to the central pelvis had DSS rates of 27-34%, compared with 53% for patients treated with lower doses of EBRT to the central pelvis and more intensive ICRT (p < 0.0001). At 5 years, the actuarial risk of major complications was also greater for patients treated with > 52 Gy of EBRT to the central pelvis (57-68%), compared with those who had 48-52 Gy (28%) and those who had < or = 47 Gy of EBRT to the central pelvis (15%) (p < 0.0001). Outcome was also compared for four time periods during which different treatment policies were in place for patients with Stage IIIB disease. The highest DSS (51%) and lowest actuarial complication rate (17%) were achieved during the most recent period (1981-1993) when modest doses of EBRT were combined with relatively intensive ICRT (p < 0.01 for both comparisons). CONCLUSION: Aggressive use of ICRT, carefully balanced with pelvic EBRT, is necessary to achieve the best ratio between tumor control and complications for patients with FIGO Stage IIIB carcinoma of the cervix. In our experience, the highest DSS rates and the lowest complication rates were achieved with a combination of 40-45 Gy of EBRT combined with ICRT.