ICRU reference dose in an era of intensity-modulated radiation therapy clinical trials: correlation with planning target volume mean dose and suitability for intensity-modulated radiation therapy dose prescription.

BACKGROUND AND PURPOSE: IMRT clinical trials lack dose prescription and specification standards similar to ICRU standards for two- and three-dimensional external beam planning. In this study, we analyzed dose distributions for patients whose treatment plans incorporated IMRT, and compared the dose determined at the ICRU reference point to the PTV doses determined from dose-volume histograms. Additionally, we evaluated if ICRU reference type single-point dose prescriptions are suitable for IMRT dose prescriptions. MATERIALS AND METHODS: For this study, IMRT plans of 117 patients treated at our institution were randomly selected and analyzed. The treatment plans were clinically applied to the following disease sites: abdominal (11), anal (10), brain (11), gynecological (15), head and neck (25), lung (15), male pelvis (10) and prostate (20). The ICRU reference point was located in each treatment plan following ICRU Report 50 guidelines. The reference point was placed in the central part of the PTV and at or near the isocenter. In each case, the dose was calculated and recorded to this point. For each patient--volume and dose (PTV, PTV mean, median and modal) information was extracted from the planned dose-volume histogram. RESULTS: The ICRU reference dose vs PTV mean dose relationship in IMRT exhibited a weak positive association (Pearson correlation coefficient 0.63). In approximately 65% of the cases studied, dose at the ICRU reference point was greater than the corresponding PTV mean dose. The dose difference between ICRU reference and PTV mean doses was 2% in approximately 79% of the cases studied (average 1.21% (+/-1.55), range -4% to +4%). Paired t-test analyses showed that the ICRU reference doses and PTV median doses were statistically similar (p=0.42). The magnitude of PTV did not influence the difference between ICRU reference and PTV mean doses. CONCLUSIONS: The general relationship between ICRU reference and PTV mean doses in IMRT is similar to that in 3D CRT distributions. Point doses in IMRT are influenced by the degree of intensity modulation as well as calculation grid size utilized. Although the ICRU reference point type prescriptions conceptually may be extended for IMRT dose prescriptions and used as a representative of tumor dose, new universally acceptable dose prescription and specification standards for IMRT based on RTOG IMRT prescription model incorporating dose-volume specification would likely lead to greater consistency among treatment centers.

Tolerance of tissue transfers to adjuvant radiation therapy in primary soft tissue sarcoma of the extremity.

PURPOSE: Treatment of extremity sarcomas occasionally requires tissue transfer in the form of pedicle flaps, free flaps, or skin grafts to repair surgical defects. These tissues are often subject to radiation (RT) and are therefore at risk for wound breakdown requiring reoperation. This study reviews a single center's experience with tissue transfer and postoperative RT. METODS AND MATERIALS: Between 1983 and 2000, 43 adult patients (>16 years old) with primary high-grade soft tissue extremity sarcomas underwent limb-sparing surgery and reconstruction of their surgical defects, followed by adjuvant RT. The reconstructions were as follows: pedicle flaps (n = 14), free flaps (n = 10), skin grafts (n = 4), or a combination (n = 15). Postoperative external beam radiation therapy (EBRT) (median dose: 63 Gy) alone was given to 27 patients (63%). Adjuvant brachytherapy (BRT) was given to 16 patients (37%); BRT alone (median dose: 45 Gy) was given to 12 patients and combined with EBRT for 4 patients (EBRT: 45 Gy; BRT: 20 Gy). Comorbid conditions such as diabetes, hypertension, tobacco use, and obesity (calculated using body mass index >or=30) were present in 30 patients (70%). Tumor characteristics were as follows: 26 were >5 cm in size, 37 were deep, and 30 were in the lower extremity. The median follow-up time, calculated from the date of operation, was 32 months. Five of 43 patients suffered wound complications necessitating reoperation; however, 3 patients developed complications before initiation of RT and were therefore excluded from the analysis. Two of 43 patients (5%) required reoperation for wound complications after RT; 1 of these patients ultimately required amputation for necrosis. The 5-year overall wound reoperation rate was 6% (95% confidence interval: 0-14%). The influence of patient and tumor characteristics, as well as the type of RT, on the wound reoperation rates is as follows: BRT vs. EBRT (17% vs. 0%, p = 0.06); upper vs. lower extremity (0% vs. 8%, p = 0.41); 5 cm (8% vs. 4%, p = 0.9); comorbidity vs. no comorbidity (3% vs. 13%, p = 0.8); age 50 (8% vs. 4%, p = 0.8). CONCLUSION: Based on this review, most tissue transfers (95%) tolerated subsequent adjuvant radiation therapy well. Although more wound complications necessitating reoperation were seen in patients who received BRT, whether this is because of the inherent susceptibility of flaps and skin grafts to breakdown in the immediate postoperative period vs. the direct result of BRT needs further investigation.

Postmastectomy CT-based electron beam radiotherapy: dosimetry, efficacy, and toxicity in 118 patients.

PURPOSE: To evaluate the technique, dosimetry, acute and late toxicity, local control (LC), and overall survival (OS) with the use of computed tomography (CT)-based postmastectomy electron beam therapy (PMEBT) in high-risk patients. METHODS AND MATERIALS: From 1990 to 2000, 118 patients with pathologic stage I-IIIB breast cancer underwent PMEBT of the chest wall (CW) (n = 3), CW and supraclavicular fossa (SCV) (n = 63), CW, SCV, and internal mammary lymph nodes (IMN) (n = 51), and SCV+IMN (n = 1). Radiation therapy was delivered with an en face electron beam with a custom cutout. Treatment plans were all CT-based. The plans of 16 patients were retrospectively reviewed to analyze dosimetry data. A retrospective chart review was conducted to assess acute and late complications, LC, and OS. RESULTS: At a median follow-up of 43 months, 5-year LC and OS were 91% and 61%, respectively. Sixty-one patients developed acute grade 3-4 skin toxicity, necessitating treatment breaks in 33 patients. Fifteen patients experienced a worsening of lymphedema, and 2 patients developed cardiac injury thought to be unrelated to radiotherapy. No patients developed symptomatic pneumonitis. Dosimetric analysis revealed heart and lung normal tissue complication probabilities of zero. Analysis of other clinically relevant dosimetric parameters revealed PMEBT to be comparable to previously reported techniques. CONCLUSION: Postmastectomy electron beam therapy is an effective way to deliver radiation to the postmastectomy chest wall and adjacent nodal sites. It offers acceptable acute and late toxicities and a high degree of local control given the high-risk population to which it is offered.

Hypofractionated whole-breast radiation therapy: does breast size matter?

PURPOSE: To evaluate the effects of breast size on dose-volume histogram parameters and clinical toxicity in whole-breast hypofractionated radiation therapy using intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: In this retrospective study, all patients undergoing breast-conserving therapy between 2005 and 2009 were screened, and qualifying consecutive patients were included in 1 of 2 cohorts: large-breasted patients (chest wall separation>25 cm or planning target volume [PTV]>1500 cm3) (n=97) and small-breasted patients (chest wall separation<25 cm and PTV<1500 cm3) (n=32). All patients were treated prone or supine with hypofractionated IMRT to the whole breast (42.4 Gy in 16 fractions) followed by a boost dose (9.6 Gy in 4 fractions). Dosimetric and clinical toxicity data were collected and analyzed using the R statistical package (version 2.12). RESULTS: The mean PTV V95 (percentage of volume receiving>=95% of prescribed dose) was 90.18% and the mean V105 percentage of volume receiving>=105% of prescribed dose was 3.55% with no dose greater than 107%. PTV dose was independent of breast size, whereas heart dose and maximum point dose to skin correlated with increasing breast size. Lung dose was markedly decreased in prone compared with supine treatments. Radiation Therapy Oncology Group grade 0, 1, and 2 skin toxicities were noted acutely in 6%, 69%, and 25% of patients, respectively, and at later follow-up (>3 months) in 43%, 57%, and 0% of patients, respectively. Large breast size contributed to increased acute grade 2 toxicity (28% vs 12%, P=.008). CONCLUSIONS: Adequate PTV coverage with acceptable hot spots and excellent sparing of organs at risk was achieved by use of IMRT regardless of treatment position and breast size. Although increasing breast size leads to increased heart dose and maximum skin dose, heart dose remained within our institutional constraints and the incidence of overall skin toxicity was comparable to that reported in the literature. Taken together, these data suggest that hypofractionated radiation therapy using IMRT is a viable and appropriate therapeutic modality in large-breasted patients.

Change in seroma volume during whole-breast radiation therapy.

PURPOSE: After breast-conserving surgery, a seroma often forms in the surgical cavity. If not drained, it may affect the volume of tumor bed requiring a boost after whole-breast radiation therapy (WBRT). Our objective was to evaluate the change in seroma volume that occurs during WBRT, before boost planning. METHODS AND MATERIALS: A retrospective review was performed of women receiving breast-conserving therapy with evidence of seroma at the time of WBRT planning. Computed tomography (CT) simulation was performed before WBRT and before the tumor bed boost. All patients received either a hypofractionated (42.4 Gy/16 fraction + 9.6 Gy/4 fraction boost) or standard fractionated (50.4 Gy/28 fraction + 10 Gy/5 fraction boost) regimen. Seroma volumes were contoured and compared on CT at the time of WBRT simulation and tumor bed boost planning. RESULTS: Twenty-four patients with evidence of seroma were identified and all patients received WBRT without drainage of the seroma. Mean seroma volume before WBRT and at boost planning were significantly different at 65.7 cm(3) (SD, 50.5 cm(3)) and 35.6 cm(3) (SD, 24.8 cm(3)), respectively (p < 0.001). Mean and median reduction in seroma volume during radiation were 39.6% (SD, 23.8%) and 46.2% (range, 10.7-76.7%), respectively. Fractionation schedule was not correlated with change in seroma volume. Length of time from surgery to start of radiation therapy showed an inverse correlation with change in seroma volume (Pearson correlation r = -0.53, p < 0.01). CONCLUSIONS: The volume of seroma changes significantly during WBRT. Consequently, the accuracy of breast boost planning is likely affected, as is the volume of normal breast tissue irradiated. CT-based boost planning before boost irradiation is suggested to ensure appropriate coverage.

Long-term outcomes in extremity soft tissue sarcoma after a pathologically negative re-resection and without radiotherapy.

BACKGROUND: The purpose was to define the rate of local recurrence (LR) and identify prognostic factors for LR in patients with extremity soft-tissue sarcoma (STS) treated with limb-sparing surgery and a pathologically negative re-resection specimen without radiotherapy (RT). METHODS: A review of the prospective sarcoma database identified 200 patients with primary, nonmetastatic, extremity STS treated with limb-sparing surgery between June 1982 and December 2002 who had a pathologically confirmed negative re-resection. None of the patients had adjuvant RT. Univariate and multivariate analyses were performed to determine clinicopathologic factors associated with LR. RESULTS: With a median follow-up of 82 months the 5-year actuarial LR rate was 9%. Factors associated with higher LR rates on univariate and multivariate analysis were older age, stage III presentation, and histology. The 5-year LR rate was 5% for those<50 compared with 15% for those>or=50 (P=.001). For patients with stage III the LR rate was 26% versus 7% for those with stage I/II (P<.001). On multivariate analysis only age>or=50 (relative risk [RR] 3.3; P=.02) and stage III disease (RR 3.4; P=.01) remained significant predictors for LR. When the cohort of patients was divided into 3 groups based on the number of risk factors present, the 5-year LRs were as follows: no risk factors (stage I/II and<50 years old) 4%, 1 risk factor (stage III or>or=50) 12%, and 2 risk factors (stage III and>or=50) 31% (P<.01). CONCLUSIONS: Patients with a pathologically negative re-excision represent a heterogeneous group. Whereas the overall rate of local recurrence at 5 years was 9% for the entire cohort, patients with older age and/or stage III disease had a higher rate of LR. Therefore, treatment decisions especially with regard to adjuvant RT should be individualized and not be based solely on the finding of a negative re-resection.