Three-dimensional External Beam Research Articles

Identifying Patients Who Are Unsuitable for Accelerated Partial Breast Irradiation Using Three-dimensional External Beam Conformal Techniques

Several recent studies reported that severe late toxicities including soft-tissue fibrosis and fat necrosis are present in patients treated with accelerated partial breast irradiation (APBI) and that these toxicities are associated with the large volume of tissue targeted by high-dose irradiation. The present study was performed to clarify which patients are unsuitable for APBI to avoid late severe toxicities. Study subjects comprised 50 consecutive patients with Stage 0-II unilateral breast cancer who underwent breast-conserving surgery, and in whom five or six surgical clips were placed during surgery. All patients were subsequently replanned using three-dimensional conformal radiotherapy (3D-CRT) APBI techniques according to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 and Radiation Therapy Oncology Group (RTOG) 0413 protocol. The beam arrangements included mainly noncoplanar four- or five-field beams using 6-MV photons alone. Dose-volume histogram (DVH) constraints for normal tissues according to the NSABP/RTOG protocol were satisfied in 39 patients (78%). Multivariate analysis revealed that only long craniocaudal clip distance (CCD) was correlated with nonoptimal DVH constraints (p = 0.02), but that pathological T stage, anteroposterior clip distance (APD), site of ipsilateral breast (IB) (right/left), location of the tumor (medial/lateral), and IB reference volume were not. DVH constraints were satisfied in 20% of patients with a long CCD (≥5.5 cm) and 92% of those with a short CCD (p < 0.0001). Median IB reference volume receiving ≥50% of the prescribed dose (IB-V(50)) of all patients was 49.0% (range, 31.4-68.6). Multivariate analysis revealed that only a long CCD was correlated with large IB-V(50) (p < 0.0001), but other factors were not. Patients with long CCDs (≥5.5 cm) might be unsuitable for 3D-CRT APBI because of nonoptimal DVH constraints and large IB-V(50).

Three‐dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture

Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown. From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992-2004 were identified. By using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall-related fracture outside the radiation field. After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38-2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56-1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88-3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17-1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97-2.10). The number needed to treat to result in 1 hip fracture during a 10-year period was 51 patients (95% CI, 31-103). In men with prostate cancer, pelvic 3-D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT must be site-specific as there was no increase in the risk of fall-related fractures in bones that were outside the radiation field.

Therapeutic efficacy of three-dimensional conformal radiotherapy combined with concurrent weekly cisplatin-based chemotherapy for locally advanced cervical cancer

Objective To analyze the therapeutic efficacy and treatment related toxicities for patients with locally advanced cervical cancer treated with three-dimensional conformal radiotherapy (3DCRT) combined with concurrent chemotherapy. Methods From January 2007 to February 2008, 181 patients with stage ⅡA-ⅣA cervical cancer were retrospectively analyzed. All patients were treated with CT-based three-dimensional external beam and 192Ir intracavity radiotherapy combined with concurrent weekly cisplatin-based chemotherapy. The median age was 50 years (range, 32 to 82 years). The overall survival ( OS), disease-free survival (DFS) and local control (LC) rates were calcalated by Kaplan-Meier method and the difference was compared using Log-rank test. The treatment related toxicities were evaluated according to Radiotherapy Oncology Group (RTOG) criteria. Results With a median follow-up time of 34 months and following rate of 92. 2%, the 3-year OS, DFS and LC rates were 73.4%, 70. 4% and 91.3%,respectively. The 3-year OS rate was 66. 9% for patients with tumor diameter ≥4 cm and 86. 4% for those with tumor diameter ＜4 cm( χ2 =6. 29 ,P =0. 012). The incidences of grade 1 and grade 2 acute toxicities of the lower gastrointestinal tract and the genitourinary system were 40. 0% ,45.0% and 19. 9% ,4. 4%,retrospectively. There were no grade 3 or more acute toxicities. The incidence of grades 3 or 4 late toxicities of the lower gastrointestinal tract was 4. 9%. Conclusions CT-based three-dimensional external beam and 192Ir intracavity radiotherapy combined with concurrent chemotherapy can achieve good therapeutic effects for locally advanced cervical cancer. The acute and late toxicities are significantly reduced compared with historic controls as a result of incorporation of 3DCRT technique. Key words: Cervical neoplasms/radiochemotherapy; Radiotherapy,three-dimensional conformal; Chemotherapy,concurrent; Prognosis

Comment by J. Schäfer, G. Welzel, F. Wenz on D. Norkus et al. A Randomized Trial Comparing Hypofractionated and Conventionally Fractionated Three-Dimensional External-Beam Radiotherapy for Localized Prostate Adenocarcinoma. A Report on Acute Toxicity

Comment by J. Schäfer, G. Welzel, F. Wenz on D. Norkus et al. A Randomized Trial Comparing Hypofractionated and Conventionally Fractionated Three-Dimensional External-Beam Radiotherapy for Localized Prostate Adenocarcinoma. A Report on Acute Toxicity

Does Three-Dimensional External Beam Partial Breast Irradiation Spare Lung Tissue Compared With Standard Whole Breast Irradiation?

To determine whether three-dimensional conformal partial breast irradiation (3D-PBI) spares lung tissue compared with whole breast irradiation (WBI) and to include the biologically equivalent dose (BED) to account for differences in fractionation. Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients randomized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville, Florida. WBI plans were for 50 Gy in 25 fractions, and 3D-PBI plans were for 38.5 Gy in 10 fractions. Volume of ipsilateral lung receiving 2.5, 5, 10, and 20 Gy was recorded for each plan. The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans. Ipsilateral mean lung dose was recorded for each plan and converted to BED. There was a significant decrease in volume of lung receiving 20 Gy with PBI (median, 4.4% vs. 7.5%; p < 0.001), which remained after correction for fractionation (median, 5.6% vs. 7.5%; p = 0.02). Mean lung dose was lower for PBI (median, 3.46 Gy vs. 4.57 Gy; p = 0.005), although this difference lost significance after conversion to BED (median, 3.86 Gy(3) vs 4.85 Gy(3), p = 0.07). PBI plans exposed more lung to 2.5 and 5 Gy. 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI.

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.

Partial-Breast Radiation for Early Staged Breast Cancers: Hypothesis, Existing Data, and a Planned Phase III Trial

This review of clinical data from partial-breast treatment studies discusses results from a single institution's experience using brachytherapy catheters, the MammoSite balloon (Proxima Company, Alpharetta, GA), and three-dimensional external beam partial-breast treatment. Rationale, techniques, dose schedules, and available results are presented. Intra-operative single-dose radiation to the lumpectomy site is also reviewed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) and Radiation Therapy Oncology Group (RTOG) cooperative groups are opening a phase III trial to compare partial-breast treatment to the standard 5- to 6-week course of whole-breast radiation. The design of this study is also presented in this review.

Accelerated partial breast irradiation: technically feasible but who will benefit?

Modern breast cancer radiotherapy aims to increase uncomplicated cure rates. A priority is reduction of late effects which include chronic chest wall or breast pain, poor cosmesis, and cardiac toxicity. As breast screening detects early cancers we may be able to safely restrict irradiation postlumpectomy to the tumour bed with a margin, defining a 'partial breast' target volume for treatment. Differing technical approaches to partial breast irradiation are being evaluated in phase III studies with standard whole breast irradiation. These include intra-operative single doses, hypo-fractionated accelerated brachytherapy, and LINAC (linear accelerator)-based three-dimensional external beam therapy.

Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer •

Purpose: Standard therapies for locally advanced prostate cancer have resulted in suboptimal disease control rates. A Phase I/II trial was designed for patients with positive seminal vesicle biopsies, prostate-specific antigen (PSA) >15 ng/ml, Gleason score ⩾8, or clinical classification T2c–T3 to improve local control and to test the tolerance of the prostate to high-dose radiation by using neoadjuvant hormonal therapy, 103Pd brachytherapy, and conformal three-dimensional external beam radiation therapy (EBRT). This article outlines treatment-related morbidity and PSA response to this regimen and analyzes the effect of escalating doses of brachytherapy. Methods and Materials: Forth-three patients with T1c–T3 prostate cancer were enrolled in a Phase I/II trial from March 1994 through September 1997. Follow-up ranged from 12 to 64 months (median, 32 months). Pretreatment PSA ranged from 2.1 to 202 ng/ml (median, 16 ng/ml). Seventy-seven percent (33 of 43) of patients had high-grade tumors (score ⩾7). Seventy-four percent (32 of 43) had stage ⩾T2c. A total of 21 (49%) patients had positive seminal vesicle biopsies. Treatment consisted of hormonal therapy for 3 months with leuprolide and flutamide followed by a 103Pd implant and, 2 months later, 59.4 Gy of three-dimensional EBRT. Hormonal therapy was continued for 9 months. The planned 103Pd dose was escalated from 57 Gy (13 patients) to 77 Gy (13 patients) to 86 Gy (17 patients). Results: The actuarial freedom from PSA failure (PSA > 0.5 ng/ml) at 4 years was 74%. There were no significant differences found when analyzing patients by presenting PSA or seminal vesicle status. There was a trend toward improved outcome with higher doses delivered to the prostate via the implant. Patients receiving doses ⩾65 Gy (31 patients) had a freedom from PSA failure rate at 4 years of 89.5%, compared with 52.5% for those receiving doses <65 Gy (10 patients; p = 0.08). The last PSA values for those patients free from PSA failure were ⩽0.1 ng/ml in 25 (69%), >0.1–0.2 ng/ml in 5 (14%), and >0.2–0.5 ng/ml in 6 (17%). The actuarial freedom from developing Grade 2 proctitis was 75% at 4 years. There was a trend toward increased proctitis with increasing prostate implant doses. Patients with doses ⩽70 Gy ( n = 12) had a 92% freedom from Grade 2 proctitis compared with 67.5% for those with doses delivered to 90% of the gland from a dose–volume histogram of >70 Gy ( n = 29) ( p = 0.15). There were no cases of Grade 3 or 4 proctitis. The 3-year actuarial preservation of sexual potency rate was 43%. Conclusions: The preliminary results from this regimen show an improvement in PSA control for this group of locally advanced prostate cancer patients over more standard therapies. To maximize control while minimizing toxicity, doses of 65–70 Gy of 103Pd should be used when 59.4 Gy of three-dimensional EBRT is delivered. Longer follow-up will be needed to further substantiate these findings.

Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation

Purpose: This retrospective study compares the long-term biochemical disease-free survival for patients undergoing radical prostatectomy, transperineal ultrasound-guided 125Iodine implantation, or external beam irradiation alone in a tertiary referral community-based hospital. Methods and Materials: Five hundred forty patients were available for evaluation, which included: external beam, 132; 125I, 186; and radical prostatectomy, 222. For the 318 patients referred to the Department of Radiation Oncology, those with T3 disease underwent external beam irradiation while patients with T1 or T2 underwent 125I implantation or external beam irradiation as definitive treatment. No patient received androgen ablation. Patients undergoing irradiation were considered a biochemical failure if their PSA nadir was > 1 at 1 year or, if following a nadir PSA < 1, the patient subsequently experienced three consecutive rising PSA values obtained at a minimum 3-month interval. Patients undergoing prostatectomy were considered a biochemical failure if their postop PSA remained detectable > 0.2 ng/mL or if they had three consecutive increases in their PSA or an increase in their postoperative PSA warranting intervention with androgen ablation or external beam irradiation to the pelvis. Results: Patients were stratified by pretreatment risk groups predicting for post-treatment PSA recurrence. Patients were considered to be at a low or intermediate risk for recurrence if their clinical stage was T1c, T2a, T2b, pretreatment PSA level was ≤ 20, or their biopsy Gleason score was ≤ 6. Patients were considered to be at high risk for failure if they were clinically stage T2c, T3, PSA at diagnosis > 20, or Gleason score was ≥ 7. For 132 patients undergoing external beam irradiation, 28 of 37 low or intermediate risk obtained a 1 year nadir PSA of < 1 (76%) while 40% of high risk patients obtained nadir < 1. Of 186 patients undergoing 125I, 112 of 147 low or intermediate risk (76%) obtained a nadir PSA < 1. Twenty of 39 (51%) high risk obtained a nadir PSA < 1. Of the 222 patients undergoing prostatectomy, 83 of 88 (94%) low or intermediate risk had undetectable levels of PSA at 1 year. One hundred seventeen of 134 (86%) were high risk and had undetectable levels of PSA at 1 year. The biochemical disease-free survival for patients with low or intermediate risk at 5 years is approximately 70% with no significant difference between those patients treated with radical prostatectomy, external beam, or 125I. For those patients with high risk factors for recurrence, there is no significant difference between ultrasound-guided implant or external beam, but there is a significant improvement in biochemical disease-free survival with radical prostatectomy. Conclusion: For patients with low or intermediate risk disease, external beam, ultrasound-guided 125I, or a radical prostatectomy give comparable long-term biochemical disease-free survival. For patients with high risk disease, a radical prostatectomy provides a significantly improved biochemical disease-free survival. Our current protocols utilize androgen ablation in combination with conformal three-dimensional external beam irradiation or androgen ablation in conjunction with external beam irradiation and 103Pd seed implantation for patients at high risk for extra capsular disease. It is too early to determine if this combination therapy will give results comparable to radical prostatectomy. For patients who obtain a 1 year nadir PSA of < 1, the biochemical disease-free survival is durable with little risk of subsequent recurrence.

Conformai external beam treatment of prostate cancer

Objectives This study reports the 5-year outcomes of treatment for patients with prostate cancer treated largely with conformal three-dimensional radiation therapy. Methods Results are presented for 456 consecutive patients treated prior to December 31, 1993 whose pretreatment prostate-specific antigen (PSA) levels are known. Biochemical failure was defined as two consecutive rises in the PSA that equals or exceeds 1.5 ng/mL. Kaplan-Meier product limit methods, the logrank test, and Cox regression models were used in evaluating the data. No patient was lost to follow-up. Results The 5-year biochemically free of failure (bNED) rate for all patients was 61% and 57% at 7 years. In the group with pretreatment PSA less than 10 ng/mL, the 5-year bNED rate for patients with localized disease (T1,2AB disease, Gleason sum of 6 or less) was 85% and for those with locally advanced disease (T2C,3), 70%. In the group with pretreatment PSA of 10 to 19.9 ng/mL, the 5-year bNED rate for patients with localized disease was 66% and for those with locally advanced disease, 44%. In the group with pretreatment PSA of 20 ng/mL or above, the patients with localized or locally advanced disease had 5-year bNED rates of 31% and 21%, respectively. Conclusions The results of largely conformal three-dimensional external beam treatment of localized prostate cancer produced 5-year bNED results that are comparable to recent reports of nerve-sparing prostatectomy. Preliminary 7-year bNED results in all patients and in patients with localized tumors indicated a modest decrease in the cancer-free rate from that observed at 5 years, suggesting the results are durable.

Intersection of shaped radiation beams with arbitrary image sections

Display of the intersection of a shaped radiation beam with an arbitrarily oriented image plane is a very useful tool in three-dimensional external beam radiation treatment planning. Coverage of the tumor (or target) region can be graphically investigated, as well as the radiation received by the surrounding healthy tissues. An algorithm is presented that obtains and displays these intersections by projecting contour points defining the beam's aperture on the plane. A general procedure is given, as well as provisions for special cases in which a straightforward projection is not sufficient.