Intensity-Modulated Radiation Therapy for Breast Cancer

Over the past 2 decades, numerous advances and innovations have occurred in all technical aspects of radiation therapy (RT), including three-dimensional (3D) treatment planning, conformal radiation delivery, intensity-modulated radiation therapy (IMRT), patient immobilization, and precise treatment verification. Despite incredible progress on all fronts, standard RT for breast cancer has changed very little and has not fully exploited many of the advances commonly used to treat most other malignancies. Increasing data have also accumulated, indicating that dose non-uniformities within the breast with traditional RT techniques can be greater than in many other anatomic sites. These significant dose inhomogeneities can produce unnecessary acute and chronic toxicities as well as unacceptable long-term cosmetic results. In addition, the lack of accurate verification of target volume coverage (e.g. lumpectomy cavity or chest wall) may result in diminished tumor control. In this review, we demonstrate how 3D treatment planning combined with IMRT using our in-house step and shoot, multi-leaf collimator (sMLC) technique for tangential whole-breast RT can be an efficient and reliable method for achieving a more uniform dose throughout the whole breast. Strict dose-volume constraints can be readily met in the majority of patients, resulting in both improved coverage of breast tissue as well as a potential reduction in acute and chronic toxicities. Since the median number of sMLC segments required per patient is only eight, treatment time is not significantly increased. As a result, widespread implementation of this technology can be achieved for most patients with breast cancer with minimal imposition on clinic resources and time constraints. In addition, since lung and heart volumes are also identified, doses to these structures can be maintained at predefined ‘safe’ levels by the treating physician. With the increased use of potentially cardiotoxic drugs in a substantial number of patients with breast cancer, the use of RT in these patients will take on greater significance. It remains to be seen whether the previously noted improvements in survival of patients with postmastectomy RT can be maintained using ‘standard’ techniques combined with these cardiotoxic drugs or whether more technologically sophisticated RT approaches (e.g. IMRT) will be required.     

Intensity modulation to improve dose uniformity with tangential breast radiotherapy: initial clinical experience

Purpose: We present a new technique to improve dose uniformity and potentially reduce acute toxicity with tangential whole-breast radiotherapy (RT) using intensity-modulated radiation therapy (IMRT). The technique of multiple static multileaf collimator (sMLC) segments was used to facilitate IMRT.

Methods and Materials: Ten patients with early-stage breast cancer underwent treatment planning for whole-breast RT using a new method of IMRT. The three-dimensional (3D) dose distribution was first calculated for equally weighted, open tangential fields (i.e., no blocks, no wedges). Dose calculation was corrected for density effects with the pencil-beam superposition algorithm. Separate MLC segments were constructed to conform to the beam’s-eye-view projections of the 3D isodose surfaces in 5% increments, ranging from the 120% to 100% isodose surface. Medial and lateral MLC segments that conformed to the lung tissue in the fields were added to reduce transmission. Using the beam-weight optimization utility of the 3D treatment planning system, the sMLC segment weights were then determined to deliver the most uniform dose to 100 reference points that were uniformly distributed throughout the breast. The accuracy of the dose calculation and resultant IMRT delivery was verified with film dosimetry performed on an anthropomorphic phantom. For each patient, the dosimetric uniformity within the breast tissue was evaluated for IMRT and two other treatment techniques. The first technique modeled conventional practice where wedges were derived manually without consideration of inhomogeneity effects (or density correction). A recalculation was performed with density correction to represent the actual dose delivered. In the second technique, the wedges were optimized using the same beam-weight optimization utility as the IMRT plan and included density correction. All dose calculations were based on the pencil-beam superposition algorithm.

Results: For the sMLC technique, treatment planning required approximately 60 min. Treatment delivery (including patient setup) required approximately 8–10 min. Film dosimetry measurements performed on an anthropomorphic phantom generally agreed with calculations to within ± 3%. Compared to the wedge techniques, IMRT with sMLC segments resulted in smaller “hot spots” and a lower maximum dose, while maintaining similar coverage of the treatment volume. A median of only 0.1% of the treatment volume received ≥ 110% of the prescribed dose when using IMRT versus 10% with standard wedges. A total of 6–8 segments were required with the majority of the dose delivered via the open segments. The addition of the lung-block segments to IMRT was of significant benefit for patients with a greater proportion of lung parenchyma within the irradiated volume. Since August 1999, 32 patients have been treated in the clinic with the IMRT technique. No patient experienced RTOG grade III or greater acute skin toxicity.

Conclusion: The use of intensity modulation with an sMLC technique for tangential breast RT is an efficient and effective method for achieving uniform dose throughout the breast. It is dosimetrically superior to the treatment techniques that employ only wedges. Preliminary findings reveal minimal or no acute skin reactions for patients with various breast sizes.     

High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients

To report the acute and late toxicity and preliminary biochemical outcomes in 772 patients with clinically localized prostate cancer treated with high-dose intensity-modulated radiotherapy (IMRT).

Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. Treatment was planned using an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. A total of 698 patients (90%) were treated to 81.0 Gy, and 74 patients (10%) were treated to 86.4 Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined according to The American Society of Therapeutic Radiation Oncology Consensus Statement. The median follow-up time was 24 months (range: 6–60 months).

Thirty-five patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3). Eleven patients (1.5%) developed late Grade 2 rectal bleeding. Four patients (0.1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 3-year actuarial likelihood of ≥ late Grade 2 rectal toxicity was 4%. Seventy-two patients (9%) experienced late Grade 2 urinary toxicity, and five (0.5%) developed Grade 3 urinary toxicity (urethral stricture). The 3-year actuarial likelihood of ≥ late Grade 2 urinary toxicity was 15%. The 3-year actuarial PSA relapse-free survival rates for favorable, intermediate, and unfavorable risk group patients were 92%, 86%, and 81%, respectively.

These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be significantly reduced compared with what has been observed with conventional three-dimensional conformal radiotherapy techniques. Short-term PSA control rates seem to be at least comparable to those achieved with three-dimensional conformal radiotherapy at similar dose levels. Based on this favorable risk:benefit ratio, IMRT has become the standard mode of conformal treatment delivery for localized prostate cancer at our institution.     

Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer

: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer.

: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74–78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24–102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity.

: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p <0.0001 for all comparisons), the absolute rectal volume appeared to be a factor only at the higher doses of 70, 75.6, and 78 Gy (p = 0.0514, 0.0016, and 0.0021, respectively). The following variables also correlated with toxicity on the univariate analysis: maximal dose to the clinical target volume, maximal dose to rectum, maximal dose to the rectum as a percentage of the prescribed dose, and maximal dose delivered to 10 cm³ of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p = 0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p <0.05 for all comparisons).

: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications. Therefore, dose escalation may be safely achieved by adherence to dose-volume histogram constraints during treatment planning and organ localization at the time of treatment to ensure consistent patient setup.     

Phase II study of high central dose Gamma Knife radiosurgery and marimastat in patients with recurrent malignant glioma

: To assess the outcome of high central dose Gamma Knife radiosurgery plus marimastat in patients with recurrent malignant glioma.

: Twenty-six patients with recurrent malignant glioma were enrolled in a prospective Phase II study between November 1996 and January 1999. The radiosurgery dose was prescribed at the 25–30% isodose surface to increase the dose substantially within the tumor’s presumably hypoxic core. Marimastat was administered after radiosurgery to restrict regional tumor progression. Survival was compared with that of historical patients treated at our institution with standard radiosurgery.

: The median times to progression after radiosurgery for Grade 3 and 4 patients was 31 and 15 weeks, respectively. The corresponding median survival time after radiosurgery was 68 and 38 weeks. The median survival time after radiosurgery in the historical patients was 59 and 44 weeks.

: The dual strategies of using high central dose radiosurgery to overcome tumor hypoxia together with marimastat to inhibit local tumor invasion may offer a small survival advantage for recurrent Grade 3 tumors; they do not offer an advantage for recurrent Grade 4 tumors.     

早期乳腺癌保乳术后全乳调强放射治疗与常规切线野放疗的剂量学比较

目的探讨早期乳腺癌保乳术后全乳调强放射治疗(intensity-modulated radiotherapy,IMRT)的剂量学优势。方法选择6例接受保乳手术的T1N0M0早期乳腺癌病例,其中左侧乳腺癌4例,右侧乳腺癌2例,应用三维调强治疗计划系统为每例患者设计常规切线野与IMRT2种全乳放射治疗计划,处方剂量均为50Gy/25次。用剂量体积直方图(dose volume histograms,DVH)来比较2种计划中计划靶体积(planning target volume,PTV)、危及器官(organs at risks,OARs)的剂量学差异。结果在2种计划中,95%PTV均接受50Gy,99%PTV均接受95%的处方剂量;但在IMRT计划组V110%(接受大于110%处方剂量体积占PTV的百分比)下降了9.1%(46.3%比37.2%,P<0.05);同侧肺的V20(至少接受20Gy照射的肺体积占同侧肺体积的百分比)下降了7.2%(26.8%比18.0%,P<0.05);同侧肺的V30下降了12.0%(23.2%比11.2%,P<0.05);4例左侧乳腺癌患者的心脏V30下降了3.8%(7.0%比3.2%,P<0.05)。结论全乳IMRT在保证靶区覆盖率的前提下,改善了靶区内剂量的均匀性,降低了危及器官的受照剂量及缩小了危及器官的照射体积,尤其是同侧肺、心脏的照射体积,降低放射性肺炎及心血管事件发生的可能。     

乳腺癌保乳术后调强放疗与常规放疗的剂量学比较

 目的　探讨早期乳腺癌保乳术后全乳适形调强放射治疗（IMRT）的剂量学优势。方法　选择10例接受保乳手术的Tis~2N0M0早期乳腺癌病例,其中左侧乳腺癌6例,右侧乳腺癌4例,应用三维治疗计划系统（3D-TPS）为每位患者设计两种全乳放射治疗计划,即切线野常规计划与IMRT计划,处方剂量均为50 Gy／25次。用剂量体积直方图（DVH）来比较两种计划中计划靶体积（PTV）、危及器官（OARS）的剂量学差异。结果　靶区覆盖率在两种计划中相似,分别为97.83 %、97.61 %,与常规计划相比IMRT计划的PTV接受＜95 %处方剂量与＞103 %处方剂量的体积百分比之和（IHI） 从25.42 %减少到2.71 %,PTV接受至少105 %处方剂量照射的体积百分比（V105 %）从25.79 %减少到1.08 %,IMRT计划改善IHI和减少V105 %的平均值,在PTV较大的患者中更明显。左侧乳腺癌患者心脏的平均剂量（Dmean）从6.72 Gy减少到4.95 Gy、心脏接受30 Gy照射的体积百分比（V30）从7.23 %减少到1.04 %。所有患者同侧肺的Dmean从9.19 Gy减少到7.65 Gy、至少接受20 Gy 照射的体积百分比（V20）从22.34 %减少到20.18 %。对侧乳腺Dmean从5.12 Gy减少到3.52 Gy,对侧肺Dmean从2.76 Gy减少到1.79 Gy。右侧患者肝脏Dmean从7.23 Gy减少到1.04 Gy。结论　全乳IMRT的剂量学优势主要是在保证靶区覆盖率的前提下,显著改善了靶区剂量分布的均匀性,并在一定程度上降低OARS的受照剂量与容积,乳房体积大的病例可以通过IMRT获得更好的剂量学结果。     

Early-stage bilateral breast cancer treated with breast-conserving surgery and definitive irradiation: The university of pennsylvania experience

: To determine whether patients with early-stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complications, and cosmesis.

: During the period 1977–1992, 55 women with State 0, I, or II concurrent (n = 12) or sequential (n = 43) bilateral breast cancer were treated with definitive irradiation following breast-conserving surgery. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, pathologic axillary lymph node status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival, local control, and regional control were determined. Cosmetic outcome, complication rates, and matching technique were analyzed. The median total radiation dose delivered was 64 Gy *range 42–72) using tangential whole-breast irradiation followed by an electron or iridium implant boost. The tangential fields were matched with no overlap in 40 patients (73%); there was overlap on skin of up to 4 cm in 14 patients. (25%); and the matching technique was unknown in 1 patient (2%). The median follow-up for the 12 women with concurrent bilateral breast cancer was 4.0 years. The median follow-up for the other 43 women with sequential cancer was 9.3 and 4.9 years, respectively, after the first and second cancers.

: For the overall group of 55 patients, the 5- and 10-year overall survival rates were 96% and 94%, respectively, after treatment of the first cancer, and 96% and 92%, respectively, after treatment of the second cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and 75%, respectively, after treatment of the first cancer, and 83% and 72%, respectively, after treatment of the second cancer. For the 110 treated breast cancers, th 5- and 10-year actuarial local failure rates were 5% and 15%, respectively. Complication rates were: 28% breast edema, 8% arm edema, 4% pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no patients developed matchline fibrosis. For patients with a minimum of 3 years of relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104 treated beasts was 85%.

: Definitive irradiation after breast-consercing surgery is technically feasible for selected patients with concurrent or sequential early-stage bilateral breast cancer. Survival, local control, complication rates, and cosmetic outcomes appear comparable to historical reports of breast conservation treatment for unilateral disease. Bilateral definitive breast irradiation after breast-conservation surgery should be considered an acceptable alternative treatment to bilatera; mastectomy for selected patients with concurrent or sequential early-stage bilateral breast cancer.     

Intensity-modulated radiation therapy (IMRT) for meningioma

To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma.

Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method.

Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy.

IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT.     

Dosimetric analysis of a simplified intensity modulation technique for prone breast radiotherapy

PURPOSE: Prone-position breast radiotherapy (RT) has been described as an alternative technique to improve dose homogeneity for women with large, pendulous breasts. We report the feasibility and dosimetric analysis of a simplified intensity-modulated RT (IMRT) technique, previously reported for women in the supine treatment position, to plan prone-position RT to the intact breast. METHODS AND MATERIALS: Twenty patients with clinical Stage TisN0-T1bN1 breast cancer undergoing breast-conserving therapy underwent whole breast RT using a prone position technique. The treatment plans were developed using both conventional tangents and a simplified intensity-modulated tangential beam technique based on optimization of the intensity distributions across the breast. The plans were compared with regard to the dose-volume parameters. RESULTS: Dose heterogeneity within the breast planning target volume was significantly greater for the conventional tangent plans. Of 20 patients, 16 (80%) received maximal doses of > or =110% using the conventional tangents vs. only 1 (5%) using the IMRT plan. The isodose level encompassing 5% of the planning target volume was reduced from an average of 110% with conventional tangents to 105% with IMRT. The maximal dose within the planning target volume was reduced from an average of 114% with conventional tangents to 107% with IMRT. The greatest improvement was seen in the patients with the most pendulous breasts. CONCLUSION: An IMRT planning approach is feasible for prone-position breast RT and improves dose homogeneity, particularly in women with larger, pendulous breasts. Additional follow-up is necessary to determine whether the improvements in dose homogeneity impact acute toxicity and cosmetic outcome in this cohort of women who have historically suffered from poor cosmesis after breast-conserving therapy.     

Tumor antivascular effects of radiotherapy combined with combretastatin a4 phosphate in human non-small-cell lung cancer

PURPOSE: We have previously demonstrated that intensity-modulated radiotherapy (IMRT) with a static multileaf collimator process results in a more homogenous dose distribution compared with conventional wedge-based whole breast irradiation (WBI). In the present analysis, we reviewed the acute and chronic toxicity of this IMRT approach compared with conventional wedge-based treatment. METHODS AND MATERIALS: A total of 172 patients with Stage 0-IIB breast cancer were treated with lumpectomy followed by WBI. All patients underwent treatment planning computed tomography and received WBI (median dose, 45 Gy) followed by a boost to 61 Gy. Of the 172 patients, 93 (54%) were treated with IMRT, and the 79 patients (46%) treated with wedge-based RT in a consecutive fashion immediately before this cohort served as the control group. The median follow-up was 4.7 years. RESULTS: A significant reduction in acute Grade 2 or worse dermatitis, edema, and hyperpigmentation was seen with IMRT compared with wedges. A trend was found toward reduced acute Grade 3 or greater dermatitis (6% vs. 1%, p = 0.09) in favor of IMRT. Chronic Grade 2 or worse breast edema was significantly reduced with IMRT compared with conventional wedges. No difference was found in cosmesis scores between the two groups. In patients with larger breasts (> or =1,600 cm(3), n = 64), IMRT resulted in reduced acute (Grade 2 or greater) breast edema (0% vs. 36%, p <0.001) and hyperpigmentation (3% vs. 41%, p = 0.001) and chronic (Grade 2 or greater) long-term edema (3% vs. 30%, p = 0.007). CONCLUSION: The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based RT.     

Node-positive left-sided breast cancer patients after breast-conserving surgery: potential outcomes of radiotherapy modalities and techniques.

PURPOSE: To determine how much proton and intensity modulated photon radiotherapy (IMRT) can improve treatment results of node-positive left-sided breast cancer compared to conventional radiation qualities (X-rays and electrons) after breast-conserving surgery in terms of lower complication risks for cardiac mortality and radiation pneumonitis. METHODS AND MATERIAL: For each of 11 patient studies, one proton plan, one IMRT, and two conventional (tangential and patched) plans were calculated using a three-dimensional treatment-planning system, Helax-TMS(). The evaluation of the different treatment plans was made by applying the normal tissue complication probability model (NTCP) proposed by K?llman (also denoted the relative seriality model) on the dose distributions in terms of dose-volume histograms. The organs at risk are the spinal cord, the left lung, the heart, and the non-critical normal tissues (including the right breast). RESULTS: The comparison demonstrated that the proton treatment plans provide significantly lower NTCP values for the heart and lung when compared to conventional radiation qualities including IMRT for all 11 patients. At a prescribed dose of 50 Gy in the PTV, the calculated mean NTCP value for the patients decreased, on the average, from 14.7 to 0.6% for the lung (radiation pneumonitis) for the proton plans compared with the best plan using conventional radiation qualities. The corresponding figures for the heart (cardiac mortality) were from 2.1 to 0.5%. The figures for cardiac mortality for IMRT, tangential technique and the patched technique were 2.2, 6.7, and 2.1%, respectively. CONCLUSIONS: Protons appear to have major advantages in terms of lower complication risks when compared with treatments using conventional radiation qualities for treating node-positive left-sided breast cancer after breast-conserving surgery.     

Retreatment of the spinal cord with palliative radiotherapy

We conducted this retrospective review of patients whose spinal cord was irradiated twice to evaluate the outcome in terms of palliation and long-term side effects.

Eight patients (4 females, 4 males; median age: 67 years) were identified whose spinal cord had been irradiated twice between July 1990 and July 1997, usually for the management of bone metastases. All patients were followed up until their death from progressive disease. The Karnofsky performance score at the time of retreatment ranged from 20% to 90%. Total dose for the first treatment ranged from 29 to 50 Gy (median: 38 Gy) with single doses 1.25–3 Gy; the total dose for the retreatment ranged from 29 to 38 Gy (median: 30 Gy) with a single dose 1.8–4 Gy. The cumulative dose ranged from 59 to 88 Gy (median: 67.5 Gy). The overlap in the site of retreatment consisted of 1–3 segments, whereas in one patient, 2 single segments were treated twice. The outcome in terms of progressive disease, the palliative effects, and the development of myelopathy was assessed retrospectively.

The median interval to reirradiation was 30 months (range: 6–63 months), and the median follow-up after the last treatment was 16 months (range: 5–44 months). After reirradiation, 4/7 patients experienced complete pain relief, 2/7 patients experienced minor pain relief, and only 1 patient showed no change. Two patients with paraparesis experienced complete recovery. All patients tolerated retreatment very well. No serious acute side effects requiring any therapy were seen. During follow-up, no patient showed treatment-induced neurologic abnormalities affecting motor and sensory function, and all patients were able to walk and were continent for stool and urine.

On the basis of the findings in this limited number of patients, it is not possible to give clear and general recommendations concerning the optimal total dose and fraction size that will have maximal palliative effects and minimal side effects. However, for the purpose of palliation, retreatment within the dose range used at our institution should be considered, taking the patient’s expected life span and clinical symptoms into account.     

Gamma Knife radiosurgery for numerous brain metastases: is this a safe treatment?

Gamma Knife (GK) radiosurgery has recently been employed in patients with numerous brain metastases (METs), even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain (WB), with such treatment, have not been determined.

Since the GammaPlan ver. 5.10 (ver. 5.31 is presently available, Leksell GammaPlan) became available in November 1998, 92 GK procedures have been performed for 80 patients with 10 or more brain METs at our facility. The median lesion number was 17 (range: 10–43) and the median cumulative volume of all tumors was 8.02 cc (range: 0.46–81.41 cc). The median selected dose at the lesion periphery was 20 Gy (range: 12–25 Gy). Based on these treatment protocols, the cumulative irradiation dose was computed.

The median cumulative irradiation dose to the WB was 4.71 (range: 2.16–8.51) Gy. The median brain volumes receiving >2 Gy, >5 Gy, >10 Gy, >15 Gy, and >20 Gy were 1105 (range 410–1501) cc, 309 (46–1247) cc, 64 (13–282) cc, 24 (2–77) cc, and 8 (0–40) cc, respectively.

The cumulative WB irradiation doses for patients with numerous radiosurgical targets were not considered to exceed the threshold level of normal brain necrosis.     

Postoperative radiotherapy for head and neck squamous cell carcinomas: Feasibility of a biphasic accelerated treatment schedule

: It has been suggested that postoperative tumor cell proliferation may influence the outcome of advanced head and neck squamous cell carcinomas treated by surgery and postoperative radiotherapy. This Phase I pilot study was undertaken to determine the feasibility of a biphasic accelerated radiotherapy regimen with early and late concomitant boost delivery for postoperative treatment of patients with advanced head and neck cancers.

: From April 1993 to April 1994, 29 patients with advanced head and neck cancers were enrolled in this study after they underwent complete surgical resection. The basic radiation course delivered a median dose of 49 Gy in 25 fractions over 5 weeks at 1.8–2 Gy/fraction. The concomitant boost was delivered to the high-risk areas as a second daily fraction during the first (1.4 Gy/fraction) and fifth weeks (1.6 Gy/fraction). The total dose to the high-risk areas was 64 Gy in 35 fractions over 5 weeks.

: Twenty-seven patients (93%) completed the treatment without interruptions. Only two patients experienced severe acute toxicity requiring treatment breaks of 6 and 8 days, respectively. All patients developed confluent mucositis; in 69% of the cases it covered >50% of the treated surface. No patient developed Grade 5 (ulceration/bleeding) mucosal reaction. Mucositis required a median time of 7 weeks for complete healing (range 3–43. Two patients developed transient bone exposure. The median weight loss was 5.5% of pretreatment body weight (range 1.2–17.1%), and four patients required nutritional with nasogastric feeding tube.

: The results of this study show that this biphasic acceleration regimen is feasible with acceptable acute toxicity.     

乳腺癌调强放射治疗和常规切线野治疗的三维剂量学研究

背景与目的:乳房保留治疗已在早期乳腺癌患者中逐渐推广应用,其中全乳根治性放疗的标准技术通常采用常规切线野技术。调强放射治疗(intensity-modulatedradiotherapy,IMRT)技术有望在保障相同疗效的同时进一步减少放疗并发症,提高生活质量。本研究利用三维计划系统评价全乳IMRT的剂量学优势与适应证。方法:选择10例接受保乳手术的Tis～2N0M0早期乳腺癌病例,利用三维治疗计划系统为每例患者设计两种全乳放射治疗计划,切线野常规计划与IMRT计划,处方剂量均为5000cGy。用剂量体积直方图(dosevolumehistograms,DVH)来比较各种计划中计划靶体积(planningtargetvolume,PTV)、危及器官(organsatrisks,OARs)的剂量学差异。结果:靶区覆盖率在两种计划中相似,分别为98.3%和97.7%。与常规计划比较,IMRT计划的PTV接受<95%处方剂量与>103%处方剂量的体积百分比之和(inhomogeneityindex,IHI)从29.9%减少到2.9%,PTV接受至少105%处方剂量照射的体积百分比(V105%)从28.2%减少到0.6%;IMRT计划改善IHI和减少V105%的平均值在PTV较大的患者中优势更明显。左侧患者中冠状动脉的最大剂量(Dmax)以及心脏的平均剂量(Dmean)分别从5057.1cGy减少到4832.9cGy和从629.8cGy到450.7cGy;右侧患者肝脏的Dmean从283.9cGy减少到172.0cGy;所有患者中同侧肺的Dmean、至少接受20Gy照射的体积百分比(V20)分别从925.2cGy减少到765.9cGy,从16.0%到15.3%,Dmean与V20的平均值在IMRT计划中减少的百分比在不同射野中心肺厚度(centrallungdistance,CLD)亚组中分别是14.7%与20.9%,7.0%与12.9%;对侧乳腺和对侧肺的Dmean也分别从75.4cGy减少到20.3cGy和从30.9cGy到16.1cGy。结论:全乳IMRT的剂量学优势主要在于保证靶区覆盖率的前提下,显著改善靶区的剂量分布均匀性并一定程度上降低OARs的受照剂量与容积。乳房体积和CLD较大的病例可以通过IMRT技术获得更好的剂量学结果。     

Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: use of dose-volume constraints to achieve rectal isotoxicity

PURPOSE: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. METHODS AND MATERIALS: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage < or = T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. RESULTS: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No significant difference by dose level was seen in the 2-year rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%, 14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and 79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035). CONCLUSIONS: High doses (79.2 Gy) were safely delivered in selected patients by our adaptive radiotherapy process. Under the rectal dose-volume histogram constraints for the dose level selection, the risk of chronic rectal toxicity is similar among patients treated to different dose levels. Therefore, rectal chronic toxicity rates reflect the dose-volume cutoff used and are independent of the actual dose levels. On the other hand, a larger PTV will increase the rectal wall dose and chronic rectal toxicity rates. PTV volume and dose constraints should be defined, considering their potential benefit.     

Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience

PURPOSE: To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy.The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. CONCLUSION: Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.