L.L. Kestin

Intensity modulation to improve dose uniformity with tangential breast radiotherapy

PURPOSEnWe 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.nnnMETHODS AND MATERIALSnTen 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 beams-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.nnnRESULTSnFor 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 > or = 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.nnnCONCLUSIONnThe 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.

Prognostic Significance of Neuroendocrine Differentiation in Patients With Gleason Score 8–10 Prostate Cancer Treated With Primary Radiotherapy

PURPOSEnTo determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT).nnnMETHODS AND MATERIALSnChromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints.nnnRESULTSnMedian follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (<1% n = 21, 1-10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED.nnnCONCLUSIONSnFor Gleason score 8-10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.

Differences in disease presentation, treatment outcomes, and toxicities in African American patients treated with radiation therapy for prostate cancer.

ObjectivesWe analyzed differences in disease presentation, outcomes, and toxicities between African American (AA) and White (W) men treated with definitive radiation therapy for their prostate cancer. MethodsThree thousand one hundred eighty cases of prostate cancer treated with various radiation modalities at a single institution were reviewed. The cohort consisted of 92% W patients and 8% AA patients. Clinical and pathologic characteristics at presentation, treatment outcomes, and related toxicities were analyzed between the 2 groups. The median follow-up was 6.6 years (0.6 to 22.4 y). ResultsAt presentation, AA men were younger (P<0.001) and more likely to have a Gleason score of ≥7 (47.9% vs. 39.2%, P=0.006). No difference in the 5 or 10-year rates of biochemical failure, disease-free survival, or distant metastases were noted. Although there was a trend for improved 10-year overall survival for AA men (65.3% vs. 57.4%, P=0.06), cause-specific survival was significantly improved at 10 years (98.6% vs. 90.6%, P=0.002). Similar findings were seen when controlling for radiation therapy dose, the use of hormonal therapy, and modality of radiation therapy used. Overall, genitourinary/gastrointestinal toxicities were similar regardless of the modality used. ConclusionsDespite differences in presenting characteristics, AA men did not have inferior clinical outcomes but rather improved cause-specific survival when treated with standard of care radiation therapy. Regardless of the treatment modality used, toxicities between AA and W men were comparable.