An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer.

Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.

Postprostatectomy target-normal structure overlap volume differences using computed tomography and radioimmunoscintigraphy images for radiotherapy treatment planning.

PURPOSE: The purpose of this study was to analyze regions of uptake in normal structures on postprostatectomy radioimmunoscintigraphy (RIS) images by evaluating differences in the overlap volumes of prostate fossa clinical target volume (CTV) and planning target volume (PTV) using correlative computed tomography (CT) images. MATERIALS AND METHODS: The electronic records of 13 patients who received external beam radiotherapy postprostatectomy and who underwent a vessel-based RIS/CT registration were reviewed. For each patient, the RIS-defined CTV (CTV(RIS)) was compared (in terms of the overlap volume with the surrounding bladder, rectum, pubic symphysis, and penile bulb) with the CT-defined CTV(pre) before this registration and also with CTV(post) (the final target volume used for treatment). Similar analyses were done for PTV(RIS), PTV(pre), and PTV(post) defined in each case to be the corresponding CTV + 1-cm margin. RESULTS: CTV(RIS) overlapped significantly more with the bladder, rectum, and symphysis, but not with the penile bulb, than did either the CTV(pre) or CTV(post). However, the corresponding PTV analyses revealed no significant differences between any of the overlap volumes of any of the PTVs with the bladder, rectum, and penile bulb, but did reveal a significant difference between the PTV(RIS) and PTV(post) overlap volumes with the symphysis compared with PTV(pre) overlap volumes with the symphysis. CONCLUSIONS: On RIS images, there appear to be areas of uptake in the bladder, rectum, and pubic symphysis but not the penile bulb; however, the dosimetric consequences of this uptake for radiation treatment planning are minimal on the bladder, rectum, and penile bulb, but require segmentation for dose reduction to the pubic symphysis.

A case study of radiotherapy planning for a bilateral metal hip prosthesis prostate cancer patient.

The purpose of this report is to communicate the observed advantage of intensity-modulated radiotherapy (IMRT) in a patient with bilateral metallic hip prostheses. In this patient with early-stage low-risk disease, a dose of 74 Gy was planned in two phases--an initial 50 Gy to the prostate and seminal vesicles and an additional 24 Gy to the prostate alone. Each coplanar beam avoided the prosthesis in the beam's eye view. Using the same target expansions for each phase, IMRT and 3D-conformal radiotherapy (CRT) plans were compared for target coverage and inhomogeneity as well as dose to the bladder and rectum. The results of the analysis demonstrated that IMRT provided superior target coverage with reduced dose to normal tissues for both individual phases of the treatment plan as well as for the composite treatment plan. The dose to the rectum was significantly reduced with the IMRT technique, with a composite V 80 of 35% for the IMRT plan versus 70% for 3D-CRT plan. Similarly, the dose to the bladder was significantly reduced with a V 80 of 9% versus 20%. Overall, various dosimetric parameters revealed the corresponding 3D-CRT plan would not have been acceptable. The results indicate significant success with IMRT in a clinical scenario where there were no curative alternatives for local treatment other than external beam radiotherapy. Therefore, definitive external beam radiation of prostate cancer patients with bilateral prosthesis is made feasible with IMRT. The work described herein may also have applicability to other groups of patients, such as those with gynecological or other pelvic malignancies.

Chronic genitourinary and gastrointestinal toxicity of prostate cancer patients undergoing pelvic radiotherapy with intensity-modulated versus 4-field technique.

PURPOSE: To compare chronic GU and GI toxicity of pelvic radiotherapy delivered using intensity-modulated radiotherapy (IMRT) versus conventional 4-field technique. METHODS: The records of consecutive prostate cancer patients receiving RT at a single institution with a minimum follow-up of 120 days were reviewed; 48 of these patients received a prostate boost preceded by pelvic radiotherapy (PRT), 14 with IMRT (IM-PRT), and 34 with 4-field (4F-PRT). Dosimetric endpoints for the bladder, rectum, composite, and target for the PRT plans were compared using the 2-tailed t test. Late RTOG GU and GI toxicity were compared using the chi test. Ordered logit regression analyses were performed using all major patient, disease, and treatment factors as covariates. RESULTS: IM-PRT demonstrated superior bladder and rectum dosimetric endpoints over 4F-PRT for the PRT portion of the treatment and for the composite treatment at the expense of higher target inhomogeneity in the PRT portion of the treatment plan. Late GU toxicity was significantly lower in the IM-PRT group (P < 0.001), whereas late GI toxicity was similar in both groups (P = 0.44). When considering a similar follow-up interval in both groups, however, the difference in GU toxicity only reached a trend (P = 0.10). The regression analyses showed that no factor, including IMRT, reached significance in predicting GU or GI toxicity. CONCLUSION: Use of pelvic IMRT for prostate cancer patients was not associated with reduction of late GI toxicity but was associated with a small reduction of late GU toxicity. This reduction of late GU toxicity warrants further exploration in consortium studies.

Intensity-modulated versus conventional pelvic radiotherapy for prostate cancer: analysis of acute toxicity.

OBJECTIVES: To provide a single-institution analysis of the influence of pelvic intensity-modulated radiotherapy (RT) on acute genitourinary (GU) and gastrointestinal (GI) toxicity. METHODS: The records of 610 consecutive patients with prostate cancer receiving RT were reviewed. Of these 610 patients, 49 had received a prostate boost preceded by pelvic RT (PRT), 15 intensity-modulated PRT (IM-PRT), and 34 four-field PRT (4F-PRT). The dosimetric endpoints for the bladder, rectum, and target for the PRT plans were compared using the paired t test; similar dosimetric analyses were done for the composite plans. Acute GU and GI toxicity were compared using the chi-square test. Ordered logit regression analyses were performed using all major treatment factors as covariates. RESULTS: The bladder and rectum dosimetric endpoints were improved for IM-PRT compared with 4F-PRT for the PRT portion of the treatment plan (P = 0.06 and P = 0.03, respectively) and for the composite treatment plan (P = 0.04 and P = 0.01, respectively), at the expense of greater target inhomogeneity in the PRT portion of the treatment plan (P < 0.01). GU toxicity was significantly lower in the IM-PRT group (P < 0.001), and GI toxicity was similar in both groups (P = 0.637). The regression analyses showed that intensity-modulated RT for the pelvic portion of treatment was the only factor significantly predicting for GU toxicity (P = 0.05); no major treatment factor reached significance in predicting GI toxicity. CONCLUSIONS: Compared with 4F-PRT, the use of IM-PRT improved dosimetric outcomes, was not associated with a reduction in acute GI toxicity, and was associated with a reduction in acute GU toxicity in the treatment of prostate cancer.