Kahn, Debra MD; Leung, Margaret MD, MPH; Kalivas, Kerri MD; Quanbeck, Cameron MD; Su, Andy MD Author Information

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.

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 χ2 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.

To compare late genitourinary (GU) and gastrointestinal (GI) toxicity of radiotherapy (RT) to localized fields for prostate cancer delivered using intensity-modulated RT (IMRT) versus conventional RT (ConvRT). The records of 461 patients were reviewed; 355 patients received IMRT and 106 received ConvRT. Late GU and GI toxicity were compared. Late GU toxicity rates were not significantly different (P=0.166); however, late GI toxicity rates were lower with IMRT ( P=0.001). Regression analyses demonstrated that only IMRT use (P=0.006) predicted reduction in late GI toxicity but no factors correlated with late GU toxicity. IMRT did not influence late GU toxicity but was associated with a reduction of late GI toxicity over ConvRT.

Objectives. To provide a single-institution analysis of the influence of pelvic intensity-modulated radiotherapy (RT) on acute genitourinary (CU) 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 CU 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.

Purpose/Objective: Intensity modulated radiotherapy (IMRT) is increasingly used for prostate cancer, but as yet there are no toxicity outcomes comparisons of IMRT vs conventional RT when treating the whole pelvis in both groups. In this report, we provide a single-institution analysis of the influence of whole pelvis IMRT on acute genitourinary (GU) and gastrointestinal (GI) toxicity. Materials/Methods: The records of 610 consecutive non-metastatic prostate cancer patients receiving RT were reviewed. A cohort of 49 of these patients received whole pelvis RT (WPRT), 15 with IMRT (IM-WPRT) and 34 with 4-field (4F-WPRT). All patients were initially treated to the whole pelvis followed by a boost to the prostate. The WP-IMRT treatment consisted of 7 or 9 fields (inversely planned with CORVUS using dynamic multileaf collimation) followed by an IMRT boost to the prostate. Of the 34 patients in the 4F-WPRT group, 10 received a 4F boost, 12 received a 6F conformal boost, and 12 received an IMRT boost. For the 4F-WPRT patients, median pretreatment PSA was 18.4 ng/mL, median WPRT dose was 49.3 Gy, median dose to the prostate was 70.7 Gy, and hormonal therapy was used in 21 of 34 patients. For the IM-WPRT patients, median PSA was 20.4 ng/mL, median WPRT dose was 49.6 Gy, median dose to prostate was 75.2 Gy, and hormonal therapy was used in all 15 patients. Dosimetric endpoints (derived from DVHs) for the bladder, rectum, and target for the WPRT plans were compared using the t-test; similar dosimetric analyses were done for the composite plans. Acute GU and GI toxicity were scored according to RTOG guidelines and compared using the chi-square test. Ordered logit regression analyses were performed for GU and GI toxicity using all major treatment factors (pelvic dose, final dose, hormonal therapy, pelvic technique IMRT vs non-IMRT, and boost technique IMRT vs non-IMRT) as covariates. Results: IM-WPRT treatment was superior to 4F-WPRT in reducing dose to the rectum and bladder while maintaining acceptable target coverage. In particular, the bladder and rectum DVH′s were improved using IM-WPRT for the WPRT portion of treatment (p=0.06 and p=0.03, respectively) and composite treatment (p=0.04 and p=0.01, respectively), at the expense of slightly higher target inhomogeneity in the whole pelvis treatment (p<0.01) and in the composite treatment (p=0.08). Toxicity rates are shown the table; as displayed, GU toxicity was significantly lower in the IM-WPRT group, whereas GI toxicity was similar in both groups. The ordered logit regressions showed that IMRT use for the whole pelvis portion of treatment was the only factor significantly predicting GU toxicity (p=0.05); no major treatment factor reached significance in predicting GI toxicity. Conclusions: Despite a higher final target dose in the IM-WPRT group, IM-WPRT was well-tolerated (with no grade 3 or higher GU or GI toxicity observed). Furthermore, acute GU toxicity was significantly reduced with IM-WPRT compared with 4F-WPRT; this GU toxicity reduction is likely due to reduction of bladder dose. Acute GI toxicity was, however, similar in both groups despite significantly lower rectal doses in the IM-WPRT group, perhaps due to similarities in large/small bowel dose in both groups which are not reflected in the rectal DVH computations. This work can serve as groundwork for the evaluation of IM-WPRT in a prospective setting and for the integration of IM-WPRT in consortium studies for prostate cancer treatment. Tabled 1

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.

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.

BACKGROUND The American Diabetes Association (ADA) clinical practice recommendations have been widely promoted, but they lack a geriatric-specific approach to care. We aimed to determine the style of care that endocrinologists, general internists, and geriatricians provided to their elderly patients with diabetes and to what extent these medical professionals adhered to the ADA standards. METHODS We performed a retrospective cohort study of a stratified sample of 531 diabetic patients aged 65 years and older from the endocrinology, general internal medicine, and geriatrics clinics of an urban academic medical center. RESULTS Patients of geriatricians were older, had higher comorbidity, and were more likely to be demented. The average number of diabetic complications was similar across the specialties, although patients of endocrinologists had higher prevalence of neuropathy and retinopathy compared with patients of geriatricians. Endocrinologists were more likely to use insulin, multiple types of insulin, and combined oral hypoglycemic and insulin therapies. Most patients had hemoglobin A1c measured, and average values were similarly high across specialties at 8.6%. Blood pressures were above 130/85 mm Hg in 85% of the patients. All specialties rarely measured urine microalbumin; geriatricians seldom performed fractionated cholesterol tests, and ophthalmology visits occurred in only half of the patients. CONCLUSION Endocrinologists had the most aggressive, complex diabetes treatment regimens, although geriatricians had older patients with more dementia and lower prevalence of microvascular complications. Average hemoglobin A1c levels and blood pressures were higher than recommended among patients of all three specialties. Screening for diabetic complications and hyperlipidemia was lower than advised.