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IntroductionThis study aimed to explore the potential for computed tomography (CT) perfusion and 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting sites of future progressive tumour on a voxel-by-voxel basis after radiotherapy and chemotherapy. MethodsTen patients underwent pre-radiotherapy magnetic resonance (MR), FDG-PET and CT perfusion near the end of radiotherapy and repeated post-radiotherapy follow-up MR scans. The relationships between these images and tumour progression were assessed using logistic regression. Cross-validation with receiver operating characteristic (ROC) analysis was used to assess the value of these images in predicting sites of tumour progression. ResultsPre-radiotherapy MR-defined gross tumour; near-end-of-radiotherapy CT-defined enhancing lesion; CT perfusion blood flow (BF), blood volume (BV) and permeability-surface area (PS) product; FDG-PET standard uptake value (SUV); and SUV:BF showed significant associations with tumour progression on follow-up MR imaging (P < 0.0001). The mean sensitivity (±standard deviation), specificity and area under the ROC curve (AUC) of PS were 0.64 ± 0.15, 0.74 ± 0.07 and 0.72 ± 0.12 respectively. This mean AUC was higher than that of the pre-radiotherapy MR-defined gross tumour and near-end-of-radiotherapy CT-defined enhancing lesion (both AUCs = 0.6 ± 0.1, P ≤ 0.03). The multivariate model using BF, BV, PS and SUV had a mean AUC of 0.8 ± 0.1, but this was not significantly higher than the PS only model. ConclusionPS is the single best predictor of tumour progression when compared to other parameters, but voxel-based prediction based on logistic regression had modest sensitivity and specificity.

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PURPOSE: To report our experience using high-dose-rate (HDR) brachytherapy with computed tomographic (CT) imaging for locally advanced cervix cancer, using available resources to optimize the treatment. METHODS AND MATERIALS: Fifty-seven women with cervix cancer were treated between September 2004 and March 2008. Patients received external radiotherapy, HDR brachytherapy (7 Gy x4) and concurrent chemotherapy. CT planning was done for each insertion. RESULTS: Median age was 53 years (range, 29-89 years); majority (49%) had International Federation of Gynecology and Obstetrics stage IIB. The median follow-up was 22.6 months. There were 4 patients who required laser coagulation for rectal bleeding, and one patient required hemicolectomy for sigmoid stricture. There was no grade 3 or 4 genitourinary toxicity. The Kaplan-Meier overall survival, relapse free, central pelvic and pelvic control at 3 years was 86%, 62%, 89%, and 83%, respectively. Pelvic control for tumors 2 to 5 cm was 95% and 84% for tumors greater than 5 cm. CONCLUSIONS: Our early experience confirms that CT-based HDR brachytherapy for cervix cancer achieves disease control comparable to other published series. At the same time, conformal avoidance of organs at risk allows for low rates of toxicity.

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PURPOSE: To describe our clinical experience using a unique single-isocenter technique for frameless intensity-modulated stereotactic radiosurgery (IM-SRS) to treat multiple brain metastases. METHODS AND MATERIALS: Twenty-six patients with a median of 5 metastases (range, 2-13) underwent optically guided frameless IM-SRS using a single, centrally located isocenter. Median prescription dose was 18 Gy (range, 14-25). Follow-up magnetic resonance imaging (MRI) and clinical examination occurred every 2-4 months. RESULTS: Median follow-up for all patients was 3.3 months (range, 0.2-21.3), with 20 of 26 patients (77%) followed up until their death. For the remaining 6 patients alive at the time of analysis, median follow-up was 14.6 months (range, 9.3-18.0). Total treatment time ranged from 9.0 to 38.9 minutes (median, 21.0). Actuarial 6- and 12-month overall survivals were 50% (95% confidence interval [C.I.], 31-70%) and 38% (95% C.I., 19-56%), respectively. Actuarial 6- and 12-month local control (LC) rates were 97% (95% C.I., 93-100%) and 83% (95% C.I., 71-96%), respectively. Tumors 1.5 cm (98% vs. 90%, p = 0.008). New intracranial metastatic disease occurring outside of the treatment volume was observed in 7 patients. Grade >or=3 toxicity occurred in 2 patients (8%). CONCLUSION: Frameless IM-SRS using a single-isocenter approach for treating multiple intracranial metastases can produce clinical outcomes that compare favorably with those of conventional SRS in a much shorter treatment time (<40 minutes). Given its faster treatment time, this technique is appealing to both patients and personnel in busy clinics.

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The purpose of this study was to evaluate the dosimetry of single fraction, single-isocenter intensity-modulated radiosurgery (IMRS) plans for multiple intracranial metastases and to compare Helical Tomotherapy (HT). Ten treatment plans with 3-6 brain metastases treated with IMRS were re-planned with HT. The mean number of lesions was 5 and mean PTV 22 cm(3). The prescribed dose was 16-20 Gy. The mean V100% was similar for IMRS and HT, and the mean conformity index was 1.4, mean Paddick confirmity index was 0.7, and mean MDPD was 1.1 for both. The mean gradient index was similar for both. The mean 50% _isodose volume was 179.2 cm(3) for IMRS and 277.0 cm(3) for HT (p=0.01). The mean maximum doses to organs at risk were lower for IMRS except brainstem and right optic nerve. For brain, the integral dose was 5.1 and 6.8 Gy-kg (p<0.001) and mean dose 4.0 and 5.4 Gy (p<0.001) for IMRS and HT, respectively. The mean treatment times were 23 (IMRS) and 41 (HT) minutes. Conformity and homogeneity indices were equivalent and sparing of the organs at risk was clinically acceptable for both IMRS and HT. Though the gradient index was similar for IMRS and HT, the mean 50% isodose volume and integral dose to normal brain were lower for IMRS as was treatment time.

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PURPOSE: To determine the maximum tolerated dose of 3D conformal radiotherapy in combination with Cisplatin for patients with recurrent malignant gliomas. METHODS: From 1999-2003, nine patients with recurrent malignant glioma received fractionated radiotherapy and Cisplatin (20 mg/m2/d IV on days 1-5) in a Phase I radiation dose escalation trial. Three sequential dose levels were evaluated: 25 Gy, 30 Gy, and 35 Gy, using 5 Gy fractions. All patients received prior external beam radiation (median dose 59.4 (20-60) Gy) and five patients received prior chemotherapy. RESULTS: Six male and three female patients were enrolled with a median age of 52 years, and a median Karnofsky performance status score of 70. The median re-irradiated tumor volume was 18.9 (0.1-78.5) cm3 and the median follow-up was 8.8 (3.2-31.2) months. One patient (30 Gy/ 6 fractions) experienced medically reversible acute grade 3 toxicity. A second patient (35 Gy/ 7 fractions) experienced acute grade 2 toxicity and histology showed tumor and radiation effect. A third patient (25 Gy/ 5 fractions) experienced late grade 3 toxicity from radiation necrosis. The radiological responses consisted of complete response (1 patient), partial response (1 patient), and stable disease (2 patients). The median overall survival was 8.8 months (95% CI 8.0-9.9), and the median disease free interval was 2.0 months (95% CI 1.4-4.4). Seven patients received chemotherapy following re-irradiation and Cisplatin. CONCLUSION: The maximum tolerated dose of 3D conformal fractionated radiotherapy was 30 Gy in 6 fractions with low dose Cisplatin, which was well tolerated in terms of acute toxicity for our patient population. This regimen demonstrated only modest efficacy in the treatment of recurrent malignant glioma. Combinations of conformal re-irradiation and other systemic agents may merit investigation. Currently our recommended dose is 30 Gy in 6 fractions for selected patients.

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PURPOSE: To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin (Bowen's disease). We focused on the local control rate and the toxicity according to the biologically effective dose (BED). METHODS AND MATERIALS: A retrospective review was performed on 44 patients with Bowen's disease treated at Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients, whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp, 9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%). Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen: some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4 toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months. RESULTS: The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment lesion size was 2.65 cm(2) (range, 0.07-34.56 cm(2)). Complete remission was achieved in 42 patients, with follow-up unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1-1.5 years after complete remission. One recurrence was Bowen's disease (local); the others were squamous cell carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant cutaneous site. As of last follow-up, 32 patients (73%) were known to be alive. Median follow-up was 2.6 years (range, 0-11.8 years). All but 3 patients were disease-free at last follow-up, 1 of whom died with distant, but not local disease. The 5-year overall survival rate was 68%. Biologically effective dose was not associated with recurrence. The crude local control rate was 93%. There was a trend toward higher radiation doses for smaller pretreatment tumor and field sizes. The BED did not correlate with Grade 4 toxicity; however, the three cases of Grade 4 toxicity occurred in patients treated with hypofractionated regimens (dose per fraction >4 Gy) for extremity lesions. CONCLUSIONS: Radiation therapy is an effective treatment option for Bowen's disease of the skin. Local recurrences seem to be equally low in patients treated with high- and low-dose regimens. Avoiding hypofractionated regimens (dose per fraction >4 Gy) in extremity locations might reduce the risk of Grade 4 toxicity.

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