James Morris

Volumetric Modulated Arc Therapy for Delivery of Prostate Radiotherapy: Comparison With Intensity-Modulated Radiotherapy and Three-Dimensional Conformal Radiotherapy

PURPOSE Volumetric modulated arc therapy (VMAT) is a novel form of intensity-modulated radiotherapy (IMRT) optimization that allows the radiation dose to be delivered in a single gantry rotation of up to 360 degrees , using either a constant dose rate (cdr-VMAT) or variable dose rate (vdr-VMAT) during rotation. The goal of this study was to compare VMAT prostate RT plans with three-dimensional conformal RT (3D-CRT) and IMRT plans. PATIENTS AND METHODS The 3D-CRT, five-field IMRT, cdr-VMAT, and vdr-VMAT RT plans were created for 10 computed tomography data sets from patients undergoing RT for prostate cancer. The parameters evaluated included the doses to organs at risk, equivalent uniform doses, dose homogeneity and conformality, and monitor units required for delivery of a 2-Gy fraction. RESULTS The IMRT and both VMAT techniques resulted in lower doses to normal critical structures than 3D-CRT plans for nearly all dosimetric endpoints analyzed. The lowest doses to organs at risk and most favorable equivalent uniform doses were achieved with vdr-VMAT, which was significantly better than IMRT for the rectal and femoral head dosimetric endpoints (p < 0.05) and significantly better than cdr-VMAT for most bladder and rectal endpoints (p < 0.05). The vdr-VMAT and cdr-VMAT plans required fewer monitor units than did the IMRT plans (relative reduction of 42% and 38%, respectively; p = 0.005) but more than for the 3D-CRT plans (p = 0.005). CONCLUSION The IMRT and VMAT techniques achieved highly conformal treatment plans. The vdr-VMAT technique resulted in more favorable dose distributions than the IMRT or cdr-VMAT techniques, and reduced the monitor units required compared with IMRT.

Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas

The vast majority of patients treated for malignant gliomas with surgery, conventional radiation therapy, and systemic chemotherapy recur within 2 cm of their original disease site as documented by CT scanning. We have analyzed the clinical patterns of failure in patients treated with stereotactic interstitial irradiation (brachytherapy) for malignant gliomas in order to determine if this modality has altered the recurrence pattern in this disease. Between December 1985 and December 1989, 53 patients with malignant glioma were treated with stereotactic interstitial irradiation using temporary high activity iodine-125. Thirty-three patients were treated as part of a primary treatment protocol that included 5940 cGy external beam prior to implantation. Twenty patients were treated at time of recurrence. The median dose of radiation given at implantation was 5040 cGy for the primary lesions and 5450 cGy for the recurrent lesions. Twenty-two patients have suffered relapse as documented by clinical and radiographic studies. The predominant patterns of failure in these 22 patients were in the margins of the implant volume (8) and distant sites (10) within the CNS (distant ipsilateral or contralateral hemisphere, spinal axis) or extraneural. Thus, marginal and distant recurrences accounted for 82% of the relapses in our patients. We conclude stereotactic interstitial irradiation has changed the recurrence pattern in patients with malignant glioma with true local recurrence no longer being the predominant pattern of failure as is seen with conventional therapy.

New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.

PURPOSE A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.

Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis.

PURPOSE To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone. METHODS AND MATERIALS Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups. RESULTS Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500). CONCLUSIONS Propensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations.

Cavernous hemangioma of the thoracic spinal cord

SummaryA 25-year-old woman presented with a four-year history of progressive right-lower-extremity weakness and atrophy and a left hemisensory deficit was found. Metrizamide-enhanced spinal CT scan showed an intramedullary lesion at the level of T1-T2; this had expanded the cord in fusiform fashion but showed no evidence of a cystic component. Surgical resection was performed and the pathological diagnosis was cavernous hemangioma. Two and one-half years later, her left hemisensory deficit was worsening and a spinal MRI showed high signal intensity mass in the region of the previous surgery consistent with chronic hematoma which was re-evacuated with some improvement in the patients neurological condition.

Cervical chordoma presenting with intervertebral foramen enlargement mimicking neurofibroma: CT findings.

A cervical chordoma, confirmed at surgery, presented on plain spine films as a focal enlargement of the intervertebral foramen and mimicked the characteristic appearance of cervical neurofibroma. Computed tomography (CT) of the cervical spine was obtained immediately following metrizamide myelography; it demonstrated a soft-tissue mass in the enlarged intervertebral foramen that extended posteriorly to compress the spinal cord and anteriorly to compress the hypopharynx. The mass was sharply demarcated, inhomogeneous, and low in attenuation; CT density measured between those of cerebrospinal fluid and muscle. Although this CT appearance is not specific for cervical chordoma, it is unusual for neurofibroma. Cervical chordoma should be considered in the differential diagnosis of focal enlargement of cervical intervertebral foramina.

Septation and focal dilatation of ventricles associated with cryptococcal meningoencephalitis

A 35-year-old woman developed temporal lobe seizures. Isolated dilatation of the right temporal horn was demonstrated by computed tomography. She was asymptomatic for the next 10 months while on anticonvulsants before severe headaches, vomiting, and mental confusion prompted hospitalization. Both temporal horns were now dilated, there was marked periventricular edema, and cryptococci were cultured from the ventricular fluid. She succumbed after prolonged systemic and intrathecal antifungal therapy, having developed isolation and dilatation of both frontal horns and third and fourth ventricles. Cryptococcal or other fungal meningoencephalitis should be considered in the differential diagnosis of isolated dilatations of the ventricular chambers as noted in the present case.

Evaluation of the Risk of Relapse in Classical Hodgkin Lymphoma at Event-Free Survival Time Points and Survival Comparison With the General Population in British Columbia

PURPOSE Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). METHODS The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period-generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. RESULTS One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. CONCLUSION Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.

Computed tomography in opportunistic cerebral toxoplasmosis: report of two cases

Abstract Computed tomographic (CT) appearances of two cases of opportunistic cerebral toxoplasmosis are described. Both patients were severely immunosuppressed and had malignant neoplasms of the hematopoietic system. The CT findings were of low density areas in the brain and in one case there was faint enhancement after contrast injection. Differential diagnosis is discussed and importance of early diagnosis is emphasized.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study

Purpose To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). Material and methods Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. Results Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. Conclusions Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB.