George Shenouda

Using proton magnetic resonance spectroscopic imaging to predict in vivo the response of recurrent malignant gliomas to tamoxifen chemotherapy.

OBJECTIVEnMost patients with a malignant glioma spend considerable time on a treatment protocol before their response (or nonresponse) to the therapy can be determined. Because survival time in the absence of effective therapy is short, the ability to predict the potential chemosensitivity of individual brain tumors noninvasively would represent a significant advance in chemotherapy planning.nnnMETHODSnUsing proton magnetic resonance spectroscopic imaging (1H MRSI), we studied 16 patients with a recurrent malignant glioma before and during treatment with high-dose orally administered tamoxifen. We evaluated whether 1H MRSI data could predict eventual therapeutic response to tamoxifen at the pretreatment and early treatment stages.nnnRESULTSnSeven patients responded to tamoxifen therapy (three with glioblastomas multiforme; four with anaplastic astrocytomas), and nine did not (six with glioblastomas multiforme; three with anaplastic astrocytomas). Responders and nonresponders exhibited no differences in their age, sex, tumor type, mean tumor volume, mean Karnofsky scale score, mean number of weeks postradiotherapy, or mean amount of prior radiation exposure. Resonance profiles across the five metabolites measured on 1H MRSI spectra (choline-containing compounds, creatine and phosphocreatine, N-acetyl groups, lactate, and lipids) differed significantly between these two groups before and during treatment. Furthermore, linear discriminant analyses based on patients in vivo biochemical information accurately predicted individual response to tamoxifen both before and at very early treatment stages (2 and 4 wk). Similar analyses based on patient sex, age, Karnofsky scale score, tumor type, and tumor volume could not reliably predict the response to tamoxifen treatment at the same time periods.nnnCONCLUSIONnIt is possible to accurately predict the response of a tumor to tamoxifen on the basis of noninvasively acquired in vivo biochemical information. 1H MRSI has potential as a prognostic tool in the pharmacological treatment of recurrent malignant gliomas.

High Dose Tamoxifen and Radiotherapy in Patients with Glioblastoma Multiforme: A Phase IB Study

PURPOSEnTo assess the feasibility and the toxicity of adjuvant high dose tamoxifen (TAM) and postoperative brain irradiation for patients with newly-diagnosed glioblastoma multiforme (GBM).nnnMATERIAL AND METHODSnTwelve patients with histopathologically confirmed GBM entered the study. There were nine males and three females, with median age of 48.8 years (range 30-75 years). Karnofsky performance status (KPS) was 60-70% for four patients and 80-100% for eight patients. Based on the Radiation Therapy Oncology Group recursive partition analysis, there were three class III patients, six class IV, one class V, and two class VI. Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection. Two weeks post surgery, the patients were started on high dose TAM (120 mg/m2 P.O. BID for three months). Two weeks from date of starting TAM, external beam radiotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. Patients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly.nnnRESULTSnMedian follow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associated with significant vomiting, necessitating the TAM dose to be decreased at three weeks and then stopped at two months. One other patient had bilateral deep venous thrombosis after 52 weeks on TAM, although the relationship to TAM was not firmly established. There were no radiological responses after two weeks of TAM or at the end of RT. The median time to progression was 17.7 weeks (range 5.1-43.8 weeks). Median survival time was 33.4 weeks (range 10-79.7). Actuarial survival at 48 and 74 weeks was 40% and 15%, respectively.nnnCONCLUSIONnOur study shows that adjuvant high dose TAM is feasible and relatively well-tolerated. Furthermore, the combined use of high dose TAM and RT postoperatively was not associated with any significant increase in radiation-induced neurological toxicity. However, high dose TAM does not appear to improve treatment results.

Intra‐operative Echographic Localization for Radioactive Ophthalmic Plaques in Choroidal Melanoma

The objectives were to evaluate the beneficial effect of intra‐operative echographic plaque site localization and to assess the rate of complications of postplaque insertion. This paper is a descriptive study of 48 patients with choroidal melanoma who underwent iodine‐125 (I125) or ruthenium‐106 (Ru106) plaque radiotherapy with intra‐operative echographic confirmation of plaque placement with the aid of a nonradioactive plaque (dummy) at McGill University Health Centre from 1997 to 2003. Patients mean age was 63.7 years; 52% (25/48) male, 48% (23/48) female. Twenty‐seven percent (13/48) of the tumors were confined to the right eye and 73% (35/48) to the left eye. Forty‐eight percent (23/48) of the tumors were located posterior to the equator, 14.6% (7/48) were anterior to the equator, 18.7% (9/48) in posterior pole, and 18.7% (9/48) at equator. Sixty‐nine percent (33/48) received I125 and 31% (15/48) had Ru106 treatment. Ninety percent of the dummy plaques were initially positioned suboptimally and required repositioning under echographic guidance. At mean follow‐up of 18.8 months, there was no tumor‐related death or metastasis, but one patient required enucleation. The dummy plaque technique under echographic visualization resulted in reduction of radioactive exposure time during surgery of up to 50%. Intra‐operative echographic utilization has the ability to localize precisely the tumor–plaque relationship, thereby optimizing the radiation delivered to the choroidal melanoma, while minimizing the surgeons exposure time.

Mitomycin C and mitoxantrone chemotherapy for advanced breast cancer: efficacy with minimal gastrointestinal toxicity and alopecia

SummaryIn an attempt to examine the possibility of decreased toxicity in patients with advanced breast cancer who had not previously received chemotherapy, 33 women were given combination chemotherapy consisting of mitomycin C (10 mg/m2) every 6 weeks and mitoxantrone (6 mg/m2) every 3 weeks. The patients had predominantely visceral disease and received a median of two cycles of therapy. Of the 32 evaluable subjects, 15 (47%) achieved a partial response lasting a median of 7 months. Hematological toxicity was generally mild, although there were two episodes of sepsis. One patient developed hemolytic-uremic syndrome, and one subject developed pulmonary fibrosis, both presumably attributable to treatment with mitomycin C. Another patient died of hepatic failure (hepar lobatum). Thus, there were five patients who sustained life-threatening toxicities; this may have been due to the poor performance status and advanced age of some of the patients. Gastrointestinal toxicity and alopecia were minimal. Patient acceptance was high and there was an improvement in symptomatology in the majority of patients. In conclusion, mitomycin C and mitoxantrone chemotherapy is an active drug combination for the treatment of advanced breast cancer that seldom causes significant distressing gastrointestinal side effects or alopecia; however, the duration of response to this regimen appears to be shorter than that obtained with either cyclophosphamide- methotrexate - 5-fluorouracil (CMF) or cyclophosphamide - Adriamycin - 5-fluorouracil (CAF) combination chemotherapy.

Is there a detrimental effect of waiting for radiotherapy for patients with localized prostate cancer

Objective:To evaluate a possible deleterious effect of waiting time to radiotherapy on the biochemical relapse (BR) of patients with localized prostate cancer. Patients and Methods:Patients included in this retrospective study had localized prostate adenocarcinoma treated with external-beam irradiation alone. Waiting time was defined as the interval between the first consultation and the first radiation treatment. BR was defined as 3 consecutive rises of prostatic specific antigen (PSA). Patients were split into 3 groups of waiting time: group A were treated within 40 days; group B waited 41 to 80 days; group C waited >80 days to receive radiotherapy. The effect of waiting on BR was estimated by the Kaplan-Meier method. Multivariate Cox proportional hazards modeling was adjusted for known prognostic factors. Results:There were 289 patients who participated in the analysis. Median follow-up time was 6.1 year. Overall BR rate was 44% at 5 years. The median waiting time increased over the study period from 26 days in 1992 to 123 days in 2000. In adjusted multivariate analysis there was a nonsignificant higher risk of BR with waiting for 41 to 80 days (hazard ratio [HR] = 0.8; 95% confidence interval [CI] = 0.3–1.6) and for >80 days (HR = 0.6; 95% CI = 0.2–1.5) when compared with patients treated within 40 days after consultation. Conclusion:Delaying the start of radiotherapy showed little effect on the rate of BR in the group of 288 prostate cancer patients analyzed in this study.

A technique using parallel-opposed high energy electron beams for reirradiation of tumors near the spinal cord.

PURPOSEnPrevious radiation treatment of patients with recurrent Hodgkins lymphoma hampers attempts to give these patients further radiation treatment for their recurrence, because of the potential for serious radiation damage to critical normal structures within the treatment volume. The purpose of this paper is to present a technique we developed for treatment of recurrent Hodgkins lymphoma in mediastinum and hilum. The technique is based on parallel-opposed electron beams with a spinal cord shield in the posterior electron beam.nnnMETHODS AND MATERIALSnThe patient was treated with parallel-opposed 20 MeV electron beams and the spinal cord shield was shaped in such a way that the total dose from both the anterior and posterior electron beams did not exceed 33% of the prescribed tumor dose. Wax bolus was used to obtain the desired separation for the electron beams.nnnRESULTSnIn an electron beam, the dose under the spinal cord shield depends not only on the depth of the spinal cord but also on the width of the shield. For a given shield width, as the cord depth increases the relative dose under the shield first increases, reaches a maximum, and then decreases to approach the open field depth dose data at large depths. The depth at which the relative dose maximum occurs increases slowly with the shielded width. At a given depth, the relative dose decreases with an increasing shield width.nnnCONCLUSIONnParallel-opposed electron beams with a spinal cord shield in the posterior electron beam provide a viable option in treatment of tumors enveloping the spinal cord. A high tumor dose may be prescribed with a concurrent low dose to the spinal cord obtained with an appropriately shaped spinal cord shield.

Iodine-125 Radiotherapy for Choroidal Melanoma

The objective was to evaluate the effect of the gender, size, and tumor location at the time of the diagnosis on the regression response of choroidal melanoma following plaque radiotherapy treatment. The paper is a longitudinal prospective study of 28 patients diagnosed with choroidal melanoma at McGill University Health Centre from 1997 to 2002. All patients were treated with episcleral iodine‐125 (I125) plaque radiotherapy. Plaques were inserted at the tumor site under echographic visualization. All patients had medium‐size tumors, except for three. Patients had periodic ophthalmic evaluation at 3 and 6 months post radiation treatment, followed by 6‐month intervals thereafter. Patients mean age was 62 ± 15 years, 16 males and 12 females. Fifty percent of the tumors were located posterior to the equator with significant reduction in size at 12 months post plaque radiotherapy treatment. Significant regression was observed in all the tumor diameters at 5 years post treatment follow‐up. Reduction in the depth diameter was significant (P < 0.01) in both male and female groups post treatment. There was a 25% (P < 0.001) reduction in the medium size of tumors at 5‐year follow‐up. Tumors located posterior to the equator responded best to I125 plaque radiotherapy. Male patients responded better than females to treatment. Medium‐size melanoma responded well to plaque radiotherapy.

Long source-skin distance rectal irradiation technique: a review of results

PURPOSEnThis study reports the clinical outcome of fifteen patients with low rectal adenocarcinoma treated with the long source-skin distance (SSD) of endorectal irradiation technique. This method was designed at McGill University in 1986 as an alternative to the standard short SSD rectal irradiation that was developed by Papillon (Proc. R. Soc. Med. 66: 1179-1181, 1973).nnnMETHODS AND MATERIALSnBetween April 1986 and May 1993, six females and nine males were treated with this technique. Fourteen patients were treated with curative intent and one woman for palliation. The median total dose was 85 Gy (range 60-135 Gy) in a median of 3 fractions (range 3-5) over a median treatment time of 5 weeks (range 2-9.5 weeks).nnnRESULTSnWith a mean follow-up of 39 months and a median of 24 months (range 3 months-8.7 years), actuarial overall survival and disease-free survival rates are 50.8% and 71.4%, respectively, at 8.7 years. No patients have died of recurrent disease, but one patient has distant metastatic disease. One patient treated with curative intent required an abdominoperineal resection for progressive disease. Treatments were tolerated well by all patients. Four patients required steroid enemas for localized proctitis for a short period of time. They all responded well and had complete resolution of symptoms.nnnCONCLUSIONSnOur results are comparable with those in other reports in the literature. The complications are similar in type and frequency to other published series. The long SSD technique may be an acceptable alternative to the standard short SSD technique.

Intraoperative Sonographically Assisted Radioactive Iodine 125 Plaque Brachytherapy for Choroidal Melanoma Visual Acuity Outcome

The purpose of this study was to present a retrospective series of cases from a single Canadian academic center assessing visual acuity outcomes after intraoperative sonographically assisted iodine 125 (125I) plaque brachytherapy treatment.

Prognostic factors for progression in atypical meningioma

In patients with postoperative residual atypical meningiomas, by using volumetric instead of linear measurements in follow-up imaging studies, the authors detected disease progression earlier. By using this approach, treatment for recurrent disease can be instituted promptly with potentially better tumor control and less toxicity due to smaller volume of residual disease.