Showing papers by "Barbara Fisher published in 2012"

Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience

Abstract: The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60–86), median KPS was 80 (range 30–100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI, 4.5–8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked (P-value 0.045.) Median OS was 9.3 months (95% CI, 5.9–11.8) (P-value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI, 9.9–19.3) (P-value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy.

Initial treatment patterns over time for anaplastic oligodendroglial tumors.

Abstract: Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach to treatment. We sought to determine patterns of treatment delivered over time and identify clinical correlates of specific strategies using an international retrospective cohort of 1013 patients diagnosed from 1981-2007. Prior to 1990, most patients received radiotherapy (RT) alone as initial postoperative treatment. After 1990, approximately 50% of patients received both RT and chemotherapy (CT) sequentially and/or concurrently. Treatment with RT alone became significantly less common (67% in 1980-1984 vs 5% in 2005-2007, P < .0001). CT alone was more frequently administered in later years (0% in 1980-1984 vs 38% in 2005-2007; P < .0001), especially in patients with 1p19q codeleted tumors (57% of codeleted vs 4% with no deletion in 2005-2007; P < .0001). Temozolomide replaced the combination of procarbazine, lomustine, and vincristine (PCV) among patients who received CT alone or with RT (87% vs 2% in 2005-2007). In the most recent time period, patients with 1p19q codeleted tumors were significantly more likely to receive CT alone (with temozolomide), whereas RT with temozolomide was a significantly more common treatment strategy than either CT or RT alone in cases with no deletion (P < .0001). In a multivariate polytomous logistic regression model, the following were significantly associated with type of treatment delivered: date (5-year interval) of diagnosis (P < .0001), 1p19q codeletion (P < .0001), pure anaplastic oligodendroglioma histology (P < .01), and frontal lobe predominance (P < .05). Limited level 1 evidence is currently available to guide treatment decisions, and ongoing phase III trials will be critical to understanding the optimal therapy.

Use of Protoporphyrin Fluorescence to Determine Clinical Target Volume Margins for Nonmelanotic Skin Cancers Treated With Primary Radiation Therapy

Abstract: PURPOSE Non-melanotic skin cancers remain the most commonly diagnosed cancers. Radiotherapy and surgery are the most common treatment options. Radiotherapy has a recurrence rate of up to 20% for basal or squamous cell cancers. One of the difficulties is to determine the extent of disease for poorly demarcated tumors. This study utilizes protoporphyrin (PpIX) fluorescence to provide information on the extent of subclinical disease for poorly demarcated tumors treated with radiotherapy. MATERIALS AND METHODS For 33 patients, PpIX photo-delineation was used to determine the clinical target volume (CTV2), which was compared to current conventional margins used to account for microscopic disease. RESULTS The use of PpIX photo-delineation demonstrated a significantly larger CTV of 15 mm compared to the conventional 10 mm (p = 0.03) for poorly demarcated lesions. A larger CTV was also demonstrated with PpIX photo-delineation for all basal cell carcinomas (13 mm, p = 0.03) as well as for non-nasal lesions (14 mm, p = 0.04). A trend towards an increased CTV was also noted for squamous cell carcinomas (16 mm, p = 0.19) and nasal primary sites (14 mm, p = 0.11). Nasal primary malignancies had multifocal PpIX uptake in 94% of cases. There was one case of local recurrence and one case of distant recurrence, with an average follow-up time of 22 months. CONCLUSIONS The margins currently used to account for subclinical disease may underestimate the extent of microscopic spread for poorly demarcated tumors. Longer follow-up with larger pools of patients are necessary to determine if using PpIX photo-delineation translates into significantly improved clinical outcomes.

Multidisciplinary Assessment and Reporting of Fitness to Drive in Brain Tumor Patients: A Gray Matter

Abstract: 6130 Background: In some jurisdictions, there is a legal requirement for physicians to report medically unfit drivers. Objectives of this study are to determine physician knowledge and attitudes on...

Response to Weltman and Fleury Malheiros, re Lassman et al.

Abstract: In Reply to Weltman and Fleury Malheiros: We thank Drs. Weltman and Fleury Malheiros for their comments on our recent article.1 We agree that our analyses were performed on a retrospective dataset, and interpretations are thus subject to limitations and potential biases inherent to any retrospective study. For example, as we discussed in the article, neither central review of pathology nor imaging was performed. Multivariate analyses attempted to control for potential confounding variables, but only a randomized prospective study would definitively address this concern. However, we believe that our conclusions (and cross-comparisons) are supported not only by our own observations but also by recent data and treatment trends in neuro-oncology. For example, in our study, treatment group imbalances did not contribute to differences in outcome in the Cox model. Groups were reasonably well balanced for potential confounders, such as performance status. In addition, Weltman and Fleury Malheiros suggest that standard of care for anaplastic oligoendrogliomas includes radiotherapy as part of the initial treatment regimen. We agree that radiotherapy has well-established efficacy and, for many years, was the standard approach. However, treatment options have evolved since the initial studies during the 1960s–1980s cited by Drs. Weltman and Malheiros. It is now well established that oligodendrogliomas, especially those harboring 1p19q co-deletion, respond to chemotherapy. For example, the recently publicized long-term follow-up of RTOG 9402 demonstrated that chemo-radiotherapy doubled median survival relative to radiotherapy alone in 1p19q co-deleted cases (14.7 vs. 7.3 years).2 Moreover, the German NOA-04 trial of newly diagnosed anaplastic gliomas also suggested that primary chemotherapy is equi-efficacious as primary radiotherapy.3 Furthermore, survival with 1p19q codeleted anaplastic oligodendrogliomas is at least several years. Accordingly, radiotherapy-induced dementia as a late toxicity4 is a real concern. Consequently, many neuro-oncologists advocate for chemotherapy alone and defer radiotherapy until disease progression in 1p19q codeleted cases. The same concern is well established in the controversies surrounding late neuro-cognitive toxicity from early radiotherapy in the treatment of low-grade gliomas, primary central nervous system lymphoma, and resected brain metastases. Therefore, the acknowledged limitations of our retrospective design notwithstanding, our results are concordant with these studies suggesting that overall survival was not compromised by deferring radiotherapy.1 Absent a clear survival advantage, deferred radiotherapy in favor of chemotherapy alone is certainly a reasonable initial strategy. We are not alone. For example, 42% of neuro-oncologists surveyed in 2005 recommended deferring radiotherapy in codeleted cases.5 Similarly, 57% of patients in our retrospective dataset who receive a diagnosis of codeleted tumors since 2005 were treated with chemotherapy alone (almost exclusively temozolomide).6 Therefore, as stated in our publication, “subject to the limitations of study design, our data suggest that initial treatment with chemotherapy alone may be a reasonable option for patients with 1p19q codeleted tumors.”1 Regardless of advised therapy, in our clinical experience, many patients refuse radiotherapy because of perceived concerns about neuro-toxicity. Therefore, although ongoing or future prospective studies may show that deferred radiotherapy adversely affects survival, concerns about cognitive injury are important in determining optimal therapy, and survival may not be the only end point of clinical importance. The CATNON or CODEL phase III trials (for non- or codeleted anaplastic gliomas, respectively) may help to assess quality of life outcomes. Clearly, neuro-oncology is a multidisciplinary field, and treatment requires individualization that depends on discussion among both physicians and patients of risks and benefits of various strategies.