Gamal El-Husseiny

Malignant fibrous histiocytoma: a retrospective study of 109 cases.

The purpose of this report is to assess the prognostic factors that could influence management and clinical outcome of malignant fibrous histiocytoma (MFH) of soft tissues. Between 1975 and 1998, 109 patients diagnosed with MFH of the soft tissues, seen at King Faisal Specialist Hospital and Research Center, have been reviewed. Of the 109 patients, 75 were men and 34 were women. The median age at presentation was 48 years (range: 3–94). Seven patients (6%) had regional nodal disease and 10 other patients (9%) with distant metastases were excluded from survival analysis. The remaining 92 patients had localized disease and had surgery as the primary treatment modality with or without radiotherapy and/or chemotherapy. Extremities were the most common location (58%). Tumors less than 5 cm represented 32%, whereas 68% had tumors 5 cm or more. Low-grade tumors constituted 46%, and the remaining 54% were high grade. Thirty-seven percent of patients had positive surgical margins histologically after complete gross resection. The 5- and 10-year relapse-free survival (RFS) rates were 39% and 36%, respectively. Isolated local recurrence occurred in 20 patients (22%), isolated metastatic disease without local recurrence in 9 patients (10%), and combined local and metastatic disease occurred in 20 patients (22%). The overall 5- and 10-year overall survival (OS) rates were 50% and 43%, respectively. On multivariate analysis, tumor size and radiation dose were significant factors for RFS (p = 0.04 and 0.0005, respectively). In terms of OS, size, histologic grade, and surgical margins were significant factors on multivariate analysis (p = 0.001. 0.006, and 0.0001, respectively). Complete surgical resection at the time of primary tumor presentation is likely to afford the best chance for RFS and OS. Radiation therapy plays an important role, in combination with surgery for better local control, particularly in high-grade lesions, and in cases with positive surgical margins after wide complete gross excision. The role of adjuvant chemotherapy remains investigational.

Adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide in the treatment of postenucleation high risk retinoblastoma.

PURPOSE To study risk factors and outcome of children with high risk retinoblastoma who receive postenucleation vincristine, doxorubicin, and cyclophosphamide. PATIENTS AND METHODS Charts of all patients who received adjuvant chemotherapy for retinoblastoma were reviewed. Thirty-six patients were identified who received chemotherapy for high risk histopathologic features. Histopathology slides of these 36 patients were retrieved and reviewed, and the disease was staged according to the modified St. Jude staging system. The disease was unilateral in 23 patients (64%). There were 9 patients with stage I disease, 18 with stage II, and 9 with stage III. Twenty-four patients (67%) completed 12 of the 12 scheduled chemotherapy cycles, and 11 patients (30%) received 4 to 11 cycles because of relapse, disease progression, or family reasons. A life-threatening complication developed in one patient after the first cycle, and this patient received no further chemotherapy. RESULTS Five (3 with unilateral and 2 with bilateral disease) of the 36 patients developed distant metastasis and subsequently died. All had massive tumors; three had choroidal and up to surgical margin optic nerve invasion, and two had tumor extending posterior to lamina cribrosa. Six other patients had local relapse or progressive disease. All of these six patients had bilateral disease and failed in the intact eye during (three patients) or after (three patients) chemotherapy. Only two of the six patients were alive with no disease 50 and 102 months from diagnosis. With a median follow-up of 5.6 years, the 5-year and 10-year actuarial overall survival rates were 86% and 74%, respectively. The 5-year survival rates for patients with modified St. Jude stage I, II, and III disease were 100%, 91% (95% confidence interval, 57% to 100%), and 58% (95% confidence interval, 22% to 94%), respectively (P = 0.008). The survival rate was significantly different among patients with optic nerve involvement anterior to lamina cribrosa, posterior to lamina cribrosa, and surgical margin involvement (100%, 55%, and 41%, respectively; P = 0.003). Multivariate analysis showed that only the degree of optic nerve involvement (and therefore, modified St. Jude stage) was predictive of poor outcome. CONCLUSION Patients with retinoblastoma involving the optic nerve beyond the lamina cribrosa have low survival rate despite local therapy and adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide. Progression of disease in the intact eye of three patients receiving chemotherapy is of concern. Alternative chemotherapeutic agents should be considered for patients with such high risk features.

A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer

BackgroundMaintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research.MethodsThis multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs).ResultsA total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the induction and continuation maintenance therapies were generally well-tolerated, and similar proportion of patients in each arm experienced at least 1 grade 3/4 TEAE (pemetrexed/BSC, 17.9%; BSC, 18.5%).ConclusionsContinuation pemetrexed maintenance therapy resulted in promising PFS with an acceptable safety profile in a Middle Eastern population with advanced non-squamous NSCLC and is worthy of further investigation.Trial registrationNCT00606021

Low-grade Astrocytoma: A Retrospective Analysis of 102 Patients

One hundred and two patients (57 males, 45 females, median age 17 years) with histologically proven low-grade astrocytoma (grades I, II) treated between 1978 and 1994 were retrospectively analyzed at the King Faisal Specialist Hospital & Research Center. Microscopic investigation showed 50 patients (48%) with grade I tumors as opposed to 52 patients (52%) with grade II tumors. Fifteen patients (15%) had complete surgical excision, 55 (52%) had partial excision and 32 (31%) had biopsy only; 68 patients (66%) received external radiotherapy with a median dose of 54 Gy (range 45-68.5 Gy). With a median follow-up of 3.3 years, the 5 and 10 years, overall actuarial survival rates were 78% and 62%, respectively while the progression-free survival rates at 5 and 10 years were 69%, and 35%, respectively. Age and performance status were significant prognostic factors in terms of overall survival on univariate (p = 0.05 and 0.05, respectively) and multivariate analysis (p = 0.005 and 0.006, respectively).

Improved survival with combined chemo- radiotherapy in primary central nervous system lymphoma

BACKGROUND Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). METHODS All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded (4 had WBI<40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose>40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI. RESULT Of 52 patients analyzed for outcome, 36 had WBI (dose>40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. x22%, p=.029). Median follow up was 12.83±6.4 months. The hazard ratio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60 years), ECOG PS (0-2 vs. 3-4), extent of surgery (biopsy vs. debulking), solitary vs multifocal tumor and dose of radiation therapy (<50 Gy vs. >50 Gy) failed to identify any prognostic factor. CONCLUSION This retrospective comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome.