Conventional versus hyperfractionated radiotherapy in locally advanced head and neck cancer

Radiotherapy is often the primary treatment of locally advanced squamous cell carcinoma of the head and neck, but the optimal fractionation schedule has been controversial. The aim of this study was to examine whether, after preceeding induction chemotherapy, hyperfractionated radiotherapy [HFRT] is superior to conventional fractionated radiotherapy [CFRT]. Patients with locally advanced squamous cell carcinoma of the head and neck were treated with three cycles of cisplatin [100 mg/m[2] D1] and 5-fluorouracil [1000 mg/m[2] D1-4], repeated every 3 weeks. Then patients were randomized to receive either CFRT at 1.8-2 Gy/fraction /day, 5 day/week to 65-70 Gy/33- 35 fractions/7 weeks or HFRT at 1.2 Gy /fraction, twice daily with a 6-hours interfraction interval, 5 days/week to 76.8 Gy/64 fractions/7 weeks. All patients in both treatment arms received concomitant chemotherapy in the form of weekly bolus injection of cisplatin [20mg/m[2]]. Of the 60 patients entered, only 53 patients were evaluable for outcomes. The primary end points were local control and progression- free survival. Chemotherapy was well tolerated, the overall response rate after induction chemotherapy was 73.6%, including 13.2% complete response rate. After completion of radiotherapy, patients treated with HFRT had an overall response rate of 96.2% versus 77.8% in CFRT [P= 0.04] and complete response rate of 65.4% in HFRT versus 40.7% in CFRT [P=0.01]. After a median follow- up of 28 months, overall survival was 57.7% in HFRT versus 44.4% in CFRT [P= 0.07]. The 2-year progression-free survival was 44% in HFRT versus 23.8% in CFRT [P=0.03]. The 2- year locoregional control was significantly higher in HFRT [58.8%] than those with CFRT [36.4%] [P=0.02]. The incidence of local recurrence rate was 41.2% in HFRT versus 63.6% in CFRT [P=0.02]. However, the incidence of distance metastases was 7.7% in HFRT versus 11.1% in CFRT [P=0.4]. Patients treated with HFRT had significantly greater acute side effects compared to CFRT. However, there was no significant increase of late effects. After induction chemotherapy, hyperfractionated radiotherapy is more efficaceous than conventional fractionated radiotherapy in locally advanced squamous cell head and neck cancer. Acute but not late effects are increased, but it is tolerable and manageable

Prognostic role of matrix metalloproteinase-9 [MMP-9] in patients with osteosarcoma

Osteosarcoma [OS] is a highly malignant bone tumor and is the most frequent malignant bone tumor in children and adolescents. The majority of patients with this disease harbor "micrometastasis" at diagnosis, a fact that demonstrates the need for molecular variables which can predict the presence or absence of micro-metastasis. Matrix metalloproteinases [MMPs] are a class of matrix - and basement membrane-degrading enzymes whose expression is associated with tumor cell invasive and metastatic behavior. One of these enzymes, MMP-9 is expressed in developing and remodeling bone in OS cell lines. The current study investigated the expression of MMP-9 by immunohistochemistry and its correlation with the prognosis in OS patients treated at Mansoura Clinical Oncology and Nuclear Medicine Department. MMP-9 was examined immunohistochemically using a monoclonal antibody in 20 patients with OS. The range of follow-up was 16 to 53 months with a median of 31.5 months. Correlation of the positivity of staining with prognosis was analyzed with Kaplan-Meier method. We found that MMP-9 immunohistochemical expression was positive in 85% of cases [17/20] and increased MMP-9 expression was significantly associated with poor prognosis in overall, metastasis-free and recurrence-free survivals [p=0.001, 0.001, and 0.002 respectively]. These results suggest that MMP-9 expression is common in OS and demonstrate the correlation of MMP-9 expression and the oncological outcome of OS patients

quality of care for patients with advanced ovarian carcinoma

To assess the quality of care for patients with advanced ovarian carcinoma at Mansoura University Teaching Hospital. Case notes of 96 patients with advanced ovarian carcinoma [stages III-IV] were reviewed. Operative intervention was carried out by Gynecologists in 50 patients and optimal debulking was achieved in 19 [38%]. A combined team of Gynecologists and Surgeons achieved optimal debulking in 17/21 [81%], while general surgeons achieved optimal debulking in 5/25 [20%] of patients. 78% of patients completed 6 cycles of platinum based chemotherapy. The median progression-free and overall survival was 16 and 22.9 months respectively. Optimal cytoreduction was the single favorable prognostic factor. Patients were managed on individual basis with no specialization or multi-disciplinary team management. Multidisciplinary surgical management achieved the best survival for patients with advanced ovarian carcinoma. Centralization of care and surgical sub-specialization are still suboptimal in Mansoura

Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer using an oxaliplatin-containing regimen: a phase II study

The combination of radiation, 5-fluorouracil and oxaliplatin in locally advanced rectal cancer has been shown to be feasible in phase 1 trials. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting. Between December 2003 and Jan 2006, 46 patients with locally advanced rectal adenocarcinoma entered the study. Radiotherapy was delivered with a fourfield technique to a dose of 50.4Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5 [from days 1-5 and 29-33] in the form of oxalipatin 130mg/m[2] on day 1 plus 30 minute infusion of 100mg/m[2] L-folinic acid and continuous infusion of fluorouracil 350mg/m[2] for 5 days. Surgery was planned 6 weeks later. All patient completed treatment without modification except 10/46 patients [21.7%] who experienced grade 3/4 toxicity which necessitates treatment interruption and further dose reduction. Surgery was performed in 44 patients as 2 cases developed metastasis before the time of the planned surgery. An objective response was seen in 31 patients [67.4%]. Sphincter-saving surgery was possible in 27 patients [61.4%]. No postoperative deaths occurred. In 5/44 patients [11.4%] the operative specimen was sterilized and in 2/44 patients [4.5%] only very few residual malignant cells difficult to find microscopically were detected. Pathological downstaging was diagnosed in 70.5% [31 out of 44 patient]. Local and distant progression occurred later in 9 patients and the 2-year event-free and overall survival were 83% and 91% at a median follow up time of 20 months. The median event-free and overall survival durations were 12 and 22.5 months respectively. The event-free duration ranged from 5 to 34 months while the overall survival duration ranged from 13 to 36 months. Such a combined preoperative chemoradiotherapy using an oxaliplatin-containing regimen is well tolerated with no increase in surgical morbidity. The rates of pathological downstaging and sphincter-saving surgery are encouraging. Further phase III studies are needed for better evaluation of the value of such regimen

Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer using an oxaliplatin-containing regimen: a phase II study

The combination of radiation. 5-fluorouracil and oxallplatin in locally advanced rectal cancer has been shown to be feasible in phase 1 trials. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting. Between December 2003 and Jan 2006. 46 patients with locally advanced rectal adenocarcinoma entered the study. Radiotherapy was delivered with a four-field technique to a dose of 50.4 Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5 [from days 1-5 and 29-33] in the form of oxalipatin 130 mg/m[2] on day 1 plus 30 minute infusion of 100 mg/m[2] L-folinic acid and continuous infusion of fluorouracil. 350 mg/m[2] for 5 days. Surgery was planned 6 weeks later. All patient completed treatment without modification except 10/46 patients [21.7%] who experienced grade 3/4 toxicity which necessitates treatment interruption and further dose reduction Surgery was performed in 44 patients as 2 cases developed metastasis before the time of the planned surgery. An objective response was seen in 31 patients [6 7.4%]. Sphincter-saving surgery was possible in 27 patients [61.4%]. No postoperative deaths occurred. In 5/44 patients [11.4%]. the operative specimen was sterilized and in 2/44 patients [4.5%]. only very few residual malignant cells difficult to find microscopically were detected. Pathological down staging was diagnosed in 70.5% [31 out of 44 patients]. Local and distant progression occurred later in 9 patients and the 2- year event-free and overall survival were 83% and 91% at a median follow up time of 20 months. The median event-free and overall survival durations were .12 and 22.5 months respectively. The event-free duration ranged from 5 to 34 months while the overall survival duration ranged from 13 to 36 months. - Such a combined preoperative chemoradiotherapy using an oxaliplatin-containing regimen is well tolerated with no increase in surgical morbidity. The rates of pathological down staging and sphincter saving surgery are encouraging. Further phase III studies are needed for better evaluation of the value of such regimen

Mansoura randomized trial: Irinotecan/de gramont regimen versus de gramont regimen alone in chemotherapy naive matastic colorectal carcinoma

The mainstay of treatment for metastatic colorectal carcinoma is chemotherapy. The De Gramont regimen [high-dose leucovorin [LV] and fluorouracil [5-FU] bolus plus continuous infusion every 2 weeks] had been proved to be superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5 day bolus 5-FU/LV regimen in the metastatic state. Irinotecan [CPT-11], a semi-synthetic derivative ofcamp-tothecin, has been shown to exert a cytotoxic action in colorectal carcinoma via the potent and specific inhibition of the nuclear enzyme DNA topoisomerase 1. Investigating the difference in response, toxicity, progression-free and overall survival between the de Gramont regimen alone and the irinotecan plus the de Gramont regimen in the management of cases of metastatic colorectal carcinoma in our locality 160 patients with metastatic colorectal carcinoma were referred mainly from the Gastro Enterology Center [GEC] to both the Clinical Oncology and Nuclear Medicine Department and the Oncology Center of Mansoura University and randomized to receive a 2-hour infusion of LV [200mg/m2/d] followed by a 5-FU bolus [400mg/m2/d] and 22-hour infusion [600mg/m2/d] for 2 consecutive days every 2 weeks, either alone [group A] or together with irinotecan [180mg/m2, 30min intravenous infusion] on day 1 [group B]. Median follow up period was 15 months. Patients allocated to the irinotecan/deGramont regimen had statistically better response rate and symptom amelioration [p=0.04]. Moreover, improvement of patients weight and performance status were statistically better in group B [p=0.03 and 0.02 respectively]. Concerning survival figures, group B had statistically better median progression free survival [8 versus 5 months respectively] and better median overall survival [17 versus 14 months respectively] [p=0.00 and 0.01 respectively]. As regard toxicity, both diarrhea and neutropenia of grade 3 and 4 were more encountered in group B [p=0.004 and 0.003 respectively. free survival were receiving irinotecan, good performance status and normal levels of both hemoglobin and white blood cell count at presentation. On the other hand, independent favorable prognostic factors affecting overall survival were good performance status receiving irinotecan, limited number of metastatic foci and normal levels of hemoglobin, white blood cell count and alkaline phosphatase at presentation. The benefit of adding irinotecan to the de Gramont regimen was reflected positively on all the end points as response, progression-free and overall survival. In addition, the toxicity is generally tolerable and manageable. It is clear that performance status, the number of metastatic foci, and the level of each of hemoglobin, white blood cell count and alkaline phosphatase at time of presentation had their prognostic effect on the course of metastatic colorectal carcinoma

therapeutic outcome of multimodality approach in management of locally advanced, stage III and IVa invasive thymoma

Background: surgery is the treatment of choice for malignant thymoma whenever a complete resection can be accomplished. For locally advanced [LA] and unresectable stage III and IVa thymoma, the therapeutic outcome has been poor

Purpose: to assess tumor response, respectability, event-free survival and, overall survival of multimodality approach in therapy of LA stage III and IVa malignant invasive thymoma

Patients and Methods: fourteen patients [7 males and 7 females] with histologically confirmed invasive thymoma were treated. The median age was 48 years [range: 24-64 years]. Six patients [42.9%] were in clinical stage III disease and, 8 patients [57.1%] had stage IVa disease. The most common histological type was lymphoepithelial [57.1%]. The treatment protocol consisted of 3 courses of induction cisplatin-based chemotherapy [PAC with corticostreoids: cisplatin: 50 mg/m[2] IV DI, doxorubicin: 50 mg/m[2] IV DI, cyclophosphamide: 50 mg/m2 IV DI and, prednisolone: 60 mg/m[2] PO D1-5], then surgery followed by postoperative radiotherapy and completion consolidation chemotherapy; another 3 courses of PAC plus corticosteroids

Results: fourteen patients were enrolled and assessed for response. After induction chemotherapy, complete response encountered in four patients [28.6%], partial response in 7 patients [50%], stable disease in 1 patient [7.1%] and progressive disease in 2 patients [14.3%]. Ten patients [71.4%] performed surgical resection: total resection in 8 patients [57.1%] and, subtotal in 2 patients [14.3%]. 1 refused surgery, 1 patient died with stable disease [7.1%], and 2 patients [lied with progressive disease [14.3%]. At the end of the study and after a median follow-up of 18 months. 11 patients were alive [78.6 %] and 9 patients are event-free [64.3%]. The 3-year calculated actuarial overall and event-free survival of studied patients was 71.3% and 57.1% respectively

Conclusion: Combined treatment approach in management of LA and unresectable invasive thymema is encouraging and demonstrated high objective overall response rates with increased respectability rate and, improvement of overall survival. Preoperative induction chemotherapy followed by surgical resection, postoperative radiotherapy and consolidation chemotherapy may become the standard treatment of LA and unresectable invasive thymoma