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Background: The development and progression of hepatitis B (HBV)-related disease can lead to liver cirrhosis and hepatocellular carcinoma (LC and HCC, respectively). Human leukocyte antigen (HLA) DQ polymorphism has been reported in other recent studies to deal with the association between HBV and liver disease. Our study on the Egyptian population was introduced to assess the strong association between HLA-DQ polymorphism and HBV infection in addition to the progression of HCC. Aim: The aim of this work was to estimate HLA-DQ gene polymorphisms in HBV and HCC. Methods: HLA-DQ genotype polymorphism was assayed by using the ABI Taq Man allelic discrimination assay in different groups in this study. According to the relevant HLA Class II single nucleotide polymorphism (SNP) literature, one single nucleotide polymorphism (SNPs) was selected as the candidate site; it was an HLA-DQ, which showed minor allele frequencies AA, GA, and GG. Results: Haplotype analysis was performed on all the subjects in the study; AA haplotype was the most frequent haplotype in HCC cases (18%) in comparison with HBV and healthy individuals (3%). The haplotype GA was more frequent in the HCC group and slightly more frequent in LC when compared to HBV only cases and also when compared to the control group. In contrast, the GG haplotype was recorded less frequently in HCC individuals, but the HBV and LC groups showed more frequency of this haplotype compared with the HCC group. There was a correlation between AFP serum levels and the frequency of GA and AA polymorphism in HCC cases. Conclusion: We found that AA and GA haplotype was significantly most frequent in HCC. Our findings suggest that HLA-DQ AA and GG polymorphism might serve as a novel potential predictive marker for HCC and may function in tumorigenesis of HBV.

Background:Globally, triple-negative breast cancer (TNBC) is responsible for approximately 15% of all invasive Breast cancer and has been typically associated with poor prognosis. Some retrospective studies have suggested a relatively higher incidence of TNBC in the Middle East and North African Arab countries. Nevertheless, there is complete lack of prospective data, on TNBC in the region, including clinico-pathologic characteristics, treatment patterns and disease outcomes. The TRIPOLI study aims to bridge this information gap.Methods:TRIPOLI is an ongoing prospective multinational, disease registry, designed to recruit 700 newly diagnosed TNBC patients, from 15 institutions within 9 Arab countries: Egypt, Jordon, Morocco, Kingdom of Saudi Arabia, Lebanon, Oman, Kuwait, Qatar and Iraq. This interim analysis includes the patients’ characteristics and treatment approaches of the first 449 cases included in the study from December 2017 to September 2019.Results:All the 449 TNBC patients were females, with a median age of 49 years (range 23.8 - 93.6 years). Premenopausal status was reported in 54.7%, while a positive family history of BC was stated in 25.2% of these cases. 0.2% of patients were below normal (BMI 40 years, patients ≤ 40 years were less likely to be obese (39.4% versus 60.6%; p=0.002), more likely to have grade III tumours (62.3% versus 53.5%; p=0.116), more likely to have T3 or T4 tumours (41.4% versus 32.7%; p=0.038).Conclusion:In this interim analysis, Arab women with TNBC had high parity (≥ 3) and high BMI, compared to existing literature based on western population. High tumor grade, younger age and advanced stages at presentation are in line with similar world-wide reports. Younger women in the Arab region (≤40 years) presented with poor prognostic features, which will be further elucidated in subsequent reports. Citation Format: Hamdy A. Azim, Alaa Kandil, Heba El Zawahry, Hikmat Abdel-Razeq, Hesham Elghazaly, Suad Al Kharusi, Manal M. Abdelwahab, Salah Fayaz, Ahmed Saadeddin, Huda A. Alabdulkarim, Rasha Aboelhassan, Hassan Errihani, Tahseen Al Rubai, Salha Bujassoum Al Bader, Nashwa Mohamed Abdel Aziz, Nagi El Saghir, Giulia Attinà, Ahmed Yosry, Mohamed El Leithy, Loay Kassem, Marwan Ghosn. Triple negative breast cancer prospective registry in middle East and Africa (TRIPOLI) study: Interim analysis of the patients’ characteristics [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-65.

Background: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery in rectal cancer has several adverse effects. Predictive biomarkers for response to nCRT are needed to save patients unnecessary toxicities and to take a timely tailored treatment decision. Epigenetic modifications like DNA methylation patterns have been suspected to be potential predictive biomarkers. Aim: To determine the role of TFAP2E and MLH1 genes’ methylation status and microsatellite instability (MSI) in predicting response to 5-fluorouracil – based nCRT in rectal cancer. Methods: DNA was extracted from 80 patients with newly diagnosed stage II / III rectal cancer. The methylation status of TFAP2E and MLH1 genes was determined by pyrosequencing and MSI was determined using 5 micro­satellite loci by conventional polymerase chain reaction and capillary electrophoresis. Results: The cut-off values for TFAP2E & MLH1 genes’ methylation level were 40% and 15% by receiver operating characteristic curve analysis. Hypermethylated TFAP2E and MLH1 gene promotors and MSI were predominant among non-responders (p

Background Chemoradiation therapy (CRT) has become a primary definitive treatment modality for head and neck squamous cell carcinoma (HNSCC); however, not all patients respond completely to treatment. Ability to identify those patients, who would not achieve complete response, before or early during the course of CRT will allow treatment modifications to improve outcome and overall survival. The aim of this prospective study was to assess the usefulness of diffusion-weighted imaging (DWI) in prediction of early therapeutic response of HNSCC after CRT. Results Local control was achieved in 22 patients out of 46 patients with pathologically proven HNSCC treated by chemoradiation therapy and local failure was detected in 24 patients out of 46 patients. Pretreatment mean apparent diffusion coefficient (ADCpre) was significantly higher in local failure group (1.1 ± 0.2 × 10−3 mm2/s) than local control group (0.89 ± 0.1 × 10−3 mm2/s). An optimal cut-off value of more than 0.94 × 10−3 mm2/s was predictive of local failure with sensitivity 83.33%, specificity 59.9%, PPV 69%, NPV 76.5%. Early intra-treatment percentage change of ADC (ΔADC) was significantly lower in local failure group (21.8% ± 21.3) than in local control group (45.2% ± 27.8). An optimal cut-off value of ≤ 33% was predictive of local failure after CRT with sensitivity of 71.34%, specificity of 60%, PPV of 62.5%, and NPV of 69.2%. Conclusions Diffusion-weighted MRI could be a potential predictive biomarker for therapeutic response of HNSCC to CRT. Primary tumors with higher pretreatment mean ADC, and a smaller early intratreatment percentage increase of mean ADC would be more likely to fail treatment.

PURPOSE Luminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate ( P = .05). CONCLUSION The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Author(s): Guo, Y; Ahn, M-J; Chan, A; Wang, C-H; Kang, J-H; Kim, S-B; Bello, M; Arora, RS; Zhang, Q; He, X; Li, P; Dechaphunkul, A; Kumar, V; Kamble, K; Li, W; Kandil, A; Cohen, EEW; Geng, Y; Zografos, E; Tang, PZ | Abstract: BackgroundTreatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries.Patients and methodsIn this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.ResultsA total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (l1% versus 5%) and leukopenia (0% versus 5%).ConclusionsConsistent with the phase III LUX-Head a Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC.Clinical trial registrationClinicalTrials.gov identifier: NCT01856478.

596 Background: Luminal, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) encompasses the most common subtype of breast malignancies. Neoadjuvant strategies of operable BC are primarily based upon chemotherapy (CT), while neoadjuvant hormone therapy (NAHT) has not been well studied in the Middle East and North Africa (MENA) region. However, these tumors might respond poorly to neoadjuvant CT with significant side effects, emphasizing the need to identify patients who could be candidates for NAHT. Methods: The SAFIA trial is a prospective multicentre, international, double-blind, neoadjuvant phase-III trial using upfront 21-gene Oncotype DX Breast Recurrence Score assay (RS)

Simple Summary Despite the impressive progress in the treatment of triple-negative breast cancer (TNBC), oncologists still face several provocative clinical scenarios in daily practice where clear evidence-based recommendations are lacking, and expert opinion is of utmost importance. In an attempt to seek guidance for these controversial topics in TNBC management, a consensus recommendations session for TNBC was held during the 12th round of the Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020. This special session convened a multidisciplinary committee of 35 panellists who specialize in breast cancer care from 13 countries. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials. Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when >= 75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

This article discusses part of the procedure used to develop the energy requirements in the new green standards for the central district of Al-Madinah city. A comprehensive energy auditing was conducted for sample existing buildings. Two buildings were selected representing both high-end and medium quality typical construction in the district. Field-collected energy use data were used to calibrate energy models to compare the performance of sample buildings with reference buildings complying with ASHRAE 90.1, 2010. It was found that current regulations, the type of ownership in the district, and the increase in utility cost lead to energy performances that matched buildings complying with ST90.1, even though no energy efficiency requirements are currently mandated. These results paved the road for proposing the application of mandatory energy performance regulations to the district that matches international standards and are applicable in the meantime.

Background & Aims: The utility of ultrasound and color Doppler in the diagnosis and evaluation of inflammatory bowel diseases (IBD) has not been studied enough. Therefore, the aim of the current study was to evaluate the importance of conventional abdominal ultrasound and color Doppler in diagnosing IBD and assessing disease activity. Methods: The study was conducted at the National Hepatology and Tropical Medicine Research Institute (NHTMRI) between July 2018 and January 2019, in which 150 patients were suffering from diarrhea, dysentery, tenesmus, or rectal bleeding were evaluated by colonoscopy, high-resolution ultrasound, and color Doppler scans. Results: The present study was conducted on 150 patients; 84 (56%) had ulcerative colitis (UC), 16 (10.7%) had Crohn's disease (CD), and 50 (33.3%) had normal colonoscopy results with a mean age 37.2 ± 9.059. The superior mesenteric Artery Peak Systolic Velocity (SMA-PSV) and End Diastolic Velocity (EDV) were significantly higher in both UC and CD than in the control group; however, pulsatility index (PI) was significantly higher in the control group than both UC and CD. However, there was no significant difference between UC and CD. The inferior mesenteric artery PSV and EDV were significantly higher in both UC and CD than in the control group. Conclusions: Doppler ultrasound findings of SMA and IMA correlate with the incidence of inflammatory bowel disease, the site of disease, and its activity.

594 Background: While hormonal therapy (HT) is a fundamental treatment in breast cancer therapy, neoadjuvant NAHT is not considered standard. The SAFIA trial is a prospective international neoadjuvant Phase III investigating the potential role of the addition of palbociclib (P) in patients (pts) sensitive to HT. We report the results of induction Faslodex (+/- zoladex) in pts initially selected by RS < 31, in order to assess their individual HT sensitivity before double-blind randomization HT vs HT + P followed by surgery. Materials and Methods: A total of 308 pts (stages II and IIIA Luminal A/B HER2 negative) in 24 centers and 6 countries (Middle-East/Maghreb) underwent upfront RS to select pts for induction HT. Pts with RS < 31 received induction neoadjuvant fulvestrant (500 mg i.m Day 1, 14, 28 then q.4 weeks) + goseriline (3.6 mg s.c q.4 w for pre and peri-menopausal pts) for 4 months, followed by clinical and radiological assessment of the disease response before randomization. Response was defined as no progression: Complete Response-CR/ Partial Response-PR: > 50% and Minor Response-MR: < 50% to > 0%/ No Response-NR: progression > 0%. Results: A total of 70 pts (22%) with RS > 31 were excluded, leaving 238 eligible pts for NAHT, age (25-84); pre-peri/ post menopause: 135 (57%)/103 (43%); Luminal A/B: 112 (49%)/114 (51%); Stage II/IIIA: 196 (87%) / 29 (13%). One hundred and seventy-seven pts (177) have validated responses to induction NAHT: CR: 9 pts (5%) / MR: 105 pts (59%) for major response rate: 64% / MR: 56 pts (32%) / NR: 7 pts (4%); available RS 0-10: 23 pts (16%) / RS 11-18: 67 pts (47%) / RS 19-25: 34 pts (24%) / RS 26-30: 18 pts (13%). Correlations between Response to NAHT and RS are shown in the table below (not statistically significant). Conclusions: In our population, upfront Oncotype DX RS < 31 allowed to select pts for induction NAHT without loss of chances with a no-progression rate (CR+PR = MR) of 96%. No significant correlation was found between RS and response to NAHT. Upfront RS > 31 (22%) is selecting pts candidates for neoadjuvant chemotherapy with a potential high risk of endocrine resistance. Clinical trial information: ICRG1201 .

6024 Background: In a previous global phase III trial (LUX-Head & Neck 1), second-line (2L) afatinib significantly improved PFS vs methotrexate (MTX) in pts with R/M HNSCC. Here, we compared efficacy/safety of 2L afatinib vs MTX in Asian pts with R/M HNSCC. Methods: Pts progressing on/after platinum therapy were randomized (2:1) to 40 mg/day afatinib (feeding tube or oral) or 40 mg/m2/week iv MTX. Primary endpoint was PFS by independent review. Secondary endpoints were OS, ORR, and patient-reported outcomes. Results: 340 pts were randomized (afatinib 228, MTX 112). Median (range) duration of treatment (Tx) was 3.0 ( < 0.1–35.9) and 1.4 ( < 0.1–8.8) mos, respectively. Afatinib significantly decreased the risk of progression or death by 37% compared with MTX (HR 0.63; 95% CI: 0.48, 0.82 p = 0.0005, median PFS, 2.9 vs 2.6 mos; landmark analysis at 12 and 24 wks, 58 vs 41%, 21 vs 9%). There was no significant difference in OS (HR 0.88; 95% CI: 0.68, 1.13; median 6.9 vs 6.4 mos). ORR was 28% with afatinib and 13% with MTX (OR 2.8; 95% CI: 1.5, 5.2, p = 0.016). More pts had clinically relevant improvements in global health status/quality of life (GHS/QoL; 40 vs 23%, p < 0.01), swallowing (34 vs 18%, p = 0.01) and pain (34 vs 25%, p = 0.22) with afatinib vs MTX. Post-baseline change in GHS/QoL score was more favorable with afatinib (p < 0.001). Treatment-related adverse events (TRAEs; all/grade ≥3) were reported in 89/16% and 67/23% pts with afatinib and MTX. The most common grade ≥3 TRAEs were rash/acne (4%), diarrhea (4%), and stomatitis (3%) with afatinib, and anemia, leukopenia, and fatigue (all 5%) with MTX. Fatal AEs were reported in 23 and 11% pts with afatinib and MTX. Two ( hypoglycemia, pneumonitis/lung infiltration) and 4 pts had fatal AEs considered related to Tx with afatinib and MTX. 11% and 17% pts discontinued Tx due to TRAEs. Conclusions: LUX-Head & Neck 3 achieved its primary endpoint. Two randomized phase III trials have now demonstrated clinical benefit with 2L afatinib vs MTX. Safety data were consistent with the known tolerability profiles of afatinib and MTX. Clinical trial information: NCT01856478.

Gliomas of the optic pathways are rare childhood central nervous system tumors. The treatment approach is controversial because of its rarity and the slow and unpredictable growth rates of these lesions.We reviewed 50 patients with the diagnosis of optic pathway low-grade gliomas treated between January 1980 and December 1995 at King Faisal Specialist Hospital and Research Center, Saudi Arabia. Thirty-five patients presented with chiasmatic/hypothalamic (posterior tumors), and 15 with optic nerve gliomas with or without chiasmal involvement (anterior tumors). Evidence of neurofibromatosis was present in 18 patients. Twenty-nine patients underwent surgery (total or partial resection), and 12 of these received postoperative radiotherapy (RT). Sixteen patients were treated with primary RT. The radiation dose varied between 42 and 54 Gy (median dose 50).The overall actuarial survival rate was 87.5% at 5 years and 75% at 10 years, and the corresponding progression-free survival (PFS) rates were 69% and 62%. Patients with anterior tumors fared better than those with posterior tumors, with a 10-year PFS rate of 72% and 58%, respectively; the difference, however, was not statistically significant (p = 0.58). A PFS advantage was found in favor of patients with posterior tumors treated with RT (primary or postoperative) compared with no RT, with 5-year PFS rates of 68% vs. 42% (p = 0.03). This, however, did not translate into a survival advantage because of the success of salvage treatment.In multivariate analysis, age (3 vs.3 years) emerged as the only significant determinant for PFS with patients3 years old faring worse (p = 0.03). Neurologic and endocrine dysfunction are significant problems that need to be addressed.

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.

BACKGROUND The pathogenesis of nodular sclerosing Hodgkin disease (HD) has been correlated with Epstein-Barr virus (EBV). The phenotype of lymphocytes in HD and its relations to clinical presentation and to EBV expression have not been characterized fully. Grade II HD is a more aggressive form of the disease. The authors studied cases of HD by flow cytometry (FCM) in an attempt to analyze the phenotype of lymphocytes in the involved lymph nodes and to characterize the phenotype of these lymphocytes in relation to EBV expression, tumor grade, and clinical presentation. MATERIALS AND METHODS The authors prospectively studied lymph nodes from 48 patients with the diagnosis of HD by FCM for T (CD3, CD4, and CD8) and B (CD19) lymphocytes. Ratios of helper to suppressor (CD4 to CD8) and ratios of T to B (CD3 to CD19) lymphocytes were calculated. In situ hybridization for EBV also was performed. The tumors were graded. Clinical data related to age and stage of the disease were retrospectively analyzed. RESULTS There were 30 male and 18 female patients with an age range of 7 to 77 years (median, 17 yrs). EBV expression was seen in 24 (50%) cases. Eleven (23%) cases were classified as Grade II disease. All Grade II cases showed EBV expression, whereas only 13 (39%) cases of Grade I disease were positive (P = 0.03). EBV-positive cases had a median CD4 to CD8 ratio of 1.62, whereas EBV-negative cases had a ratio of 3.86 (P = 0.01). Grade I cases had a median CD4 to CD8 ratio of 4.58, whereas Grade II cases had a ratio of 1.62 (P = 0.007). EBV-positive cases had a median T-lymphocyte to B-lymphocyte ratio of 2.72, whereas EBV-negative cases had a ratio of 3.17 (P = 0.77). Grade I cases had a median T-lymphocyte to B-lymphocyte ratio of 3.51, whereas Grade II cases had a ratio of 1.71 (P = 0.001). A higher percentage of children was seen in the EBV-positive cases than in the negative ones (58% vs. 29%). Cases with low (< 1.5) CD4 to CD8 ratios showed more incidence of high-stage disease (Stages III and IV) than patients with higher ratios (81% vs. 51%). High-stage disease also was seen more frequently in patients with low (< 3) T- to B-lymphocyte ratios (71% vs. 50%). CONCLUSION The authors found that the local immune response in HD may vary from one case to another. The findings also suggest that EBV may play a role in the pathogenesis of the disease in relation to T- and B-lymphocyte response. A more profound immune suppression and decrease in overall T and helper lymphocytes may be seen in aggressive EBV-positive variants of the disease. These changes may impact the initial presentation of the disease and perhaps its overall biologic behavior. Cancer 2001;91:1957–63. © 2001 American Cancer Society.

To identify the prognostic significance of different factors in patients with squamous cell carcinoma of the tongue.Seventy-seven patients with carcinoma of the tongue were treated radically at the King Faisal Specialist Hospital and Research Centre between 1980 and 1989. Twenty patients (26%) were treated by resection alone, 11 (14%) with radiotherapy alone, and 46 (60%) with combined resection and radiotherapy.Forty-seven patients (61%) had T(1-2), 28 (36%) T(3-4), and two T(x) tumours. The regional nodes were clear in 53 (69%) and contained metastases in 24 patients (31%). Thirty patients (39%) developed recurrences, which were local in 9, regional in 14, locoregional in 5, and locoregional with metastatic disease in 2. The five and 10-year overall actuarial survival for all patients were 65% and 53%, respectively, and the corresponding relapse-free survival 56% and 50%. Univariate and multivariate analyses were done of seven variables - age (40 compared with/=40 years), sex, chewing tobacco use, smoking, TNM stage, surgical margins (clear or invaded), and treatment (resection, radiotherapy, or the combination). On univariate analysis chewing tobacco (P=0.04), smoking (P=0.01), invaded resection margins (P=0.04), involved regional lymph nodes (P=0.009), T4 tumours, and patients treated with radiotherapy alone (P=0.001) were associated with poor overall survival. Factors associated with shorter relapse-free survival were age40 (P=0.03), chewing tobacco (P=0.04), invaded resection margins (P=0.01), and smoking (P=0.01). On multivariate analysis, invaded resection margins and smoking (P=0.04)(P=0.02) were associated with shorter overall survival and relapse-free survival (P=0.03 and (P=0.01), while chewing tobacco independently influenced relapse-free survival only (P=0.03).Invaded resection margins and smoking were the only independent prognostic factors that affected both overall and relapse-free survival. Those who chewed tobacco were at high risk of locoregional failure.

Introduction and purpose . Primary Ewing’s sarcoma arising from the bones of the head and neck region is extremely rare representing only 1± 4% of all Ewing’s sarcoma cases. Previous reports suggest a better prognosis for that particular anatomic site. The purpose of this study was to analyze the clinico-epidemiologic characteristics of that rare clinical presentation, as well as its patterns of failure and prognosis following treatment. Materials and methods . This study included a retrospective review of the medical records of patients with the diagnosis of Ewing’s sarcoma of the head and neck region treated at King Faisal Specialist Hospital and Research Center between 1975 and 1996. Results. Out of a total number of 24 cases analyzed, there were 17 males and 7 females with a ratio of 2.4:1.The median age at diagnosis was 16.5 years. A painful swelling was the most common clinical presentation. The maxilla was the most common site of presentation (9/24 cases). There were 3/24 cases who presented with metastatic disease at diagnosis. The majority of patients (16/24 cases) had a tumor size >10 cm. Most patients were treated with systemic chemotherapy plus localized irradiation following an initial biopsy.With a mean follow up of 3.4 years, the 5-year actuarial overall survival (OS) for the whole group was 53%, while the 5-year actuarial disease-free survival (DFS) was 30%. These ® gures were higher than those reported from our institution for young patients ( £ 14 years treated for Ewing’s sarcoma in other anatomic locations (30% v 15%). The response to chemotherapy was the only prognostic factor that affected both the OS and DFS. Conclusion. The prognosis of Ewing’s sarcoma of the head and neck region is slightly better than that of other anatomic sites.The response to systemic chemotherapy is one of the most important prognostic factors affecting both DFS and OS of Ewing’s sarcoma of the head and neck. Multimodality therapy consisting of an initial biopsy, aggressive combination chemotherapy and localized radiotherapy is the treatment of choice for Ewing’s sarcoma of the head and neck region and may result in long-term survival.

Lymphangiomas are very rare benign tumours, believed to arise from congenital malformations of the lymphatic system. They grow very slowly, but are capable of massive expansion and infiltration of the surrounding tissues. If left untreated they can cause serious and sometimes fatal complications. The thorax is commonly affected, with involvement of the ribs, pleura, pericardium, lung parenchyma, mediastinum and vertebrae. Treatment depends on the extent of the disease. While local excision is the treatment of choice for localized lesions, radiotherapy is used for more extensive disease. In this report we describe three patients with extensive thoracic lymphangiomatosis who were treated successfully with irradiation alone. The value of early diagnosis and treatment is emphasized.

Meningiomas are mostly benign but some are atypical or malignant. Surgical resection is curative when complete removal of benign meningiomas is contemplated. Incompletely excised and recurrent tumors are frequently treated with fractionated radiation therapy or stereotactic radiosurgery. The purpose of this study is to evaluate the short-term radiological and functional outcomes of a single center using linear accelerator (Linac) stereotactic radiosurgery for the treatment of intracranial meningiomas. Twenty-nine patients (12 males and 17 females) with 30 meningiomas, in different brain locations (skull base and non-skull base meningiomas), were treated with Linac-based stereotactic radiosurgery. The mean tumor volume was 6.3 cm3, and the mean tumor marginal and maximum doses were 10.9 and 15 Gy, respectively. The median prescribed isodose line was 80%. The patients were followed-up for a minimum of 3 years. Regarding radiological outcome, nine (30%) meningiomas demonstrated evident volume reduction, 19 (63.3%) meningiomas remained unchanged, and two (6.7%) meningiomas increased in size after radiosurgery. The local tumor control rates for skull base meningiomas and non-skull base meningiomas after radiosurgery were 90.9% and 100%, respectively. Regarding functional outcomes, 64% of patients presenting with cranial neuropathies showed improvement of their cranial nerve functions and 29% of patients remained unchanged. One patient had temporary trigeminal neuropathy. Although radiosurgery for meningiomas is generally effective and quite safe in achieving high control rates with minimum morbidity over short- and intermediate-term periods of follow-up, tumor progression might occur in a delayed manner after initial apparent control for few years. We recommend continued follow-up for longer periods to better assess the long-term outcomes.

We collected management information from the 1996 referral documents of 100 consecutive patients who came to us for continued treatment of breast cancer. Major deficiencies were noted with regard to clinical assessment, surgery, and pathology. Since 1997 we have intensified our personnel contacts with referring surgeons, and we have performed outreach visits. To measure the effect of our efforts, we repeated the same collection of information between March 2001 and March 2002. Correct performance of TNM (tumor, node metastasis) classification decreased from 36%–16%. The use of mammography increased from 29%–56%, application of fine needle aspiration (FNA) increased from 46%–70%, and use of core needle biopsy (CNB) increased from 0%–6%. The rate of performance of triple assessment (including correct performance of TNM) was 9% and is now 10%. The number of patients who had surgery before referral decreased from 84%–46%. A proper metastatic work-up in the present study was performed in 10% of patients, and mammography was performed in 33% of the patients who had either modified radical mastectomy (MRM) or breast conserving therapy (BCT). Previously, 78 patients had 98 operations before referral and 75% of those needed additional surgery; now only 9 patients out of 39 who had incisional biopsy or lumpectomy needed further surgery. The median number of lymph nodes now is 10, whereas previously 42% of the axillary dissections yielded < 8 lymph nodes. Pathology reports mentioning both tumor size and surgical margins have increased from 29%–53%. These new data indicate that there is a need to join all hospitals in a national guidelines plan for the management of breast cancer.

Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the King Faisal Specialist Hospital and Research Centre (KFSH & RC) experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. Sixty patients treated at KFSH & RC between 1975 and 1995 were identified, and their records were reviewed retrospectively. Eight patients who had stage III or IV disease, low grade, or did not complete their prescribed treatment were excluded from the study. There were 38 female and 14 male patients with a median age of 59.5 years at the time of diagnosis (range: 10-87 years). Thirty-five of the 52 patients underwent diagnostic partial or total thyroidectomy at other institutions based on a preoperative assumption of thyroid carcinoma. All 52 patients had non-Hodgkin's lymphoma of intermediate (94%) or high (6%) grade. Detailed staging was carried out in all patients; 16 patients (31%) had disease confined to the thyroid gland (stage IE), whereas 36 (69%) had associated disease in cervical lymph nodes and/or the mediastinum (stage IIE) disease. All patients were treated with curative intent. A total of 18 patients (35%) were treated with a single-modality treatment--radiotherapy alone in 2, chemotherapy alone in 13, and surgery alone in the remaining 3 patients. The majority of patients (34/52; 65%) were treated with a combined-modality approach. The overall relapse-free survival (RFS) and overall survival (OS) at 5 years were 72% and 88%, respectively. There were no significant differences in outcome between those treated with single-modality and those with combined-modality therapy. A univariate analysis showed that the presence of mediastinal lymph node involvement was the most important prognostic factor affecting both RFS and OS. Patients with Hashimoto thyroiditis and without "B" symptoms were found to have a significantly higher RFS without influence on the OS. However, patients who had a good performance status (PS) of 0, 1, and 2 were found to have a significantly higher overall survival in comparison to those with poor performance status. Age, sex, stage, histology, lactic acid dehydrogenase level, tumor bulk, and the treatment modality were not found to correlate with RFS or OS. Mediastinal involvement and PS were found to be the most important independent prognostic factors influencing RFS and OS.

Purpose Whole-body fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) scanning has been useful in the management of breast cancer. However, F-18 FDG uptake sometimes has been associated with benign breast disease. Four cases are reported of F-18 FDG breast uptake caused by infectious or inflammatory mastitis that mimics malignant disease. Methods and results Two women had F-18 FDG whole-body scans for the evaluation of a large breast mass after inconclusive results of ultrasonography. In both cases, intense focal F-18 FDG breast uptake was noted that mimicked breast cancer. Histologic examination showed, in one patient, chronic granulomatous infiltration that likely represented tuberculous mastitis, because she showed a good clinical response to empirical anti-tuberculous treatment. The second patient had lactational changes associated with acute inflammation, and the culture grew Staphylococcus aureus. The breast mass completely disappeared 3 weeks after a course of antibiotic treatment. The other two patients had staging F-18 FDG PET scans 1 and 12 months after lumpectomy for breast carcinoma to detect residual, recurrent, or metastatic disease. Both scans showed a ring-like uptake in the involved breast, with superimposed intense focal uptake suggesting tumor necrosis centrally and malignant foci peripherally. In both cases, histologic examination revealed hemorrhagic inflammation secondary to postsurgical hematomas and no evidence of malignancy. Conclusion Acute or chronic infectious mastitis and postsurgical hemorrhagic inflammatory mastitis should be considered in patients who have a breast mass, especially those with a history of tenderness or surgery.

To characterize the patient population and treatment outcomes in patients with Retinoblastoma (RB) referred for External Beam Orbital Radiotherapy (EBORT) to King Faisal Specialist HospitalResearch Centre (KFSHRC), Riyadh, Saudi Arabia from 1976 to 1993.A retrospective study of 120 patients with RB affecting a total of 192 eyes. Patients were divided into three groups. Group A are 60 patients (64 eyes) treated with EBORT to the intact eye to preserve vision. Reese-Ellsworth (RE) Staging was: 1: 12%; 2: 10%; 3: 12%; 4: 23%; and 5: 43%. Twenty-eight patients (47%) also received Vincristine, Adriamycin, and Cyclophosphamide chemotherapy (C/T). Mean follow-up, per patient, was 48.5 months. Standard treatment until 1992 was 45 Gy in 12 fractions of 3.75 Gy, three times weekly over 18 days. Assuming the alpha/beta ratio for early effects and tumor control at 10, Tk = 21 days, Tpot = 5 days, then the Biological Equivalent Dose (BED) was 62 Gy10 for early effects, and 101 Gy3 for late effects. Group B are 28 patients (28 eyes) treated for curative intent with EBORT to the orbit for locally advanced disease, usually after enucleation (24 eyes). Nineteen patients (83%) also had C/T. Mean follow-up was 22.6 months. Group C are 37 patients with advanced disease treated with radiotherapy for palliation. Seventeen (46%) also received C/T. Mean follow-up was 11.7 months.Group A-following EBORT useful vision was retained in RE Stage 1 to 5: 7 of 7, 6 of 6, 4 of 8, 10 of 15, and 7 of 28 eyes, respectively. There was no significant difference between patients who received adjuvant chemotherapy and those who did not. Complications included cataract (27%), retinopathy (25%), vitreous hemorrhage (19%), and orbital deformities (11%). In Group B the local control rate was 71%. In Group C, 10 (27%) of the 37 patients were alive at last contact, and 27 (73%) were either terminal or dead of disease. None of Group A or B patients had positive CSF cytology, bone scan, or bone marrow examination. In Group C 19% had positive CSF cytology, and bone marrow, and 14% had a positive bone scan.1) EBORT preserved useful vision in a significant proportion of patients even in eyes with advanced RE Stage RB, but longer follow-up is likely to reveal an even higher complication rate with this regime. 2) High dose per fraction probably contributed to the increased complications. 3) Chemotherapy did not demonstrate any effect on retaining vision in this study. 4) For disease that is confined to within the eye clinically and radiologically, invasive procedures for CSF cytology, bone marrow examination, and bone scan do not seem warranted. 5) The optimum technique, fractionation, and dosage for RB is still not well defined.

Purpose: Retrospective analysis of patients with medulloblastoma to determine the effectiveness of previous treatments for medulloblastoma and plan for future management strategies. Methods and Materials: During the period March 1976 to December 1991, 172 patients with cerebellar medulloblastoma were referred to King Faisal Specialist Hospital and Research Center. One hundred and forty-nine patients were treated with curative intent. There were six postoperative deaths, and 10 patients planned for radiotherapy treatment failed to complete the prescribed course. One hundred and thirty-three patients completed a course of radiotherapy after surgery. Adjuvant chemotherapy was not used routinely (six patients only). Tumors were staged retrospectively according to the Chang staging system. There were no T1 patients, 32 patients had T2 tumors, 76 had T3 tumors, and 29 had T4 tumors. The T stage could not be allocated in 12 patients. Ninety-nine patients required a shunting procedure either pre- or postoperatively. Forty-six patients had complete resection of tumor, 91 had incomplete resection, and 6 patients had biopsy only. The extent of resection could not be determined in six patients. The median radiation dose for the whole brain was 34 Gy, spine 32.5 Gy, and posterior fossa 52.8 Gy. Fraction sizes ranged from 1.7–1.8 Gy for craniospinal fields and 2 Gy for the posterior fossa boost. Seventy percent completed the prescribed course within 7 weeks. Results: Actuarial survival for the whole group of 149 patients was 53% at 5 years and 38% at 10 years. On univariate analysis, patients with T2 tumors did significantly better as compared to patients with T3 and T4 tumors. Survival of patients who had clinical and radiological complete resection of tumor at surgery was significantly better than patients with incomplete tumor removal. The presence of a ventriculoperitoneal (VP) shunt had a significant negative impact on survival. Treatment failure by site was analyzed with respect to the radiation dose. Doses greater than 50 Gy for the posterior fossa, and greater than 30 Gy for craniospinal axis, resulted in significantly better survival. On multivariate analysis, the only significant prognostic factor was the presence of a VP shunt in patients with T2 tumors. Conclusion: T stage, VP shunt, radiation doses and extent of surgery were important prognostic factors. In this study, radiation doses of more than 50 Gy to the posterior fossa and 30 Gy to the craniospinal axis resulted in improved survival.

RATIONALE AND OBJECTIVES: We compared the effectiveness of pulsed magnetization transfer contrast (MTC) magnetic resonance imaging (MRI) and spin-echo MRI in detecting tumor necrosis. METHODS: Adenocarcinoma cells were transplanted in the livers of 12 syngenic BDIX rats. To induce various degrees of tumor necrosis, the rats were randomly assigned to the following groups: 1) control; 2) localized hyperthermia; 3) intralesional cisplatin; and 4) hyperthermia plus intralesional cisplatin. At day 7 after treatment, the rats were imaged using a 1.5-T imager with 1) multiplanar gradient-recalled echo sequence (MPGR) 500/8/20 degrees with and without magnetization transfer contrast (MTC); 2) spin-echo 2500/20,80, and 3) spin-echo 300/20 pulse sequences. The rats were then sacrificed and pathologic specimens were prepared using MR images as guidance. T2 and ratios of signal intensity after saturation to signal intensity before saturation (Ms/Mo ratios) of the necrotic and granulation tissues and viable tumors were determined in 10 rats. RESULTS: Compared with standard MPGR images, MPGR images with MTC provided better contrast between the pathologic tissues and normal liver. However, T2 values were more useful than Ms/Mo ratios in distinguishing necrotic areas from viable tumor. The T2 values of coagulative necrosis and granulation tissue were significantly different from that of viable tumor. No significant difference between the Ms/Mo ratios of the different pathologic tissues and normal liver was found. CONCLUSION: Pulsed magnetization transfer contrast MRI was inferior to spin-echo MRI in distinguishing necrotic from viable tumors in rat livers using the pulse sequences described, and none of the sequences studied was thought to be reliable enough for this purpose.

Published data from the Middle East and North Africa (MENA) region indicate suboptimal quality of cancer care, while the World Health Organization predicts an increase in cancer cases in developing countries. Major advances in breast cancer management mandate the development of guidelines to improve the quality and efficacy of oncology practice in the MENA region. A Breast Cancer Regional Guidelines Committee was organized and activated, comprising experts from various regional cancer institutions. The multidisciplinary team included 12 medical oncologists, 3 radiation oncologists, 2 radiologists, 2 surgeons, and 1 pathologist. The committee members agreed on adapting the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Breast Cancer for use in the MENA region to achieve common practice standards for treating patients. The members suggested several modifications to the guidelines, especially those related to risk factor profiles. United States-based NCCN experts reviewed these recommendations before final approval. The MENA-NCCN Breast Cancer Guidelines modification process was the first initiative in the development of common practice guidelines in the region. This project may serve as a foundation for the development of evidence-based practice standards, and improve collaborative projects and initiatives.

Summary The neutron therapy program at King Faisal Specialist Hospital and Research Center conducted a phase II study to evaluate the toxicity and efficacy of neutrons against conventional external megavoltage irradiation in patients with locally advanced head and neck malignancy. One hundred and nineteen patients were allocated to receive either photons (46/119) or neutrons (73/119). Radiation effects were scored according to the EORTC/RTOG criteria; data was collected weekly during treatment, once a month for the first year and at 6-month intervals subsequently. While acute effects were scored in all patients, only 59 were evaluable for late effects and locoregional control. A composite of the average reaction results were obtained using this information, to compare them in time, for acute and late effects in both arms of the study, The maximum acute reactions in the two groups were similar. In the majority of the patients (80%) acute skin and mucosal reactions occurred during the last week of treatment. The changes in the subcutaneous tissues and salivary glands became clinically apparent at 3 months or later. Salivary gland toxicity was more severe in the photon arm and the difference was statistically significant at 3 months (P = 0.04) but this was lost at 12 months. Late effects for skin and subcutaneous tissues were significantly more severe in the neutron arm with P values of 0,04 and 0,01 respectively. Three patients in the neutron arm died of grade 4 radiation complications. The local control and survival were similar in both groups.

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).