Publications by authors named "Medhat El Sebaie"

16 Publications

  • Page 1 of 1

Phyllodes tumors of the breast: Adjuvant radiation therapy revisited.

Breast 2021 Apr 7;58:1-5. Epub 2021 Apr 7.

Radiation Oncology Department, National Cancer Institute, Cairo University, Egypt.

Background: Phyllodes tumors (PT) are rare entity and surgical resection is the cornerstone of treatment. No standard of care exists regarding adjuvant treatment especially radiation therapy (RT).

Patients And Methods: We analyzed all patients with non-metastatic, resected phyllodes tumors who presented to our institution from January 2005 through December 2019. Primary study endpoints included local recurrence free survival (LRFS) and overall survival (OS).

Results: One hundred and eight patients were analyzed (patients with incomplete treatment and follow up data were excluded). Fifty patients had benign phyllodes, 26 patients had borderline and 32 patients had malignant phyllodes. In the benign group, no significant difference in LRFS was observed between patients who received adjuvant RT (n = 3) and those who did not (5-year LRFS 100% vs. 85% respectively, p = 0.49). The 5 year OS for patients who received RT was 60% vs. 89% for those who did not (p 0.40). In the borderline/malignant group, adjuvant RT significantly improved five year LRFS (90% in the RT group vs. 42% in the no RT group, p = 0.005). The 5 year LRFS in patients treated with margin negative breast conserving surgery and RT was 100% vs. 34.3% in patients who did not receive RT (p 0.022). Patients treated with mastectomy and RT had a 5 year LRFS of 100% vs. 83% for patients who did not receive RT (p 0.24). On multivariate analysis, radiation therapy was independently associated with decreased hazard of local failure (HR 0.21, CI 0.05-0.89, p = 0.03). No difference in OS was found between the RT and no RT groups (5-year OS was 52% vs. 45% respectively, p 0.54).

Conclusion: The results of the current study confirm the excellent prognosis of benign phyllodes tumors; warranting no further adjuvant treatment after margin-negative surgical resection. For patients with borderline/malignant phyllodes tumors, adjuvant radiation therapy significantly improved LRFS after margin negative wide local excision; however, patients treated with mastectomy did not attain the same benefit from adjuvant irradiation.
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http://dx.doi.org/10.1016/j.breast.2021.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079270PMC
April 2021

Once Daily Versus Twice Daily External Beam Accelerated Partial Breast Irradiation: A Randomized Prospective Study.

Int J Radiat Oncol Biol Phys 2021 Apr;109(5):1296-1300

Radiation Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Purpose: The aim of the current study was to compare toxicity, cosmesis, and local control between the once daily and the twice daily fractionation schemes for external beam accelerated partial breast irradiation.

Methods And Materials: From December 2012 to June 2018, we enrolled 113 patients with ductal carcinoma in situ or invasive breast cancer, node negative disease, and tumors less than 3 cm in size to receive accelerated partial breast irradiation (APBI) to a total dose of 38.5 Gy over 10 fractions given either once (oAPBI) or twice daily (tAPBI). Sixty patients were included in the tAPBI arm and 53 patients were included in the oAPBI arm.

Results: Median follow-up was 74 months (range, 24-105). The median pain score during treatment was 3 out of 10 in the oAPBI and 5 in the tAPBI (P = .001). No differences were observed in GIII early skin toxicity (P = .4) or GI early pulmonary toxicity (P = 1.0) between the 2 treatment arms. GIII late skin toxicity developed in 3.8% and 11.7% of patients in the oAPBI and tAPBI arms, respectively (P = .001). GIII subcutaneous fibrosis developed in 1.9% and 8.3% of patients in the oAPBI and tAPBI, respectively (P = .001). The rate of patients with adverse cosmesis (poor/fair) was 7.5% at 12 months and at 24 months in the oAPBI arm compared with 21.7% and 26.7% in the tAPBI arm (P = .03 and .008, respectively).

Conclusions: oAPBI is a safe, well-tolerated schedule with more favorable outcomes than the tAPBI schedule with regards to late toxicity and cosmesis.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.044DOI Listing
April 2021

Prevalence of Human Papillomavirus (HPV) Infection and the Association with Survival in Saudi Patients with Head and Neck Squamous Cell Carcinoma.

Cancers (Basel) 2019 Jun 13;11(6). Epub 2019 Jun 13.

Department of Pathology & Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.

Head and neck squamous cell carcinoma (HNSCC) shows wide disparities, association with human papillomavirus (HPV) infection, and prognosis. We aimed at determining HPV prevalence, and its prognostic association with overall survival (OS) in Saudi HNSCC patients. The study included 285 oropharyngeal and oral-cavity HNSCC patients. HPV was detected using HPV Linear-Array and RealLine HPV-HCR. In addition, p16INK4a (p16) protein overexpression was evaluated in 50 representative cases. Oropharyngeal cancers were infrequent (10%) compared to oral-cavity cancers (90%) with no gender differences. Overall, HPV-DNA was positive in 10 HNSCC cases (3.5%), mostly oropharyngeal (21%). However, p16 expression was positive in 21 cases of the 50 studied (42%) and showed significantly higher OS ( = 0.02). Kaplan-Meier univariate analysis showed significant associations between patients' OS and age ( < 0.001), smoking ( = 0.02), and tumor stage ( < 0.001). A Cox proportional hazard multivariate analysis confirmed the significant associations with age, tumor stage, and also treatment ( < 0.01). In conclusion, HPV-DNA prevalence was significantly lower in our HNSCC patients than worldwide 32-36% estimates ( ≤ 0.001). Although infrequent, oropharyngeal cancer increased over years and showed 21% HPV-DNA positivity, which is close to the worldwide 36-46% estimates ( = 0.16). Besides age, smoking, tumor stage, and treatment, HPV/p16 status was an important determinant of patients' survival. The HPV and/or p16 positivity patients had a better OS than HPV/p16 double-negative patients ( = 0.05). Thus, HPV/p16 status helps improve prognosis by distinguishing between the more favorable p16/HPV positive and the less favorable double-negative tumors.
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http://dx.doi.org/10.3390/cancers11060820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627701PMC
June 2019

Retraction Note: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers.

Radiat Oncol 2018 04 26;13(1):79. Epub 2018 Apr 26.

Radiation Oncology Section, Oncology Centre, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

The authors are retracting this article [1] because the data have already been published in [2] making this a redundant publication. Ghazi Alsbeih, Najla Al-Harbi, Khaled Al-Hadyan, Mohamed Shoukri and Nasser Al-Rajhi agree with this retraction. Medhat El-Sebaie did not respond to our correspondence.
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http://dx.doi.org/10.1186/s13014-018-1027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918914PMC
April 2018

Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity.

3 Biotech 2014 Apr 26;4(2):137-148. Epub 2013 Apr 26.

Radiation Biology, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Due to individual variations in radiosensitivity, biomarkers are needed to tailor radiation treatment to cancer patients. Since single nucleotide polymorphisms (SNPs) are frequent in human, we hypothesized that SNPs in genes that mitigate the radiation response are associated with radiotoxicity, in particular late complications to radiotherapy and could be used as genetic biomarkers for radiation sensitivity. A total of 155 patients with nasopharyngeal cancer were included in the study. Normal tissue fibrosis was scored using RTOG/EORTC grading system. Eleven candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were selected for their presumed influence on radiosensitivity. Forty-five SNPs (12 primary and 33 neighboring) were genotyped by direct sequencing of genomic DNA. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Results showed statistically significant (P < 0.05) association with radiation complications for six SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). We conclude that these six SNPs are candidate genetic biomarkers for radiosensitivity in our patients that have cumulative effects as patients with severe fibrosis harbored significantly higher number of risk alleles than the controls (P < 0.001). Larger cohort, independent replication of these findings and genome-wide association studies are required to confirm these results in order for SNPs to be used as biomarkers to individualize radiotherapy on genetic basis.
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http://dx.doi.org/10.1007/s13205-013-0135-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964253PMC
April 2014

SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers.

Radiat Oncol 2013 May 22;8:125. Epub 2013 May 22.

Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Background: Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.

Methods: A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).

Results: Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.

Conclusions: Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy.
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http://dx.doi.org/10.1186/1748-717X-8-125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679989PMC
May 2013

HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia.

Infect Agent Cancer 2013 May 4;8(1):15. Epub 2013 May 4.

Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

Background: Cervical cancer incidence is low in Saudi Arabian women, suggesting low prevalence to HPV infection due to environmental, cultural and genetic differences. Therefore, we investigated HPV prevalence and genotype distribution in cervical cancer as well as the association with 9 genetic single nucleotide polymorphisms (SNPs): CDKN1A (p21) C31A, TP53 C72G, ATM G1853A, HDM2 promoter T309G, HDM2 A110G, LIG4 A591G, XRCC1 G399A, XRCC3 C241T and TGFβ1 T10C, presumed to predispose to cancer.

Methods: One hundred cervical cancer patients (90 squamous cell carcinoma and 10 adenocarcinoma) and 100 age/sex-matched controls were enrolled. SNPs were genotyped by direct sequencing and HPV was detected and typed in tumors using the HPV Linear Array Test.

Results: Eighty-two cases (82%) were positive for HPV sequences. Seven HPV genotypes were present as single infections (16, 18, 31, 45, 56, 59, 73) and five double infections (16/18, 16/39, 16/70, 35/52, 45/59) were detected. Most common genotypes were HPV-16 (71%), 31 (7%), and 18, 45, 73 (4% each). Only XRCC1 SNP was significantly associated with cervical cancer (P=0.02, OD=1.69; 95% CI= 1.06-2.66). However, nested analysis revealed a preponderance of HPV-positivity in patients harboring the presumed risk allele TP53 G (P=0.06). Both XRCC1 and TP53 SNPs tended to deviate from Hardy-Weinberg equilibrium (HWE; P=0.03-0.07).

Conclusions: HPV prevalence (82%) in cervical cancer is at the lower range of the worldwide estimation (85 - 99%). While XRCC1 G399A was significantly associated with cervical cancer, TP53 G72C showed borderline association only in HPV-positive patients. Deviation from HWE in HPV-positive patients indicates co-selection, hence implicating the combination of HPV and SNPs in cancer predisposition. Thus, SNPs could be more relevant biomarkers of susceptibility to cervical cancer when associated with HPV infection.
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http://dx.doi.org/10.1186/1750-9378-8-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658889PMC
May 2013

The Role of 18-FDG Positron Emission Tomography (FDG-PET) in Detecting Post- Radiotherapy Loco Regional Relapse/Residual Disease in Nasopharyngeal Cancer.

J Egypt Natl Canc Inst 2009 Dec;21(4):279-85

The Departments of Onoclogy, King Faisal Specialist Hospital & Research Center Riyadh, Saudi Arabia.

Background: Post-radiotherapy nasopharyngeal changes represent a diagnostic dilemma. Early detection of persistent or recurrent disease may be translated to better cure rate if salvage therapy is implemented. Neither clinical exam nor current radiological anatomical studies (CT/MRI) can differentiate between benign post therapy changes and recurrence. PET scan is a functional study capable of identifying viable tumors as areas of increased radiotracer uptake.

Methods: Fifty-five patients underwent 18-FDG PET scans post radiation therapy for nasopharyngeal carcinoma at King Faisal Specialist Hospital and Research Centre. We compared the 18-FDG PET scan with the clinical, radiological and pathological findings.

Results: Clinical examination and CT of the head and neck showed post-treatment abnormality in the nasopharynx in 40 patients. Among these, 28 patients had asymmetry in the CT scan. Three out of the 28 patients had positive PET scan. Out of the 12 patients with positive primary disease in the CT scan, 3 had negative PET scan which was also confirmed by biopsy in 2 patients. Eleven patients had positive PET scan in the primary site; this was pathologically confirmed to be recurrent disease in 5 patients. In 2 patients repeat PET scan was converted to negative. The remaining 4 patients did not have biopsy due to the presence of concurrent distant disease. None of the patients with negative PET scan in the neck exhibit recurrence or persistent neck disease to the day of reporting the study. PET scan showed persistent higher sensitivity, specificity, positive and negative predictive values at both the primary site and the neck region than the CT did.

Conclusion: PET scan is a useful tool in differentiating between post radiotherapy fibrosis and recurrent nasopharyngeal cancer.

Key Words: Nasopharyngeal cancer - FDG/PET - Post therapy changes.
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December 2009

Involvement of mitochondrial DNA sequence variations and respiratory activity in late complications following radiotherapy.

Clin Cancer Res 2009 Dec 17;15(23):7352-60. Epub 2009 Nov 17.

Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Purpose: Mitochondria and ionizing radiation overlap in a number of features; for instance, both generate harmful reactive oxygen species, and that radiation can induce cell death through the intermediary of mitochondria. Because a number of genetic variations in nuclear genes are frequently associated with response to cancer treatment, the aim of this case-control study was to test the hypothesis that mitochondrial DNA (mtDNA) genetic variations can contribute to patient-to-patient variability in normal tissue response to radiotherapy.

Experimental Design: Thirty-two nasopharyngeal carcinomas patients treated with definitive radiotherapy were included. The grade (G) of s.c. and deep tissue fibrosis was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system. Coding and RNA mtDNA (between 611 and 15,978 bp) were sequenced, and genetic variations were scored. Mitochondrial respiratory activity was measured by resazurin reduction assay.

Results: Data showed a significantly (P = 0.003) higher number of nonsynonymous genetic variations in the radiosensitive (G(2)-G(3); 16 patients) as compared with the control (G(0)-G(1); 16 patients) groups. The nonsynonymous A10398G variation in the ND3 gene was significantly associated with fibrotic reaction (P = 0.01). The radiosensitive patients had a 7-fold (95% confidence interval, 1.16-51.65) higher risk of developing moderate to severe fibrosis (G(2)-G(3)) following radiotherapy. This was significantly correlated with lower mitochondrial respiratory activity (P = 0.001).

Conclusion: Mitochondria contribute to radiation sensitivity, and genetic variations can be associated with late reactions to radiotherapy. Predictive markers of radiosensitivity should take into account mtDNA genetic variations in addition to variations in nuclear genes.
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http://dx.doi.org/10.1158/1078-0432.CCR-09-0960DOI Listing
December 2009

Association between XRCC1 G399A Polymorphism and Late Complications to Radiotherapy in Saudi Head and Neck Cancer Patients.

J Egypt Natl Canc Inst 2008 Sep;20(3):302-8

The Departments of Biomedical Physics, King Saud University, Riyadh, Saudi Arabia.

Background: It has been hypothesized that patient to patient variation in normal tissue reactions to radiotherapy is associated with the presence of polymorphic variations in genes involved in DNA repair.

Purpose: To test for a possible association between two single-nucleotide polymorphisms (SNPs), XRCC1 399 G>A Arg/Gln and XRCC3 241 C>T Thr/Met and late reactions to radiotherapy.

Patients And Methods: In this case control study, 50 Head and Neck cancer patients were retrospectively recruited. The grade (G) of fibrosis, a late complication to radiotherapy, was scored using the RTOG/EORTC grading system. Radiosensitive patients with moderate to severe subcutaneous and deep tissue fibrosis (cases, G2-3, n=25) where matched with patients with minimal fibrotic reactions (control, G0-1, n=25). The two nonsynonymous SNPs were genotyped by direct sequencing of DNA extracted from blood or cultured fibroblasts.

Results: Allelic frequency showed significant association with grade of fibrosis for XRCC1 399 G/A (p=0.05), but not for XRCC3 241 C>T (p=0.10).

Conclusions: This pilot study corroborates the association between XRCC1 399 G>A and risk of late normal tissue complications following radiotherapy in our patients. Large studies are required to unravel more SNPs that can influence radiosensitivity and ascertain the associations with reactions to radiotherapy in order to be used as genetic predictive biomarkers of individual radiosensitivity.

Key Words: Single nucleotide polymorphism - Radiosensitivity - Late reactions to radiotherapy - XRCC1 - XRCC3.
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September 2008

Radiosensitivity of human fibroblasts is associated with amino acid substitution variants in susceptible genes and correlates with the number of risk alleles.

Int J Radiat Oncol Biol Phys 2007 May 27;68(1):229-35. Epub 2007 Feb 27.

Radiation Biology Laboratory, Department of Biomedical Physics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Purpose: Genetic predictive markers of radiosensitivity are being sought for stratifying radiotherapy for cancer patients and risk assessment of radiation exposure. We hypothesized that single nucleotide polymorphisms in susceptible genes are associated with, and the number of risk alleles has incremental effect on, individual radiosensitivity.

Methods And Materials: Six amino acid substitution variants (ATM 1853 Asp/Asn G>A, p53 72 Arg/Pro G>C, p21 31 Ser/Arg C>A, XRCC1 399 Arg/Gln G>A, XRCC3 241 Thr/Met C>T, and TGFbeta1 10 Leu/Pro T>C) were genotyped by direct sequencing in 54 fibroblast strains of different radiosensitivity.

Results: The clonogenic survival fraction at 2 Gy range was 0.15-0.50 (mean, 0.34, standard deviation, 0.08). The mean survival fraction at 2 Gy divided the cell strains into radiosensitive (26 cases) and normal (28 controls). A significant association was observed between the survival fraction at 2 Gy and ATM 1853 Asn, XRCC3 241 Met, and TGFbeta1 10 Leu alleles (p = 0.05, p = 0.02, and p = 0.02, respectively). The p53 72 Arg allele showed a borderline association (p = 0.07). The number of risk alleles increased with increasing radiosensitivity, and the group comparison showed a statistically significant difference between the radiosensitive and control groups (p < or = 0.001).

Conclusion: The results of our study have shown that single nucleotide polymorphisms in susceptible genes influence cellular radiation response and that the number of risk alleles has a combined effect on radiosensitivity. Individuals with multiple risk alleles could be more susceptible to radiation effects than those with fewer risk alleles. These results may have implications in predicting normal tissue reactions to radiotherapy and risk assessment of radiation exposure.
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http://dx.doi.org/10.1016/j.ijrobp.2006.12.050DOI Listing
May 2007

Relationship between radiosensitivity and normal tissue complications in Saudi cancer patients treated with radiotherapy.

J Egypt Natl Canc Inst 2004 Dec;16(4):216-23

The Department of Radiation Biology Laboratory, King Faisal Specialist Hospital and Research Centre, Riyadh 11211. Saudi Arabia.

Purpose: To assess the variations in radiosensitivity, its relationship with clinical complications and the potential application of predictive testing in Saudi radiotherapy patients.

Materials And Methods: Forty-one patients included in this study, during (17) or after (24) their radiation treatment for head and neck (26), breast (9), gynecological (3) or other (3) cancer. Skin fibroblasts were established and radiosensitivity was measured. The surviving fraction at 2 Gy (SF2) was calculated and compared to the maximum grade of acute (erythema, desquamation, mucositis, ulceration) and late reactions (atrophy, fibrosis, xerostomia, telangiectasia). Follow-up ranged between 12 and 178 months (median 30).

Results: SF2 ranged between 0.16 and 0.56 (mean 0.34). The inter-patients coefficient of variation (CV) was 26%. The intra-patient CV was 18%. There was a statistically significant correlation between fibroblasts SF2 and the maximum grade of late (p = 0.012; 40 patients), but not acute complications (p = 0.70; 36 patients). There was no correlation between acute and late reactions (p > 0.05; 34 patients).

Conclusions: These data revealed wide variations in cellular radiosensitivity that correlated with late reactions to radiation treatment. Radiotherapy patients, particularly those at risk to sustain severe complications may well benefit from individualizing the doses prescription. However, a predictive test alternative to SF2 is required.
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December 2004

Predictors of outcome after radical cystectomy for bladder cancer in saudi patients; single institution experience.

J Egypt Natl Canc Inst 2004 Sep;16(3):137-44

The Department of Urology, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.

Aim Of The Study: To evaluate different prognostic factors that may affect disease-specific survival in patients with bladder cancer following radical cystectomy.

Methods: Between July 1975 and December 2000, 229 patients underwent radical cystectomy and urinary diversion for bladder cancer in King Faisal Specialist Hospital and Research Center (KFSH & RC), Riyadh, Saudi Arabia. 175 patients had available records for review. Retrospective chart review was done. Demographic, clinical and pathological variables which may affect disease specific survival in bladder cancer patients were pooled. Univariate and multivariate analyses were done with disease specific survival as an end point.

Results: Our patients were 140 males (80%) and 35 females (20%). Their mean age was 54 years (range: 21-90 years). The median follow-up period was 1.5 years (range: one month-19 years). Five-year disease specific survival was 44%. On univariate analysis, patients' age, lymph node status, pathological staging and presence of hydronephrosis were significant predictors of disease specific survival. However, only lymph node status (p<0.0001), pathological staging (p=0.0411) & presence of hydronephrosis (p=0.0264) were significant predictors of disease specific survival in multivariate analysis.

Conclusion: Pathological stage, lymph node status and upper obstructive uropathy are significant prognostic factors in bladder cancer patients after radical cystectomy. These factors may help to define bladder cancer patient groups who require further therapy or enrollment in controlled trials to investigate additional therapy.
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September 2004

Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2005 Jun;62(2):508-13

Division of Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Purpose: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma.

Methods And Materials: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m(2) and epirubicin 70 mg/m(2) on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m(2) for 4 days on Days 42, 63, and 84.

Results: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient received only one induction cycle; all others received two cycles; however, 9 of them required 20% reduction in the second cycle dose. Ninety patients (82%) completed two or more concurrent cycles of cisplatinum. Rates of Grade 3 and 4 reactions after induction chemotherapy were as follows: anemia 1% and 0%, leukopenia 8% and 4%, nausea 27% and 0%, vomiting 25% and 0%, and infection 4% and 4%, respectively. Acute Grade 3 and 4 reactions were also observed during chemoradiotherapy: anemia 1% and 0%, leukopenia 31% and 4%, nausea 35% and 0%, vomiting 26% and 2%, infection in 4% and 2%, mucositis in 49% and 0%, and skin reaction in 39% and 0%, respectively.

Conclusions: Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is a safe and effective method of treatment for locally advanced nasopharyngeal carcinoma. Further investigations in prospective studies are required to evaluate this regimen.
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http://dx.doi.org/10.1016/j.ijrobp.2004.09.050DOI Listing
June 2005

Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a review of etiological features, natural history, and management.

Int J Clin Oncol 2005 Feb;10(1):20-5

Department of Radiation Oncology, National Cancer Institute, Cairo, Egypt.

Squamous cell carcinoma of the urinary bladder, though uncommon in Europe and the United States, is the most common variety of bladder tumor in countries where urinary bilharziasis prevails. A great controversy still exists regarding its natural history and management. Here, we review the literature of bilharzial and nonbilharzial squamous cell carcinoma of the urinary bladder, focusing on large series. Our aim was to gather most of the published data about this disease entity, report it in a systematic comparative review, and attempt to identify the adverse features and variables behind its dismal outcome. The conclusions are that squamous cell carcinoma, whether bilharzial or nonbilharzial, has distinctive clinicopathological features, different from those of the transitional cell variety. These tumors usually present in advanced (muscle-invasive) stages. Pelvic nodal metastases are not common, and the incidence of distant metastases is less than that reported with transitional cell carcinoma. Local treatment, including cystectomy and adjunctive radiotherapy, is the most acceptable way of treating such tumors.
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http://dx.doi.org/10.1007/s10147-004-0457-6DOI Listing
February 2005

Maxillary sinus carcinoma. Natural history and outcome.

Saudi Med J 2004 Jul;25(7):929-33

College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Objective: To assess natural history, treatment outcome and pattern of relapse in patients with maxillary sinus carcinoma.

Methods: A review was conducted of the medical records of all adult patients with maxillary sinus carcinoma, who were treated at King Faisal Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, between January 1990 and December 1999. A total of 60 patients were identified for analysis, 36 men and 24 women; the median age was 58-years (range 23-95). Major presenting symptoms were facial swelling 55%, facial pain 50%, and nasal obstruction 43.4%, with a median duration of 5-months (range 1-24). Histology was squamous cell carcinoma in 71.7% and adenoid cystic in 16.7%. They were restaged according to American Joint Committee on Cancer classification 1997 as II, III and IV in 1, 10 and 49. Thirty patients received treatment with curative intent (surgery in 4 patients, radiotherapy in 2, and combined modality in 24), 6 patients refused treatment and 24 were treated palliatively.

Results: With a median follow up of 50-months (range 2-128) in surviving patients treated with a curative intent, 12/30 failed locally, 4/30 in the regional neck nodes and 2/30 had systemic relapse. The actuarial 5-year overall survival (OS), relapse free survival (RFS) and local control rate (LC) were 55%, 39% and 51%. Treatment modality was the only significant prognostic factor for outcome, with 5 year OS, RFS and LC of 72%, 49% and 61%, for combined modality using surgery followed by radiotherapy compared to 0% for single approach (p=0.0003, p=0.0052 and p=0.0098)

Conclusion: This study indicates that the majority of our patients presented with advanced disease, resulting in poor outcome to conventional treatment modalities. Efforts should be directed to minimize the delay in diagnosis at the primary care level. Combined modality treatment should be offered to all patients with locally advanced disease. New approaches such as neoadjuvant or concurrent chemoradiotherapy with or without surgery need to be considered and evaluated in prospective studies.
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July 2004