Issue 30 cover
Issue No. 30, May 2019

Electronic ISSN 2521-3881

Issue No. 30 - May 2019

Phase II/III Randomized Controlled Trial of Concomitant Hyperfractionated Radiotherapy plus Cetuximab (Anti-EGFR Antibody) or Chemotherapy in Locally Advanced Head and Neck Cancer

Khaled Al-Saleh1, Mustafa El-Sherify1, Reham Safwat3, Amany Elbasmy4, Jitendra Shete1, Amany Hussein1, Marwa Nazeeh5 & Ahmad Bedair 1,5
1 Radiation Oncology Department, Kuwait Cancer Control Centre, Kuwait
2 Clinical Oncology Department, Zagazeg Faculty of Medicine, Egypt
3 Epidemiology and Cancer Registry Department, Kuwait Cancer Control Centre, Kuwait
4 Clinical Oncology department, Tanta Faculty of Medicine, Egypt
5 North West Cancer Center, Londonderry, North Ireland, UK



Introduction: Globally, there is marked variation in overall incidence and presentation of head and neck cancers, these cancers account for 11.5 per 100,000 population in G.C.C states. Concomitant chemotherapy and external beam radiotherapy (EBRT) is indicated in such cancers with aim of organ preservation, control and possible cure. Hyper fractionated radiotherapy with concomitant chemotherapy or cetuximab is a lesser explored option. In this study we wish to assess the tolerability and efficacy of cetuximab with altered fractionation and compare this with the chemotherapy (cisplatin).

Materials & Methods: This is a randomized controlled study from a single institute in Kuwait. Locally advanced head and neck cancer cases excluding cancer nasopharynx are enrolled for the study. Stage III or stage IV-A cases were enrolled with histopathology squamous cell carcinoma. Patients were randomized into 2 arms. Arm A: to receive platinum-based CT i.e. cisplatin in a dose of 100 mg/m2 3-weekly or 40 mg/m2 weekly during radiation; Arm B: received cetuximab with a loading dose 400 mg/m², one week before radiation followed by weekly dose of 250 mg/m² during radiation. Radiotherapy was delivered using intensity modulated radiotherapy (IMRT) or 3D-conformal radiotherapy (CRT). The primary objective was to evaluate whether the use of cetuximab with concurrent hyperfractionated radiation regimen will have loco regional control rates (LC) and Disease-free survival (DFS) that are comparable to concurrent cisplatin in patients with LAHNC. The secondary endpoints were to compare the impact of using concurrent cetuximab vs chemotherapy regimen on Overall Survival of patients (OS) and acute and late adverse events.

Results: From November 2012 to November 2017, 40 patients were randomized. The median age of was 51 years (range 27-72 years). Thirty-five patients are male and remaining was female. 14 patients have their primaries in larynx, 11 in oropharynx, 8 in oral cavity, and 5 has tumor in hypopharynx. Two patients had disease in nasal sinus or overlapping subsides. 50% has T4 lesions while 35% has T3 lesions, Nodal status was (N0-1) in 20 patients and (N2-3) in 20 patients. Overall staging showed a majority to have stage IV disease (63%). HPV was negative in 2 cases in Arm 1 and positive in 2 cases in Arm 2. 22 patients were randomly allocated in Arm A (platinum-based) while 18 were in Arm B (cetuximab). CR was achieved in 59% in arm A vs 50% in Arm B, while PR was 27.3% and 27.8% respectively. Disease progressed in 2 patients in Arm B only. Out of these 40 patients, 14 patients failed (6 and 8 in arm A and B respectively). Locoregional failure was documented in 6 (27.3%) vs 7 (38.9%) of arm A and B respectively, which was statistically not significant possibly related with lower number of cases. 2 years DFS was 56.5% vs 77.3% in cisplatin vs cetuximab arm (denoting nonsignificant increase of relapse rate in cisplatin arm). However, 2 years OS was 80.7% vs 57.3% in cisplatin and cetuximab arm respectively (p value=0.04).

Conclusion: Though cetuximab has lesser side effects but it is not indicated in treatment of LAHNC. Concurrent cisplatin is a trusted option for concomitant setting regardless of the HPV status and tumor location. However, in the context of cisplatin ineligible patients, cetuximab should be used only with hyper fractionation. This preliminary study could represent a good core of large international multicenter RCT.

Keywords: Hyper fractionated radiotherapy, Cetuximab, Locally advanced head neck cancers.

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2 13-21

Betel Chewing: A New Analysis, In Vitro and In Vivo, of the Risk Factors in Oral Cancer


Roberto Menicagli1, Ortensio Marotta2, Maione Nunzia3, Casotti Maria Teresa4
1 RomaBiomedResearch Lab, Italy
2 University Federico II, ENT DEPT, Medicine Faculty, Naples, Italy
3 Urbino Hospital ENT Department, Urbino Italy
4 University of Pisa Radiodiagnostic Med Res


Background: Chewing Betel (areca-nut) can cause oral cancer. This happens when its components are in direct contact with the oral epithelium. The aim of this study is to understand this mechanism by analyzing salivary mucins, in vitro, during and after betel chewing.

Methods: The in vivo analysis would necessarily involve subtraction of betel to understand its effects. This study analyzed the interaction between mucins and betel in vitro. We added increasing amounts of areca powder, and for comparison an equal amount of pure vine tannin to saliva samples provided by a first volunteer. This study analyzes salivary mucins in two volunteers, one of whom is a regular betel consumer, after chewing the areca-nut, on six saliva samples taken at half-hour intervals.

Results: In vitro, total precipitation of the salivary mucins occurs after we added 1g of Areca nut (50 mg Tannin equivalent), a concentration five times lower than what is actually present during the chewing period; in vivo, in the first volunteer, there is a statistically significant increase in the mucins after chewing two and half hours: p-value = 0.02034, while for the regular betel consumer there is a significant decrease: p-value = 0.00512.

Discussion: In vitro, we conclude that the polyphenol content in betel causes total precipitation of mucins and causes poor defense of the oral epithelium. The increase of mucins in the non-routine consumers, show a transient (up to two hours after the end of chewing) inflammatory process. Inflammation can cause keratinization of the oral epithelium because the saliva increases its viscosity for the higher amount of mucins, with its lower adherence and protection of the oral cavity. Subsequent and regular consumption of betel nut, as in the regular betel consumer, can cause chronic fibrosis in the oral epithelium and cut the salivary mucins.

Keywords: Oral cancer, Saliva, Mucins. Tannin

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3 22-28

Retrospective Analysis of Outcomes of Patients with Relapsed, Refractory and Metastatic Sarcomas who have received Metronomic Chemotherapy


Santhosh Kumar Devadas1, Sripad Banavali2
1 Ramaiah Medical College and Hospital, Department of Medical Oncology, Bengaluru, India
2 Tata Memorial Hospital, Department Of medical Oncology, Mumbai, India


Introduction: Paediatric soft tissue sarcoma treatments and outcomes have improved significantly in the last few decades. However, a significant number of patients still succumb to the disease. In low-middle income countries there are dual problems of advanced disease at presentation and financial burden leading to poor compliance to therapy. Hence, we designed a low-cost oral metronomic chemotherapy protocol for these patients and studied the responses and toxicities to therapy in a tertiary referral hospital.

Patients and Methods: This is retrospective, single institutional, observational study. We retrospectively reviewed data of patients with relapsed, refractory or metastatic soft tissue sarcoma (STS) [ Ewing Sarcoma (ES); Rhabdomyosarcoma (RMS) or other STS] who were treated with the metronomic protocol of oral Tamoxifen, Etoposide and Cyclophosphamide (TEC) during the period April 1998 to September 2013, at the Tata Memorial Hospital, Parel, Mumbai. Patients with ES and RMS were primarily treated on our Institutional protocols. The patients included in the analysis were those who had relapsed after the primary protocols and then treated with metronomic TEC protocol; or those with primary refractory or metastatic disease (RMS, ES) and received metronomic TEC therapy.

Results: 49 patients were enrolled. Among the 49 patients, 32 were diagnosed ES, 13 RMS and 4 other STS. For the whole cohort response rates (RR) were 59% and clinical benefit rate (CBR) was 79%. Patients in the study were grouped into the following subgroups. Systemic recurrent/relapsed disease (N=24), metastatic disease at presentation (N=15) and local disease (refractory/recurrent) (N=10). None of the patients required blood or platelet support or admission for supportive care. The PFS for the above groups were 16.8 months, 12.5 months and 126.68 months respectively. This compares favorably with other historical cohorts in a similar setting.

Conclusions: This study provides a preliminary evidence efficacy and tolerability of metronomic chemotherapy in poor risk ES and RMS. It also demonstrates that with this low-cost low risk treatment few patients could go into long term remissions despite high disease burden.

Keywords: STS, Sarcoma, Metronomic, low-income, low-cost

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4 29-32

Does Adjuvant Chemotherapy for Locally Advanced Resectable Rectal Cancer treated with Neoadjuvant Chemoradiotherapy have an impact on survival? A Single Moroccan Institute Retrospective Study


Youssef Seddik, Sami Aziz Brahmi, Said Afqir
Medical Oncology Department, University Hospital Mohammed VI, Oujda, Morocco


Background: In the locally advanced stage, the prognosis of rectal cancer was improved by preoperative chemoradiotherapy and radical surgery including complete total mesorectal excision. At present, the place of adjuvant chemotherapy remains controversial. We aimed to assess the impact of this chemotherapy on our patient survival.

Methods and Materials: This is a retrospective study including patients with locally advanced resectable cancer in the middle and low rectum, treated by neoadjuvant chemoradiotherapy and radical surgery including complete total mesorectal excision at the Medical Oncology Department of the University Hospital Mohammed VI-Oujda, Morocco over a period of six years from January 2007 to December 2012. Patients were divided into two groups: with chemotherapy (Group A) and without it (Group B). In group A, adjuvant chemotherapy was started 4-8 weeks after surgery, constituted of CAPOX (Capecitabine and oxaliplatin) or Capecitabine alone for 8 cycles. We assessed the median overall survival (OS), the median disease-free survival (DFS), the 3-year OS and the 3-year DFS in both groups.

Results: Forty patients were included in this study. Nineteen patients in group A: CAPOX (n= 14), Capecitabine alone (n=5). Twenty-one patients in group B. After a median follow-up of 57 months (range 7-129). Median OS was 94 months in the group A and 119 months in group B [HR = 1.773, 95% CI: 0.759-1.773; P =0.186]. Median DFS was 30 months in group A and 17 months in group B [HR= 1.898, 95% CI: 0.634-5.683; P =0.252]. 3-year OS was 86.4% in group A and 92.5% in group B [HR= 1.549, 95% CI: 0.548- 4.383; p= 0.409]. 3-year DFS was 66.7% in group A and 57.2% in group B [HR=2.166, 95% CI: 0.712- 6.591; p= 0.173].

Conclusion: Although there are some limitations in our study, namely its retrospective design and small size of the cohort, adjuvant chemotherapy for locally advanced resectable rectal cancer treated with neoadjuvant chemoradiotherapy did not improve OS nor DFS.

Keywords: Locally advanced resectable cancer, rectal cancer, adjuvant chemotherapy, overall survival, disease free survival.

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5 33-42

A Multicenter Study of the Impact of Body Mass Index (BMI) on the incidence of Pathologic Complete Response (pCR) Among Saudi Patients with locally advanced Breast cancer (LABC) post Neoadjuvant Chemotherapy (NAC)


Khalid Al-Saleh1, Nashwa Abd El-Aziz1,2, Arwa Ali1,2, Waleed Abo Zeed1,3, Tareq Salah4,5, Sherif Elsamany6,7, Ayman Rasmy8,9,10, Ola ElFarargy8,9, Sufia Husain11, Ammar Al-Rikabi11, Eyad Alsaeed4, Abdurrahman Aldiab1, Ahmed Abd El-Warith1
1 Division of Hematology Oncology, Oncology Center, King Saud University Medical City, King Saud University, Saudi Arabia.
2 Department of Medical Oncology, South Egypt Cancer Institute, Assiut University, Egypt.
3 Department of Clinical Oncology, Mansura University, Mansura, Egypt
4 Radiation Oncology Unit, Oncology Center, King Saud University Medical City,
King Saud University, Saudi Arabia
5 Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Assiut University, Egypt.
6 Department of Oncology, King Abdullah Medical City, Mecca, Saudi Arabia
7 Department of Medical Oncology, Oncology Center, Mansoura University, Mansoura, Egypt
8 Medical Oncology, Zagazig University, Zagazig, Egypt.
9 Adult Oncology Department, Oncology Center, King Fahd Specialist Hospital, Saudi Arabia.
10 Medical Oncology- King Saud Medical City – Riyadh, Saudi Arabia
11 Department of Pathology, King Khalid University Hospital. King Saud University, Saudi Arabia.


Purpose: Obesity was reported to be a poor prognostic factor for breast cancer. There is a growing evidence of increasing prevalence of obesity among Saudi women across all age groups (44%). Since the prognostic significance of obesity was not studied in Saudi patients
with breast cancer, the aim of this study was to evaluate the impact of BMI on pCR in LABC patients post NAC.

Patients and Methods: This is a retrospective study between May 2005 to July 2010; 246 consecutive female patients who were diagnosed of LABC (Stage II & III) and underwent surgery in three tertiary care centers, representative of the Kingdom of Saudi Arabia (King Saud Medical City, Riyadh; King Abdullah Hospital, Mecca and King Fahad Specialist Hospital, Dammam) were included in this study. All included patients have received NAC (Anthracycline/Taxane based combination chemotherapy and ± Herceptin). Patients who were diagnosed to have stage IV breast cancer due to presence of distant metastasis were excluded. Patients were categorized as normal (BMI <25 kg/m2), overweight (BMI of 25 to <30 kg/m2) and obese (BMI >30 kg/m2). pCR was defined as no invasive cancer in the breast or axillary tissue. Univariate and multivariate analysis were used to evaluate the statistical associations between pCR and BMI with respect to the other previously established prognostic factors, namely age, tumor grade, stage, ER/ PR /Her-2neu status, molecular subtypes, and lympho-vascular invasion (LVI).

Results: The median age was 50 years (range 24-68). Molecular subtypes were as follows: luminal A; 23.2%, luminal B; 45.1%, triple negative; 16.7% and Her-2 neu positive; 15%. Infiltrating ductal carcinoma represents the majority of our cohort (92.7%). Eighty-six (35%) were stage II and 160 (65%) were stage III. Intermediate and high-grade malignancies were found in 52% and 44.3% of the patients respectively. Positive lymph vascular invasion was detected in 41.5%. Obese patients constitute 55.7% of our cohort. Pathologic complete response was achieved in 62 patients (25.2%). In Univariate analysis LVI and overweight /obesity were negatively correlated with pCR (P= 0.037 and 0.000 respectively) while tumor grade was positively correlated with pCR (P= 0.008). In multivariate analysis, Overweight/ obesity was the only significant independent factor correlating with pCR (P=0.000). No impact of BMI has been demonstrated on both disease-free survival (DFS) and overall survival (OS) (P=0.93, 0.18 respectively).

Conclusion: In this study, Overweight/Obesity (which represent more than half of the patients =81.3 %) had a negative impact on pCR in Saudi patients with LABC treated with NAC. This poorer outcome in patients with abnormal weight (Overweight/Obesity) necessitates
further prospective studies of this risk factor in order to optimize the care of this group of patients.

Keywords; Body mass index, neoadjuvant chemotherapy, Pathologic complete response locally advanced breast cancer

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6 43-51

Effects of Tualang Honey on Cancer Related Fatigue: A Multicenter Open-label Trial of H&N Cancer Patients


Viji Ramasamy1,2, Norhafiza binti Mat Lazim1, Baharudin Abdullah1, Avatar Singh2
1Department of Otorhinolaryngology - Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kelantan, Malaysia
2Department of Otorhinolaryngology - Head and Neck Surgery, Hospital Taiping, Perak, Malaysia


Introduction: Cancer related fatigue (CRF) is a problem experienced by head and neck cancer patients, especially those who undergo chemoradiation therapy. CRF may persist for years post chemoradiation therapy and significantly impair their quality of life (QOL). Tualang honey is rich in amino acids, vitamins, minerals and enzymes. It is proven to have anti-inflammatory, antioxidant and anti-tumour properties. As CRF is related to inflammatory mediators, the effects of Tualang Honey may improve CRF. The aim of this study is to determine if Tualang honey has a role in improving CRF and quality of life among head and neck cancer patients post chemoradiation.

Methodology: In this open labelled randomized clinical trial, 40 participants aged between 18 and 65 with head and neck cancer who completed chemotherapy and/or radiotherapy in Hospital USM, Kelantan Malaysia or Hospital Taiping were recruited and randomized into two groups: Tualang honey (experimental) group or Vitamin C (control) group. They were prescribed with either daily oral Tualang honey 20mg or vitamin C tablet 100 mg for 8 weeks. Level of fatigue and quality of life were measured using FACIT-Fatigue and FACT H&N questionnaires at baseline, 4 weeks and 8 weeks. The white cell count and C-reactive protein level were also measured at baseline, 4 weeks and 8 weeks.

Results: After four and eight weeks of treatment with Tualang honey or Vitamin C, the fatigue level for experimental group was better than in the control group, and the differences were statistically significant (p<0.05). Statistically significant improvements were seen on quality of life (p<0.05) for the experimental group at week 8, however, no significant improvements were seen in white cell count and C-reactive protein level between control and experimental group.

Conclusion: Our research provided support for the use of Tualang honey to improve CRF and QOL in head and neck cancer patients post chemotherapy or radiotherapy.

Keywords: cancer related fatigue; Tualang honey; quality of life; QOL, C-reactive protein

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7 52-56

The Incidence and Clinical Significance of Atypical Glandular Cells of Undetermined Significance on Cervical Pap Smears


Ehab Al-Rayyan, Mitri Rashed, Maher Maaita, Sultan Qudah, Omar Taso, William Haddadin
Department of Obstetrics and Gynecology, King Hussein Medical Centre, Amman, Jordan.


Objective: To determine the incidence and the association between atypical glandular cells (AGC) reported on cervical pap smears and the underlying malignant and pre-malignant genital tract pathology.

Methods: A retrospective study was performed on the files of women who were had attended our colposcopy clinic at King Hussein Medical Centre (KHMC), between April 2014 and April 2018. Out of 8483 cervical pap smears reviewed, 68 patients have smears reported to be atypical glandular cells of undetermined significance (AGUS). Proper evaluation and follow up was available for 62 patients by performing colposcopic examination, repeating pap smear, proper biopsies and histological results. The factors considered included patients age, parity, symptoms, presence of pregnancy, smoking habits, hormonal therapy usage, colposcopic finding, and histological results of biopsies performed. Data were analyzed and comparison was performed between malignant and pre-malignant lesions.

Results: 68 cases of AGUS pap smears were identified out of 8483 cases reviewed forming incidence of about (0.8%). Of 62 patients with AGUS pap smears, twenty-two cases (32.3%) were found to have clinically significant malignant lesions on subsequent histological follow up. It included 12 cases of endometrial adenocarcinoma, 5 cases of adenocarcinoma of cervix, 3 cases of squamous cell carcinoma of cervix and 2 cases with secondary metastasis to vagina. Of the 62 patients with AGUS pap smears, fourteen cases (20.6%) were found to have pre-malignant lesions. This included 7 cases of endometrial hyperplasia, 3 cases of adenocarcinoma in situ of cervix (ACIS) and 4 cases with cervical squamous intra-epithelial lesions. Abnormal vaginal bleeding was the most common presenting symptom (30.6%); Woman above the age of 40 years and especially post-menopausal were more likely to have significant histological abnormalities.

Conclusion: Though the incidence of AGUS is low, it still important and clinically significant due to high substantial risk of having underlying premalignant or malignant lesions. Colposcopy and directed biopsy, endo-cervical curettage and endometrial biopsy should be performed to all women with AGUC especially to those above the age of 40 years, menopause, or having abnormal vaginal bleeding.

Keywords: Pap smear, atypical glandular cells, cervical neoplasia

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8 57-60

Total or Subtotal Colectomy with Primary Anastomosis for Occlusive Left Colon Cancer: A Safe, Acceptable and Applicable Procedure


William A. Nehmeh, Michel Gabriel, Ahmad Tarhini, Ghassan Chakhtoura, Riad Sarkis, Bassam Abboud, Roger Noun, Cyril Tohmé
Digestive Surgery Department, Hotel Dieu De France University Hospital, Saint Joseph University Faculty of Medicine, Beirut, Lebanon.


Introduction: Occlusive left colon cancer is a major emergency setting in colon cancer with high morbidity and mortality rates. Different surgical treatment exist since there is no clear guidelines for the best treatment. We have conducted this retrospective study in order to evaluate the safety, morbidity, and bowel movement status of the operated patients.

Methods: One-hundred and one left occlusive colon cancer patients were operated of total or subtotal colon resection with primary anastomosis from March 2000 till March 2017 in Hotel Dieu de France hospital. We analyzed the sex ratio, age, caecum condition, tumor localization, number of synchronous adenoma and adenocarcinoma, Dukes stage, major complications and the number of stools per day at 3 and 12 months after surgery.

Results: Mean hospital stay was 7.8 days. Thirteen complications were observed in 11 (10.9%) patients, in which one (1%) patient had splenectomy for severe hemorrhage. Six synchronous adenocarcinoma and 40 adenoma with dysplasia were diagnosed on pathology specimens proximal to occlusion site. Caecum laceration was found in 33 (32.6%) of cases. No patient had anastomotic leak. After 12 months of surgery, the average bowel movement was 2 stools per day.

Conclusion: Our study showed that treating occlusive left colon cancer with total or subtotal colectomy with primary anastomosis is a safe procedure, with a good bowel movement status and presents the advantage to resect an important number of synchronous tumors and adenomas proximal to the occlusion site.

Keywords: Occlusive left colon cancer, total colectomy, primary anastomosis

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9 61-66

Descriptive Study of Nasopharyngeal Carcinoma and Treatment Outcomes: An Eight Years Experience in Hadhramout National Cancer Centre, Yemen


Abdulrahman Ali Bahannan1, Ahmed Mohammed Badheeb2, Samir Yeslam Baothman1
1 Department of Surgical Specialties, Division of ENT, College of Medicine, Hadhramout University, Mukalla, Hadhramout Province, Yemen
2 Professor of Internal Medicine & Oncology and Head of HNCC, College of Medicine, Hadhramout University, Mukalla, Hadhramout Province, Yemen


Objective: To describe the histological patterns, and to evaluate the long-term outcomes of non surgical treatment of nasopharyngeal carcinoma (NPC) in patients registered at Hadhramout National Cancer Centre (HNCC) in Mukalla City, in Hadhramout Province, Yemen.

Methods: Non-randomized descriptive cancer registrybased study of patients with different WHO types of nasopharyngeal cancer and different non surgical treatment modality. Data was obtained from the medical records of patients seen and followed-up at HNCC. Data was collected using Can-Reg 10 computerized program and statistical analysis done using SPSS version-17 software program.

Results: The study included 109 patients with NPC, males were 71(65.14%) and females were 38(34.86%), with a male to female ratio of 2:1. The mean age was 43 (range10-89 years). The majority of the patients were from Hadhramout 85(77.98%), while 24(22.2%) patients were from outside Hadhramout. The most common type of NPC seen according WHO classification was type III 82(75.24%) patients, followed by type II 15(13.76%) patients, and lastly type I 12(11%). The type III tumors of nasopharynx was the predominant type seen in younger patients. Cervical nodal metastasis was found in 86(78.9%) patients, N0 neck was observed in 23(21.1%) patients. The highest annual incidence was observed in 2011 and 2012; fourteen females and 31 males. Patients who underwent curative radiotherapy were 14(12.85%), chemotherapy were 33(30.28%), and concurrent chemoradiotherapy were 62 (56.88%) as initial cancer treatment. Deaths during follow-up period due to local recurrences of NPCs after radiotherapy, chemotherapy and chemoradiotherapy were 1(0.92%), 5(4.59%), 11(10%) respectively. The period of follow-up was 72 months. Two patients were lost from follow-up.

Conclusion: Our results reveal that WHO-NPC type III is the most common type seen in patients, and the predominant type in young males who presented from Hadhramout regions. Treatment outcome was best in irradiated group followed by chemoradiotherapy and lastly chemotherapy.

Keywords: nasopharyngeal carcinoma, incidence, histopathological pattern, treatment outcomes, Hadhramout

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10 67-75

Preoperative Denosumab plus Surgery in the Management of Giant Cell Tumor of Bone: A Comprehensive Narrative Literature Review


Ahmed Abu-Zaid1,2, Sadiq Issa Alaqaili1, Syed Osama Ahmad1, Ibrahim Bin Hazzaa3, Hani Alharbi4
1 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
2 College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America
3 Department of Orthopedic Surgery, King Fahad Medical City, Riyadh, Saudi Arabia
4 Department of Orthopedic Surgery, King Saud Medical City, Riyadh, Saudi Arabia


Giant cell tumor of bone (GCTB) is a biologically benign osteolytic tumor that affects the metaphyseal/epiphyseal portions of bones. Histologically, GCTB is composed of osteoclast-like multinucleated giant cells that express receptor activator of nuclear factor kappa B (RANK), and neoplastic mesenchymal stromal cells that express RANK ligand (RANKL). The pathogenesis of GCTB is primarily attributable to the RANK–RANKL interaction, resulting in the activation of osteoclasts and the resultant osteolytic phenotype. Denosumab is a monoclonal antibody targeted against RANKL. In 2013, it was approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is inoperable, or initial surgery is expected to culminate in substantial morbidity. The aim of this study is to narratively review the current literature on the role of preoperative denosumab followed by surgery in the management of patients with GCTB. In brief, caution should be exercised in the interpretation of existing data on preoperative denosumab in the management of GCTB patients, owing to some critical limitations, for example, short follow-up and only a minority of patients have undergone intralesional surgery following denosumab therapy. All in all, administration of preoperative denosumab is associated with clinical, radiological, and histopathological therapeutic benefits. It is also associated with tolerability, safety, surgical downstaging and less morbid salvageable procedures. Preoperative denosumab does not seem to reduce the likelihood of local recurrence after intralesional therapy; a planned randomized phase III clinical trial (JCOG 1610) will holistically address this concern. Furthermore, more than ten cases of denosumab-related malignant transformation of GCTB have been reported in literature. Lastly, large-sized phase III randomized clinical trials with long-term follow-up data are warranted to withdraw concrete conclusions and

Keywords: preoperative; denosumab; surgery; giant cell tumor of bone; curettage

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11 76-80

Malignant Pleural Mesothelioma: A Multi-Disciplinary Approach


Muhammad Atif Mansha1, Nasir Ali1, Shaukat Ali1, Nausheen Azam2, Agha Muhammad Hammad Khan1
1 Section of Radiation Oncology, Department of Oncology, The Aga Khan University, Karachi, Pakistan.
2 Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, Pakistan


Background: Malignant pleural mesothelioma is a rare disease with poor prognosis. Surgery is used as a radical treatment modality but the risk of local relapse is very high. Therefore, radiation therapy is used in postoperative setting to improve local control. However, owing to elliptical shape, treating the entire pleura requires a large radiation field which increases toxicity. Precision radiation is mandatory to optimally irradiate the tumor area while sparing critical neighboring normal organs.

Case Presentation: A 43-year-old male presented with history of right sided chest pain and cough for 8 months. On further evaluation, he was diagnosed with malignant pleural mesothelioma. The disease was localized but unresectable, therefore a course of neoadjuvant chemotherapy was given. Post chemotherapy, he underwent extra pleural pneumonectomy and the tumor was grossly excised. Histopathology revealed a close resection margin with metastasis in the regional lymph nodes. The case was discussed in multidisciplinary team meeting and adjuvant radiation therapy was offered. The patient was planned with a blend of modern intensity modulated radiation therapy technique and conventional three-dimensional conformal radiation therapy technique, to keep doses of adjacent organs within tolerance limits and at the same time deliver the intended dose of radiation to the tumor site.

Conclusion: Malignant pleural mesothelioma is a lethal disease. Orthodox methods of radiation delivery encompass the entire involved hemi thorax and result in significant morbidity. Highly conformal radiation techniques are preferred to achieve optimal therapeutic ratio at this site. However, despite advances in radiation techniques, current treatment modalities have not significantly made an impact on survival of these patients.

Keywords: Mesothelioma, Intensity modulated radiation therapy, Three-dimensional conformal radiation therapy

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12 81-84

Stage 4S Neuroblastoma: A Report of Two Cases Presenting with Extremes of Biological Behavior


Mohamed Mubarak1, Arbinder Kumar Singal2, Ashok Gawdi3
1 College of Medicine & Medical Sciences, Arabian Gulf University, Kingdom of Bahrain
2 Department of Pediatric Surgery, MGM University of Health Sciences, Kamothe & MGM’s New Bombay Hospital, Vashi, Navi Mumbai
3 MJ Hospitals, Vashi, Navi Mumbai


Neuroblastoma is the most common extracranial solid tumor in childhood. Stage 4S is a special stage of neuroblastoma in which majority of cases may have spontaneous regression; however, in some cases the tumor is rapidly progressive with poor prognosis and thus requires aggressive therapy. Dilemmas in its management and therapy will be discussed. We report two cases of stage 4S neuroblastoma exemplifying these two extreme behaviors. The first case is of a four-month-old baby who initially presented with a thigh lump, labial and foot nodules
as well as hepatic and adrenal involvement. Following the confirmation of stage 4S Neuroblastoma with favorable histology and N-MYC negative amplification, a watchful observation approach was elected. Currently, the patient has completed two years of uneventful follow-ups with normal development. The second case is of a full-term new born baby who presented with abdominal distention and respiratory distress. Stage 4S Neuroblastoma was confirmed with an unfavorable histology and metastasis to the liver and the left adrenal gland. Due to the deterioration of the patient’s condition, chemotherapy with carboplatin and etoposide was initiated for six cycles with a good and rapid response. The patient completed two years of follow up without recurrence.

Keywords: Stage 4s; neuroblastoma; Pepper syndrome; infant

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