Ahmad Alhuraiji¹, Saleem Eldadah², Feras Alfraih³, Ramesh Pandita¹, Ahmad Absi², Amr Hanbali³, Mahmoud Aljurf³, Riad El Fakih³
1 Department of hematology, Kuwait Cancer Control Center, Shuwaikh, Kuwait
2 Adult Hematology/BMT, Princess Noorah Oncology Center, Ministry of the National Guard - Health Affairs, Jeddah, Saudi Arabia.
3 Adult Hematology and HSCT, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common.

Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).

Keywords: Coronavirus, COVID-19; Influenza, acute lymphoblastic leukemia; Pandemic, SARS-CoV-2

Combined Intraoperative Radiotherapy (IORT) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreduction Surgery (CRS) as a Novel Approach in the Management of Resectable Pancreatic Cancer

Ayman Zaki Azzam^1,2 Tarek Mahmoud Amin²
1 General Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Surgical Oncology Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Background: Pancreatic cancer is leading cause of cancer related deaths. The prognosis is usually very poor. In spite of the advances in modern surgery, the outcome is still poor. IORT was recently introduced with recorded improvement in both locoregional tumor control and patient survival. Prophylactic HIPEC was introduced during the initial surgery in order to prevent subsequent peritoneal cancer or tumor recurrence which showed some encouraging results.

Aim of work: Evaluation of the perioperative results of the combination of IORT and HIPEC with CRS as a novel approach in the management of resectable pancreatic cancer.

Patients and Methods: This study was conducted at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. Data were collected retrospectively. A total of five patients were included in the study, during the period from November 2017 to August 2018. All surgeries were done by the same surgeon.

Results: The average age was 51 years (25–63). The patients were two males and three females. All the patients underwent complete surgical resection combined with IORT then HIPEC. All patients were discharged home in good condition. They were regularly followed up without any evidence of local recurrence or metastases.

Conclusion: The combination of IORT and HIPEC with CRS gives the addition of the benefits of each procedure alone without affecting the postoperative morbidity or mortality. This combination appeared to be feasible, safe and well tolerated. However, this need to be applied on a larger number of patients with longer periods of follow-up to reach sound conclusions.

Keywords: Intraoperative radiotherapy (IORT), Hyperthermic intraperitoneal chemotherapy (HIPEC), Cytoreduction Surgery (CRS), Resectable pancreatic cancer

Elie Rassy¹, George Hilal², Viviane Track-Smayra³, Joseph Kattan¹, Riad Sarkis⁴, Aline Khazzaka⁴
1 Department of Hematology-Oncology, Saint Joseph University – Faculty of Medicine, Lebanon
2 Cancer and Metabolism Laboratory, Saint-Joseph University – Faculty of Medicine, Lebanon
3 Department of Pathology, Saint Joseph University – Faculty of Medicine, Lebanon
4 Surgical Research Laboratory, Saint Joseph University, Beirut, Lebanon

Objective: We evaluate the seeding step of peritoneal carcinomatosis cancer as a surrogate for the role of the omentum in colorectal tumors.

Methods: The study included 5 groups of adult male Sprague Dawley rats: immunocompetent rats (group 1), immunosuppressed rats without omentectomy (group 2), immunosuppressed rats with omentectomy (group 3), immunosuppressed rats with omentectomy receiving NSAID (group 4), and immunosuppressed rats without omentectomy receiving NSAID (group 5). Except for group 1, the rats were immunosuppressed using cyclosporine orally at a dose of 25 mg/kg/day that was started 48 hours before tumor cell infiltration in the peritoneum. All the rats received an intraperitoneal suspension of 10 million Caco-2 cancer cells. Rats in groups 1, 2, and 3 were followed up without further interventions and rats in groups 4 and 5 received naproxen 180mg/kg until rat sacrifice. Cyclosporine and naproxen were continued in the corresponding groups until the killing after 21 days of tumor cell infiltration.

Results: Fourteen rats survived the experiment during the observation period and remained in good clinical condition except for one rat (from group 4) that deceased at week 2. At day 21 before sacrifice, mean weight variations showed a +4% in group 0, -9% in group 1, -18% in group 2, -31% in group 3 and -36% in group 4. Light microscopy did not identify any tumor cells in the abdominal cavity or thorax solid organs but showed a granulomatous reaction that involved the majority of the organs.

Conclusion: The conclusions of this study are limited by the small number of rats as it is a pilot study to design an animal model with peritoneal carcinomatosis. Further steps in this study will include more aggressive cancer cell lines such as HT29 and more aggressive immunosuppression in a larger number of rats.

Keywords: peritoneal carcinomatosis; seed and soil; pathophysiology; colon; hematogenous metastasis

A Comparative Study of Uninterrupted Treatment by Radiotherapy versus Standard Gap Correction after Interruptions in Oropharyngeal Cancer

Satya Narayan¹, Neeti Sharma², Sweta Soni¹, Rajkumar Niwan²
1 Department of Radiation Oncology, All India Institute of Medical Sciences, Jodhpur, India
2 Department of Radiation Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute, Bikaner, India

Background: Radiation is an important modality in the treatment of cancer. The longer course of treatment, favors stem cells repopulation, increasing the bulk of stem cells that have to be obliterated. So overall treatment time increases, the chances of local cure by radiotherapy decreases. Primary aim of study is to test the efficacy of radiation treatment after standard correction in unplanned interruption.

Material and Method: 105 patients of head and neck cancer (Oropharynx) with ECOG performance score = 2, with squamous cell carcinoma histopathology and with stage III and IVa were enrolled and 95 patients have completed treatment. Patients were planned for Concurrent chemo-radiotherapy with Cisplatin 40mg/m2 with EBRT (66Gy/33#/2Gy/#) treatment completed in 6.5 weeks. During the treatment the patients were grouped into uninterrupted arm (48) and interrupted arm with standard correction (47).

Results: The enrolled patients mean age: 50 years, males 76.8%, stage IVa disease 50.7%, ECOG performance status (0/1: 67.9%). The complete response (CR) in uninterrupted arm was 64.5% and CR in interrupted arm with standard correction was 61.7% at 6 months (X2= 1.883, p value=0.169). While considering alone Stage IV cases, had found that the locally advanced cases of uninterrupted arm have significant better response (X2= 5.90, p value=0.015). The quality of life was slightly poor, but was statistically insignificant in interrupted arm.

Conclusion: The study concludes that patients with advanced stage (i.e. IVa) have significantly poor treatment outcomes even the standard correction once treatment is interrupted. While the patient treated with gap correction also have similar outcomes in form of disease-free survival and overall survival at 3 years compared to uninterrupted arm.

Keywords: Oropharyngeal cancer, EBRT, Uninterrupted treatment, Standard gap correction

Background: Epidermal growth factor receptor (EGFR) mutations are a heterogeneous group of genetic alterations mainly identified in lung adenocarcinoma (AC). They occur in exon 18 to 20 of the EGFR gene. Common EGFR mutations are deletions in exon 19 and substitutions in exon 21, while mutations in exon 18 and exon 20 are rare. Their response to tyrosine kinase inhibitors (TKI) is different, common EGFR mutations are more sensitive to TKI with better response rate and survival, whereas rare EGFR mutations are TKI resistant with poor prognosis and clinical outcomes. The objective of the present study was to report the frequency and characteristics of rare EGFR mutations in a group of Moroccan patients with lung AC harboring a positive EGFR mutation.

Patients and Methods: All cases of Moroccan patients with lung AC harboring mutated EGFR were collected from 334 EGFR test requested. Common EGFR mutations were defined as deletions in exon 19 and substitutions in exon 21 while mutation in exons 18 and 20 were qualified as rare EGFR mutations. Patients’ characteristics were reported and compared between the two groups of common and rare EGFR mutations.

Results: EGFR mutations were positive in 73/334 of all requested tests. Common EGFR mutations accounted 89% (65/73). Rare EGFR mutations were present in 8 cases (11%). Rare EGFR mutations were composed of 62.5% exon 18 mutations (5/8) and 37.5% exon 20 mutation (3/8). The frequency of regular smokers in patients with tumors expressing rare EGFR mutations was significantly higher than that found in patients with tumors having common EGFR mutations (p=0.013).

Discussion: The frequency found in the present study was consistent with the literature data. However, we found that rare EGFR mutations occurred mostly in exon 18 rather than exon 20, findings that are discordant with the available literature. Thus, we could suggest that Moroccan patients with rare EGFR mutations would benefit more from TKI treatment.

Conclusion: Rare EGFR mutations are a heterogeneous subset of genetic alterations in lung AC. Their study deserves a real relevant interest. Some one tenth of lung AC tumors in Moroccan patients harbor a rare EGFR mutation. Further prospective studies are needed, in larger numbers of patients, to assess their specific characteristics and outcomes.

Keywords: epidermal growth factor receptor, rare mutation, lung adenocarcinoma, Morocco, frequency.

Murugaiyan Nagarajan^1,2, Ramesh Banu², Balraj Sathya², Thangavel Sundaram², Thirumalai Palanichamy Chellapandian²
1 Valvadi Narayanaswamy Cancer Centre, Coimbatore, Tamil Nadu, India
2 G. Kuppuswamy Naidu Memorial Hospital, Coimbatore, Tamil Nadu, India

Aim: To evaluate and compare the dosimetric parameters between volumetric modulated arc therapy (VMAT) and Intensity modulated radiotherapy (IMRT) in head and neck cancers (HNCs).

Material and Methods: A total of 30 patients newly diagnosed with Head and Neck cancers planned for radiotherapy were enrolled in the study. Two plans were made for each patient, one VMAT plan with two complete arcs (one clockwise and another counter clockwise ranging from 181° to 179° (clockwise) and 179° to 181° (counter clockwise) and other seven field IMRT dynamic Plan with beam angles at 0°, 50°, 100°,150°, 210°, 260°, 310°. All plans were generated with 6 MV photons. Optimization and calculations were done in Varian Eclipse planning system.

Results: VMAT plan achieved a better Conformity Index 95% with value of 1.016 ± 0.014 compared to 1.033±0.012 in IMRT. D2%, D5%, D50% were higher in VMAT compared to IMRT. Homogeneity Index was higher for the plans in IMRT with value of 0.035 ± 0.003 compared to 0.058 ± 0.008 with VMAT. The dose to the surrounding organs-at-risk (OARs) are better in VMAT and in particular for brainstem and spinal cord (statistically significant). The monitor units were significantly lower with VMAT (610±70) compared to IMRT (1079± 149).

Conclusion: VMAT achieved acceptable planning target volume coverage with high conformity to the primary tumor and better sparing effect on organs-at-risk particularly spinal cord and brain stem. Statistically significant reduction in monitor units was achieved in VMAT than in IMRT. VMAT should be preferred wherever feasible with due consideration to cost and availability.

Keywords: IMRT, VMAT, Head and Neck Cancers, dosimetry, comparison

Purpose: Laryngeal cancer is relatively common and usually presents with hoarseness due to a lesion in the glottis. We noticed that many of our patients had presented with supraglottic lesions and we could not find local literature in support of this observation. Mode of presentation and site of the lesion of these patients will be addressed in this review.

Materials and Methods: A retrospective cross-sectional descriptive study for laryngeal cancer patients who received radiotherapy at a tertiary radiotherapy center in Iraq, from January 2010 to December 2015, and who are residents in the Sulaimani governorate.

Results: In 6 years, laryngeal cancer patients from Sulaimani were 83 (out of 123 in total), which constituted the most common, 40.8%, head and neck cancers. 86.7% were males and the median age was 68.3 year. Most common presentation was hoarseness, 79.5%, and the least was dysphagia and stridor, 28.9%. Pain and neck swelling were found in 51.8%, 34.9%, respectively. Site of the cancer lesions were in supraglottis in 53%, glottis in 32.5%, transglottis in 8.4%, and subglottis in 6%. Commonest stage was IVA in 54.2% while the least was IVB 2.4%. Squamous cell carcinoma was the pathological type in all of our patients.

Conclusion: Laryngeal cancer is the most common head and neck cancer in our institutional registry. While all the pathologies were of squamous cell carcinoma, hoarseness was the most common presentation and supraglottis was the most common site of involvement.

Keywords: Radiotherapy, Laryngeal cancer, Iraq.

Abdullah Azab¹, Nasser Alsayegh¹, Omar Kashkari¹, Suliman Hanbazazah¹, Yazid Maghrabi¹, Fahad Alghamdi², Rolina Al-Wassia³, Saleh S. Baeesa¹
1 Division of Neurosurgery, Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2 Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
3 Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Background: Glioblastoma is one of the most common and aggressive brain tumors in adults, which is associated with poor survival rate. This study aims to identify the clinical characteristics and outcome of glioblastoma patients who underwent different treatment modalities and to determine the predictors of survival in them.

Methods: A retrospective chart review conducted at King Abdulaziz University Hospital (KAUH). All patients diagnosed histopathologically with glioblastoma, treated between January 2005 and December 2015, were included. The overall survival rate was calculated using the Kaplan-Mayer method. A univariate analysis was carried out using a log-rank test, and the chi-square test was utilized for categorical data.

Results: Thirty-seven patients were included in this study. Age ranged from 5-88 years. 54.1% of the included population were female. Based on immediate postoperative MRI studies, gross total resection was achieved in 40.5%, subtotal resection in 37.8%, and 21.6% underwent biopsy. The majority of patients received adjuvant radiotherapy (56.8%), while 32.5% received adjuvant chemotherapy. The median overall survival was 8.27 months.

Conclusion: Obtained results are consistent with international published reports. Factors that were associated with poor survival were age >50 years, presenting with signs and symptoms of increased intracranial pressure, postoperative KPS <50, and undergoing biopsy.

Keywords: Glioma, glioblastoma, survival, progression, malignancy, academic, chemotherapy, biopsy, gross total resection

Background: Alpha-fetoprotein (AFP) is a serum tumor marker used in the past for surveillance and screening of hepatocellular carcinoma (HCC) in patients with cirrhosis. Its prognostic value is still debated in the literature. The aim of this study was to evaluate the prognostic impact of the AFP rate at diagnosis on the overall survival of patients with a small HCC (<3cm) in patients with cirrhosis.

Patients and methods: Among the 122 patients diagnosed with HCC during the study period, 49 patients had a small HCC at diagnosis, including 40,8% (N 20) patients with a negative AFP (group I) and 59,18% (N 29) with an AFP> 10 ng / ml (group II). Both groups of patients were comparable for age and WHO status (world health organization). Patient survival was assessed by the Kaplan-Meier method. The survival at 5 years was 35.7% in group 1 vs 12.3% in group 2. The AFP level was identified as an independent prognostic factor of survival.

Conclusion: Alpha-fetoprotein serum positivity seems to have prognostic value in patients with single small HCC.

Keywords: small Hepatocellular carcinoma, Alphafetoprotein, survival, prognostic factors

Tracheal squamous cell carcinoma is the most common pathology in smokers while ACC is more prevalent among non-smokers. These tumors tend also to be diagnosed late on account of delayed specific symptoms as hemoptysis, dyspnea, cough, hoarseness, and stridor being the most common.

Management of tracheal tumors is essentially multidisciplinary. It includes interventional endoscopy, surgery, radiotherapy, and/or end luminal brachytherapy.Extensive segmental resection of the trachea is the potentially curative treatment of choice for primary lesion.

The sleeve trachea resection is one of the optimal surgical modalities. The other options are: partial tracheal wall resection and immediate tracheal reconstruction, total laryngectomy plus partial resection of trachea and primary reconstruction, laryngeo-tracheal resection, cervico-mediastinal exenteration, or carinal resection and reconstruction.

Trachea anastomosis is suitable for small defects. The platysma myocutaneous flap combined with the facial flap of the sternohyoid muscle, sternocleidomastoid myoperiosteal flap and the pectoralis major musculocutaneous flap are applied to reconstruct the defects of cervical trachea.

Post-operative radiation therapy, in many cases, is considered a fundamental part of treatment.

Contraindications to surgery include: metastatic disease, invasion of adjacent organs, involvement of airway greater than could be safely resected (i.e. >50% of trachea), involvement of airway that would leave grossly positive margins after resection, spinal kyphosis, or poor medical condition of the patient.

Patients in the current report tolerated therapy well with the use of modern RT techniques and dose delivery to 60 to 64 Gy to a large extent of the central airway.

Additional data and meta-analysis are required to validate the efficacy of chemoradiation in comparison to primary RT alone for unresectable cases and subsequently identify improved systemic therapies. Further investigation into the potential role of additional therapies, such as adjuvant chemotherapy or immunotherapy, may be worth exploring. Our initial findings suggest the use of concurrent chemotherapy in addition to RT in patients with locally advanced tracheal SCC.

Keywords: tracheal SCC, radical chemoradiation, Kuwait

Post chemoradiation vocal cord immobility is a rare complication and this maybe life threatening when patients present with severe aspiration and recurrent pneumonia or even worse if they have an upper airway obstruction. We report a case of nasopharyngeal carcinoma patient whom after receiving curative concurrent chemoradiotherapy, presented with episodes of shortness of breath and aspiration pneumonia finally diagnosed with bilateral vocal cord immobility. She had no evidence of tumour recurrence.

Keywords: Vocal cord, immobility, chemotherapy, radiotherapy, nasopharyngeal carcinoma (NPC).

Background: Toxic leukoencephalopathy predominantly affect white matter of the brain parenchyma. Patient presents either in acute, subacute or chronic phase. The clinical presentation may vary, ranging from mild cognitive impairment to severe neurological dysfunction. It can also mimic psychiatric illness.

Case Report: A 50-year-old woman was diagnosed with locally advanced carcinoma buccal mucosa. She was planned for Neoadjuvant chemotherapy consisting of Docetaxel, Cisplatin, 5-FU (TPF). During 3rd day of 3rd cycle of 5-fluorouracil (5FU) infusion, patient developed hypoactive delirium and later became comatose state of drowsiness, with Glasgow Coma Scale (GCS) was 5. There was no previous history for the same. Hence, the infusion was stopped. Patient was evaluated with NCCT head. No abnormality was seen on CT scan. MRI brain was done and it showed diffusion restriction with T2 / FLAIR hyper intensities in bilateral centrum semiovale, white matter of bilateral parietal region and in corpus callosum. Patient received symptomatic care, nutrition by ryles tube during this period and she started to improve after 1st week of onset of symptoms. After 3 weeks, MRI was repeated and there was complete resolution of previous findings.

Conclusions: Development of neurological symptoms during 5FU infusion is a rare entity. Henceforth, occurrence of toxic leukoencephalopathy should be kept in mind. Diffusion weighted imaging play an important role in both acute episode of toxic encephalopathy and in follow up.

Keywords: Toxic leukoencephalopathy, Diffusion Weighted Imaging, 5-Fluorouracil

Lymphomas are a heterogeneous group of diseases that encompass malignant disorders of B-cells, T-cells, or natural killer cells. B-cell lymphomas represent approximately 80-85% of cases. Transformation of B-cell lymphomas from a low grade to a higher grade within the same lineage is a well-described phenomenon. The most common and well-known transformation is from follicular lymphoma to diffuse large B-cell lymphoma. However, the transformation of B-cell lymphomas to T-cell lymphomas is extremely rare. In this article, we report a case of grade I follicular lymphoma (B-cell lymphoma) that transformed into anaplastic large cell lymphoma CD30+ ALK1- (T-cell lymphoma). This article reported a case with a unique particular combination of morphology and immunophenotype in the same patient. In addition, we report a remarkable response with complete remission following treatment with Brentuximab vedotin (anti-CD30 antibody-drug conjugate) and high-dose methotrexate. The patient achieved this durable response despite the aggressive presentation.

Keywords: Transformation; Follicular Lymphoma; Anaplastic Large Cell Lymphoma; CD30+; Brentuximab Vedotin.