Table of Contents

Original ArticlesOptimal Management of Acute Lymphoblastic Leukemia (ALL) in Adult Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic ...........................................................................................................................07Ahmad Alhuraiji, Saleem Eldadah, Feras Alfraih, Ramesh Pandita, Ahmad Absi, Amr Hanbali, Mahmoud Aljurf, Riad El Fakih

Combined Intraoperative Radiotherapy (IORT) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreduction Surgery (CRS) as a Novel Approach in the Management of Resectable Pancreatic Cancer ....................................19Ayman Zaki Azzam, Tarek Mahmoud Amin

Peritoneal Carcinomatosis of Colorectal origin in Cyclosporine Immunosuppressed Rats .....................................................................27Elie Rassy, George Hilal, Viviane Track-Smayra, Joseph Kattan, Riad Sarkis, Aline Khazzaka

A Comparative Study of Uninterrupted Treatment by Radiotherapy versus Standard Gap Correction after Interruptions in Oropharyngeal Cancer .............................................................................................................................................31Satya Narayan, Neeti Sharma, Sweta Soni, Rajkumar Niwan

The Frequency and Specific Features of Rare Epidermal Growth Factor Receptor Mutations in Moroccan Patients with Lung Adenocarcinoma whose Tumors harbor positive EGFR mutations ..........................................................40Hind El Yacoubi, Mohamed Lemine Sow, Meryem El Ghouti, Fouad Kettani, Lamia Gamra, Amina Mestari, Lamia Jabri, Ibrahim Elghissassi, Hassan Errihani

Dosimetric Evaluation and Comparison Between Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) Plan in Head and Neck Cancers ..............................................................................45Murugaiyan Nagarajan, Ramesh Banu, Balraj Sathya, Thangavel Sundaram, Thirumalai Palanichamy Chellapandian

Mode of Presentation of Laryngeal Cancer: A Single Radiotherapy Institute Experience in Iraq ............................................................51Shkar Othman Arif, Yousif Ibrahem Al Chalabi, Hiwa Asaad Abdul Kareem, Karzan Marif Murad, Jalil Salih Ali, Sazgar Star Majeed, Shwan Ali Mohammed, Nyan Othman Saeed, Bamo Mohammed Muhsin, Ayah Said, Layth Mula-Hussain

Factors Affecting Survival in Glioblastoma: A 10-year Single-Center Experience from Saudi Arabia ...................................................58Abdullah Azab, Nasser Alsayegh, Omar Kashkari, Suliman Hanbazazah, Yazid Maghrabi, Fahad Alghamdi, Rolina Al-Wassia, Saleh S. Baeesa

Prognostic Impact of Alpha Fetoprotein at Diagnosis on Overall Survival of Single Small Hepatocellular Carcinomas ........................64N. Lahmidani, FZ. Hamdoun, M. Lahlali, H. Abid, M El Yousfi, DA .Benajah, M. El Abkari, SA. Ibrahimi

Clinical Outcomes of Head and Neck Cancer Patients Treated with Palliative Oral Metronomic Chemotherapy at a Tertiary Cancer Center in Kerala, India .......................................................................................................................68Vinin NV, Geetha Muttath, Joneetha Jones, Kalpita Shringarpure, Karthickeyan Duraisamy, Vanitha Priya Deenathayalan, Priya Rathi

Case ReportPrimary Squamous Cell Carcinoma of the Trachea: Two Cases Report ....................................................................................................75Amany Hussein, Khaled Al-Saleh, Mustafa El-Sherify, Hamdy Sakr, Jitendra Shete, Marwa Nazeeh

Bilateral Vocal Cord Immobility After Chemoradiotherapy For Nasopharyngeal Carcinoma ...................................................................80Selvamalar Vengathajalam, Thevagi Maruthamuthu, Nik Fariza Husna Nik Hassan, Irfan Mohamad

Toxic Leukoencephalopathy: An unusual Presentation by 5-Fluorouracil Infusion .................................................................................84Virendra Kumar Meena, Punnet Pareek, Satya Narayan, Sweta Soni

Transformation of Grade I Follicular Lymphoma to Anaplastic Large Cell Lymphoma CD30+ ALK1 - with Complete Response to Brentuximab Vedotin and High-Dose Methotrexate ................................................................................87Mubarak Al-Mansour, Hatim Al-Maghraby, Bader Shirah

Conference Highlights/Scientific Contributions• News Notes .............................................................................................................................................................................................91

• Scientific events in the GCC and the Arab World for 2020 ...................................................................................................................95

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Abstract

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

Case Report

Primary Squamous Cell Carcinoma of the Trachea: Two Cases Report

Amany Hussein1,3, Khaled Al-Saleh1, Mustafa El-Sherify1, Hamdy Sakr1, Jitendra Shete1, Marwa Nazeeh2.

1 Radiation Oncology Department, Kuwait Cancer Control Centre, Kuwait 2 Clinical Oncology Department, Tanta Faculty of Medicine, Egypt

3 Research and Clinical Oncology Department, Medical Research Institute, Alexandria University, Egypt.

Corresponding author: Dr. Mustafa El-Sherify. MBBCh, MSc, MD, Radiation Oncology Dept, Kuwait

Cancer Control Center, Sabah Medical District, Shuwaikh, Kuwait. Email: mustafashawki@yahoo.com

IntroductionPrimary carcinoma of the trachea is uncommon

disease.(1) Nevertheless, most primary cervical tracheal tumours are malignant: namely adenoid cystic carcinoma (ACC), squamous cell carcinoma (SCC), adenocarcinoma, mucoepidermoid carcinoma, carcinoid tumour, and oat cell carcinoma. (2)

Squamous cell carcinoma (SCC) is the most common pathology in smokers while Adenoid Cystic carcinoma (ACC) is more prevalent among non-smokers. The

radiological presentation of these tumors can be intra-luminal, wall-thickening, or exophytic. Endoscopic evaluation reveals that the majority of lesions are bulky and obstructive in nature. (3)

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Case report: Primary Tracheal SCC, Amany Hussein, et. al.

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. Unless the patient presents with blood in the sputum, the initial diagnosis is thought to be bronchial asthma; in many cases. Therefore, suffocation almost always precedes surgical treatment (4).

Bronchoscopy and radiological examination are complementary procedures. The main advantage of imaging is demonstration of tracheal wall thickening and extra-luminal changes. (5)

Persistent or progressive local disease can cause complications such as fatal hemorrhage, oesophago-tracheal fistula, tracheal necrosis, or tracheal stenosis. (6)

Management of tracheal tumors is essentially multidisciplinary. It includes interventional endoscopy, surgery, radiotherapy, and/or endoluminal brachytherapy. Extensive segmental resection of the trachea is the potentially curative treatment of choice for primary lesion. (7)

Post-operative complications are mediastinitis, bilateral pneumonia, and wound-healing disorders. Up to 50% of the trachea can be resected with modern techniques. 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. (8)

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, laryngotracheal resection, cervico-mediastinal exenteration, or carinal resection and reconstruction (9).

The reported 3 and 5-years survival rates are 85.7%, 85.7% for ACC, 64.7% and 26% for SCC, respectively. (4,8)

In 2005, HA Carvalho and colleagues presented their experience with radical high dose-rate endobronchial brachytherapy. They reported a good local control, at the time of the first bronchoscopic assessment. They treated 4 patients with non-resectable tracheal tumour; two patients with SCC died at the 6th and 33rd month after treatment, only the second presented with local recurrence. The other two patients were alive after 64 and 110 months of follow-up (10).

Herein, we are presenting our local experience in treating 2 patients with tracheal primary SCC.

Case 1:60 years old man presented suddenly with

desaturation in the emergency room of the area hospital. Laryngoscopic examination was unremarkable. Patient intubated with difficulty to secure airway. Bronchoscopy showed intraluminal tracheal lesion obstructing lumen more than 70%. Biopsy showed Squamous cell carcinoma (SCC). Radiological investigation was done in form of Computed Tomography (CT) (Figure 1). Surgeons declared unresectable lesion. Bhattacharyya’s staging system was adopted and the case was staged T2N0 (stage II) (11).

Patient received radical radiotherapy first 30 Gy, interim assessment done during radiation; CT and bronchoscopy showed complete mass resolution (figure 2). He was extubated with clear airway. Patient completed radiotherapy a total biological equivalent dose (BED) 60 Gy

Patient kept free of recurrence and alive on last contact at 12 months post-treatment.

Case 2:57 years old male patient complained of chest pain and

tightness. CT neck, chest and abdomen showed tracheal lesion about 4 cm in length, with paratracheal nodal involvement. Bronchoscopy and upper gastrointestinal endoscopy revealed upper tracheal mass, partially

Figure 1. Diagnostic CT showed tracheal lesion (yellow arrowed). Biopsy revealed SCC.

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obstructing the lumen, with no oesophageal lesion noticed. Positron Emitting Tomography (PET-CT) showed significant uptake in the trachea and paratracheal lymph nodes; staged T2N1 (stage IV).(11) (Figure 3).

Patient was treated by radical chemoradiation; radiation with VMAT technique, 64 Gy/32 fractions concurrently with paclitaxel (75mg/m2) and carboplatin (AUC 2) weekly for 7 weeks. Patient showed fair tolerance to the treatment and post treatment assessment by CT showed complete radiological remission. (figure 4)

After 2 months of radiation, patient started to complain of aspiration attacks. Barium swallow study showed tracheoesophageal fistula. Conservative management was adopted but, unfortunately, failed. Feeding tube was inserted and the chest surgeon is planning for fistulae closure.

Discussion and ConclusionBecause of rarity of tracheobronchial tumors, there

have been no randomized controlled trials to determine the optimal therapy. The preferred form of therapy is surgical resection with adjuvant RT because of its favorable

outcomes over RT alone. The reported 5-year survival rate for surgically treated patients is 41.1% for squamous cell carcinoma and 45.7% to adenoid cystic carcinoma (12). Overall, 5-year survival in resected ACC was 52% and unresectable was33% and in resected SCC 5-year survival was 39% while for unresectable cases it was 7.3%. (13)

For patients who are not surgical candidates, the choice of treatment has generally been RT, with few studies describing the use of chemotherapy for tracheal SCC (14, 15). We believe this report is an addition to the existing literature.

Because of advances in surgical techniques, the majority of patients with tracheobronchial cancer are candidates for surgery. Resection of up to one-half of the length of the adult trachea is feasible with modern mobilization techniques (16). Adjuvant radiation is generally recommended for resectable SCC and adenoid cystic carcinoma. (17) Because of the narrow margins of resection achieved in tracheal surgery, Grillo and Mathisen recommended the use of postoperative radiation in all cases, including those with negative margins and lymph nodes. (9)

Figure 2. CT Neck and bronchoscopy showed total resolution of tracheal mass.

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Case report: Primary Tracheal SCC, Amany Hussein, et. al.

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 (12).

Nevertheless, there are some reports about brachytherapy and endotracheal ablation in cases with unresectable disease. (18)

Concurrent chemoradiation in tracheobronchial tumors has few reports. Videtic et al reported one case with tracheal SCC who received 2 cycles of induction cisplatin, etoposide, leucovorin and 5-fluorouracil followed by 2 more cycles concurrent with 60 Gy RT, resulting in survival more than 2 years.(15) Hetna1 et al demonstrated the use of etoposide and cisplatin as consolidation after RT (64Gy) in 4 patients with tracheal cancer, but did not report a median survival rate for those patients.(14) Joshi et al expanded on these results with a recent series of 9 patients treated with radiation (62.5 Gy) concurrent with paclitaxel/carboplatin.(19)

The patients in our report were treated with definitive RT in one patient and with concurrent chemoradiotherapy in the second. We report an overall survival of 18 and 8 months respectively. This appears to be comparable

to the prior reports of SCC treated with definitive RT. However, reported rates of overall survival with definitive RT are difficult to compare because of heterogeneous presentations and a lack of consistent staging in prior reports. Chao et al reported a median survival of only 5.7 months in their cohort (42 patients, 67% SCC) treated with RT alone. Median survival was poorer for patients with lymph node involvement (4.6 months only) (20). Gaissert et al similarly described 5- and 10-year overall survival was 7.3%and 4.9% respectively for patients with unresectable SCC. (13)

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. The most significant reported adverse effect was RTOG grade 2 esophagitis. Neither of our patients required nutritional support via feeding tube during or after therapy (the second patient fixed the tube mainly due to his fistula to reduce chances of aspiration). No pneumonitis was observed in both patients. However, in the second patient tracheoesophageal fistulae developed 2 months after finishing radiation.

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.

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Figure 4. Post treatment CT showing complete remission of tracheal mass (yellow arrow)

Figure 3. Pretreatment CT and PET respectively with tracheal mass in the upper trachea (yellow arrow)

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