The Gulf Journal of

Oncology

ISSUE 17 JANUARY 2015TAblE of CoNTENTS

Original Articles /StudiesImpact of bMI on locoregional Control among Saudi Patients with breast Cancer after breast Conserving surgery and Modified Radical Mastectomy ...................................................................................................................................... 07E.F. Al Saeed, A.J. Al Ghabbban, M.A. Tunio

A statistical quantification of radiobiological metrics in Intensity Modulated Radiation Therapy evaluation ........................ 15A. Surega, J. Punitha, S. Sajitha, BS Ramesh, A. Pichandi, P. Sasikala

A method for assessment of radiation treatment chain of cervical cancer with combined external and brachy radiation therapy ................................................................................................................................................................................ 24A. Chaparian, P. Shokrani

Role of Lymphadenectomy and Its Impact On Survival In Endometrial Carcinoma – An Institutional Experience .............. 30S. Suchetha, P. Rema, S. Vikram, P.S. George, I. Ahmed

Breast Cancer—Epidemiology, Risk Factors and Tumor Profiles in Bangladeshi underprivileged women.............................. 34M. Rahman, A. Ahsan, F. Begum, K. Rahman

Early hematological effects of chemo-radiation therapy in cancer patients and their pattern of recovery- A prospective single institution study ............................................................................................................................... 43H.N. Lee, M.K. Mahajan, S. Das, P. Jeyaraj, J. Sachdeva, M.S. Tiwana

Platinum-based chemotherapy in metastatic triple negative breast cancer: Experience of a tertiary referral centre in India ....................................................................................................................................................................... 52V.V. Maka, H. Panchal, S.N. Shukla, S.S. Talati, P.M. Sha, K.M. Patel, A.S. Anand, S.A. Shah, A.A. Patel, S. Parikh

A Single Institution 18-Years Retrospective Analysis of Malignant Melanoma ............................................................................ 58A. Mukherji, A.K. Rathi, P.K. Mohanta, K. Singh

MRI and ultrasonography for assessing multifocal disease and tumor size in breast cancer: Comparison with histopathological results. ............................................................................................................................................................ 65V. Rudat, A. Nour, N. Almuraikhi, I. Ghoniemy, I. Brune-Erber, N. Almasri, T. El-Maghraby

Patient’s Compliance On the Use of Extended Low Molecular Weight Heparin Post Major Pelvic Surgeries in Cancer Patients at King Hussein Cancer Center ...................................................................................................... 73M. Baba, M. Al Masri, M. Salhab, M. El Ghanem

Can we use Sorafenib for advanced Hepatocellular Carcinoma (HCC) Child Pugh B? ............................................................. 82K. Rasul, A. Elessam, S. Elazzazi, R. Ghasoub, A. Gulied

Case ReportsThe external auditory canal as an unusual site for metastasis of breast carcinoma: A case report ............................................ 85B.A. Baraka, B.J. Al Bahrani, S.S. Al Kharusi, I. Mehdi, A.M. Nada, N.H. Al Rahabi

Primary Mixed Cellularity Classical Hodgkin lymphoma of the Lumbar spine – An unusual presentation ............................ 88K.R. Anila, R. A. Nair, S. Prem, K. Ramachandran

Subdural hematoma during therapy of gastro-intestinal stromal tumor (GIST) with Imatinib mesylate ................................ 92J. Feki, G. Marrekchi, T. Boudawara, N. Rekik, S. Maatoug, Z. Boudawara, M. Frikha

Conference Highlights /Scientific Contribution • Workshop Highlights –The Second Regional Training Of The Trainers’ (TOT) Workshop On Palliative

Care, Kuwait, 23-26 November 2014 ...........................................................................................................................................96• News Notes ....................................................................................................................................................................................102• Advertisements .............................................................................................................................................................................107• Scientific events in the GCC and the Arab World for the 1st Semester of 2015......................................................................108

8282

Can we use Sorafenib for advanced Hepatocellular Carcinoma (HCC) Child Pugh B?

K. Rasul, A. Elessam, S. Elazzazi, R. Ghasoub, A.Gulied

NCCCR, Hamad Medical Corporation, Doha, Qatar

Corresponding Author: Kakil Ibrahim Rasul, CABM, FRCP Edin, ESMO, Senior Consultant Haematology/Oncology, Associate Professor of Clinical Medicine. Weill Cornell Medical College, Qatar; Hamad Medical Corporation, National Center for Cancer Care and Research (NCCCR), P.O. Box 3050, Doha, Qatar

Abstract HCC is the third cause of cancer-related death

worldwide and the fifth most common cancer in the world with an increasing incidence in some areas like Europe, USA and the Gulf region. In this study patients with advanced HCC in both group child pugh A and B were treated with sorafenib.

Methods: This is a retrospective observational study to

assess the safety and effectiveness of sorafenib in patients with advanced HCC child pugh A and B who failed local palliative ablation therapy or were not eligible for such therapy. Forty six patients included.

Results: In both child pugh A and B group the

sorafenib was well tolerated and survival was improved but it was more pronounced in the child pugh A group.

Conclusion:This is the first study that includes high

percentage (47%) of child B group to be treated with sorafenib. Compared with international data there was improved overall survival in both groups.

Key words:Hepatocellular carcinoma, sorafenib,

hepatitis C virus, hepatitis B virus

Introduction Hepatocellular carcinoma (HCC) is an

aggressive tumor accounting for more than 626,000 new cases per year worldwide(1). It has significant mortality because it is often diagnosed late in its course. It is the third cause of cancer related death worldwide and the fifth most common cancer in the world with an increasing incidence in some areas like Europe, USA and the Gulf region (2). HCC generally develops in the contest of chronic liver disease and cirrhosis(3). In the Middle East chronic liver disease is secondary to hepatitis C (HCV) & B (HBV) are the commonest(4). In contrast to USA where alcoholic liver disease is the most common (5), HCC is a heterogeneous disease in terms of etiology as well as clinical presentation and behavior, both the extent of the liver impairment and the advanced tumor state upon diagnosis make the standard treatment with

surgical resection difficult, with median survival of 6 to 20 months (6).

MethodsThis is a retrospective observational study to

assess the safety and effectiveness of sorafenib in patients with advanced HCC who failed local palliative ablation therapy or were not eligible for such therapy. Patients included have been diagnosed with HCC from year 2008 to year 2013. Diagnosis was made by diagnostic radiological imaging criteria either MRI with gadolinum or CT with contrast, few patients required histological confirmation for the diagnosis. All patients were classified according to Child-pugh classification and most of them had chronic liver disease either secondary to hepatitis C or B .The study population consisted of 46 patients with advanced stage of hepatocellular carcinoma. According to Child Pugh Classification, 24 patients were class A and 22 patients class B. 6 patients had liver transplant 4 of them had the transplant for localized HCC then relapsed and treated with sorafenib. Patients have been treated with sorafenib with total oral dose of 800mg/day divided in two daily doses. Around 61% of the patients (28 patients) tolerated

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G. J. O. Issue 17, 2015

the Sorafenib very well , the remaining patients required dose reduction because of side effects as severe diarrhea, hand foot syndrome and elevated liver enzyme and bilirubin. Six patients have skin rash, 9 have diarrhea and 1 patient stopped treatment because of significant liver impairment.

ResultsOur study is a retrospective observational study

and we evaluated patients from May 2008 to December 2013 treated with sorafenib. Data from the total of 48 patients were analyzed, 43 (90%) were males and 5 (10%) were females. Forty-two patients (88%) were non-Qatar and 6 (12%) were Qatari. 46 patients we assessed for survival, 2 patients have insufficient data for assessment. 14 patients lost their follow up (either travelled to their countries or other reasons). Majority of patients received the recommended 800 mg daily dose of sorafenib for both Child-Pugh A (52%) and B (48%). However, the duration of treatment tended to be less for patients with Child-Pugh B. The adverse effects were mainly fatigue, gastrointestinal and dermatological (Table 1). The median overall survival for child-Pugh A was 21.7 months (95% confidence interval 13.1-30.3) and for Child-Pugh B was 9.2 (95% confidence interval 6.7-11.7) with significant difference between the 2 group P value 0.003. Figure (1)

Sorafenib was well tolerated by most of the patients in both Child-Pugh classes with significant improved overall survival, although overall survival was slightly shorter in patients with Child-Pugh B.

Discussion Unresectable HCC is a challenge to manage,

giving the multiple co-morbidities present in these patients. Local treatment options such as trans-arterial chemoembolization (TACE) or radiofrequency ablation (RFA) are not effective for all patients and associated with high recurrence rate (7), making systemic therapy the alternative option for treatment with the new targeted therapy superior to chemotherapy alone in term of overall survival and tolerability (8).

Sorafenib is a multi-targeted tyrosine kinase inhibitor against Vascular Endothelial Growth Factor Receptor (VEGFR 1, 2 and 3) and Platelet-derived Growth Factor Receptor β (PDGFR β) that inhibit tumor angiogenesis (9). Sorafenib has been reported initially in 2007 as a systemic targeted therapy approved for treatment of advanced cases of hepatocellular carcinoma with significant survival benefit over palliative care alone.Figure 1 : Survival curve for patients with child pugh

A and B.

Figure 1 : Survival curve of patients Child-Pugh A an

Table 1. Adverse effects of Sorafenib

84

Sorafenib for advanced HCC Child Pugh B, K. Rasul, et. al.

Patients with unresectable advanced HCC treated with sorafenib have been evaluated in two studies (SHARP and Asia-Pacific). Both phase III studies demonstrated significant improvement in overall survival in these patients with the use of sorafenib. Majority of patients evaluated in both studies were Child-Pugh A (8). In the SHARP study the median overall survival was 10.7 months in the group of patient received sorafenib which are mainly child-Pugh A while in the Asian-Pacific study was 6.5 months and in our study the median overall survival for child-Pugh A was 21.7 months (95% confidence interval 13.1-30.3) and for Child-Pugh B was 9.2 (95% confidence interval 6.7-11.7) with significant difference between the 2 group P value 0.003. Figure (1)

In general clinical trials in HCC include only patients with preserved liver function, as severe liver dysfunction associated with Child-Pugh B or Child-Pugh C status represents a competing cause of death and may confound results (11). Child-Pugh B patients with advanced HCC have been evaluated in GIDEON prospective study

for safety profile, tolerability and overall survival with sorafenib (12). GIDEON has concluded that overall safety profile is similar across Child-Pugh subgroups.

In this study we have evaluated patients with advanced HCC who received sorafenib as systemic therapy between years 2008 – 2013 at our facility in NCCCR - Qatar. We have included patients with Child-Pugh class A and B. Sorafenib was well tolerated by most of the patients in both Child-Pugh classes, the main adverse effect were fatigue, gastrointestinal and dermatological. Compared with international data we have significant improved overall survival, although overall survival was shorter in patients with Child-Pugh B as expected.

ConclusionSorafenib can be used for treatment of advanced

HCC child-Pugh B with good tolerability, but survival was shorter for patient with child-pugh B disease. We need a larger study group to prove the efficacy of this small sample study.

1. Llovet JM, Ricci S, Mazzaferro V, et al; for the SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-390.

2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.

3. David Yiu-Kuen But, Ching-Lung Lai, and Man-Fung Yuen , Hepatocellular carcinoma development in cirrhosis. Best Pract Res Clin Gastroenterol 2007; 21: 161–73:

4. Rasul KI , Al-Azawi S H, Chandra P, Abou-Alfa G, Knuth A, “Status of hepatocellular carcinoma in Gulf region” Chinese Clinical Oncology, Vol 2, No 4 December 2013

5. Jing Gao, Li Xie, Wan-Shui Yang, Wei Zhang, Shan Gao, Jing Wang, Yong-Bing Xiang Risk factors of hepatocellular carcinoma – current status and perspectives.Asian Pac J Cancer Prev 2012; 13: 743–52:

6. Giuseppe M, Silvana E, Ascanio M et al.. , the cancer of liver Italian programme ( CLIP ) investigators A new prognostic system for HCC : a retrospective study of 435 patients , Hepatology 1998;28:751

7. Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology 2004; 127(Suppl 1): S179–S188

8. Ann-Lii Cheng, Yoon-Koo Kang, Zhendong Chen, Chao-Jung Tsao, et al… Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25–34

9. Li Liu, Yichen Cao, Charles Chen, Xiaomei Zhang, Angela McNabola, et al, Sorafenib Blocks the RAF/MEK/ERK Pathway, Inhibits Tumor Angiogenesis, and Induces Tumor Cell Apoptosis in Hepatocellular Carcinoma Model PLC/PRF/5, Cancer Res December 15, 2006 66; 11851

10. National Comprehensive Cancer Network. (NCCN) Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers (Version 2.2013).

11. Ozenne V, Paradis V, Pernot S, Castelnau C, Vullierme MP, Bouattour M, Valla D, Farges O, Degos F. Tolerance and outcome of patients with unresectable hepatocellular carcinoma treated with sorafenib.Eur J Gastroenterol Hepatol. 2010 Sep; 22(9):1106-10.

12. Lencioni R, Kudo M, Ye S-L, Bronowicki J-P, Chen X-P , Dagher L, et al: GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis International Journal of Clinical Practice, May 2014 Volume 68, Issue 5, pages 609–617

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