Expression of Glypican-3 is Highly Associated with Pediatric Hepatoblastoma: a Systemic Analysis

Objective: Glypican-3 (GPC3) is reported to be an oncofetal protein that is a useful diagnostic immunomarkerfor hepatoblastoma. However, the results are not inclusive. This study systemically investigated the associationbetween expression of GPC3 and pediatric hepatoblastoma. Methods: Clinical studies evaluating the associationwere identified using a predefined search strategy. GPC3 immunohistochemistry was applied in the pathologicaldiagnosis of hepatoblastoma using the monoclonal antibodies with formalin-fixed and paraffin-embeddedspecimens. Positive predictive rates for the association between expression of GPC3 and pediatric hepatoblastomawere calculated. Results: Specimens from four clinical studies which including 134 patients with pediatrichepatoblastoma tested by GPC3 immunohistochemistry were considered eligible for inclusion. Systemic analysisshowed that, in all patients, pooled positive predictive rate of the association between expression of GPC3 andpediatric hepatoblastoma was 95.5% (128/134). Conclusion: This systemic analysis suggests that the expressionof glypican-3 is highly associated with the diagnosis of pediatric hepatoblastoma.     

Clinical Efficacy and Prognosis Factors for Advanced Hepatoblastoma in Children: A 6-year Retrospective Study

Objective: This study aimed to investigate the effect of multimodality treatment of advanced paediatrichepatoblastoma (HB) and the factors affecting prognosis. Methods: A total of 35 children underwent multimodalitytreatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stemcell transplantation. The patients were followed up every month. Results: Serum AFP levels in 33 out of 35patients in this study were significantly increased (P = 0.0002). According to the statistical scatter plot, the valuesof serum AFP on the 25th, 50th, and 75th percentages were 1,210, 1,210 and 28,318 ng/dl, respectively. Of the35 cases, 21 were stage IV. 18 cases were treated with systemic chemotherapy before surgery, and 3 cases withlocally interventional chemotherapy before surgery. Statistical analysis showed that the preferred interventionaltreatment affected prognosis, and that there was a statistically significant difference (P = 0.024). Some 33patients completed the follow-up, of which 17 were in complete remission (CR), 5 were in partial remission(PR), 1 became disease progressive (DP) , and 10 died. The remission and overall survival rates were 66.7%(22/33) and 69.7% (23/33), respectively. Patients with the mixed HB phenotypes had worse prognoses than theepithelial phenotype (P < 0.001), and patients in stage IV had a lower survival rate than those in stage III (P <0.001). Conclusion: Multimodality treatment can effectively improve remission rate and prolong the survival ofchildren with advanced HB. In addition, alpha-fetoprotein (AFP), a tumor marker of liver malignant tumors,HB pathological classification, and staging are highly useful in predicting prognosis.     

Hepatitis Virus B is Not a Risk Factor in Hepatoblastoma Patients

The prevalence of primary liver cancer varies throughout the world. Hepatoblastoma is the most common pediatric ‍liver malignancy, comprising approximately 1% of all pediatric cancers. The exact etiology of hepatoblastoma remains ‍undetermined. Concerning hepatitis B infection, whether there are links with hepatoblastoma is poorly documented. ‍Here, we summarize knowledge on the prevalence of hepatitis B seropositives among the patients with hepatoblastoma. ‍According to the literature review, six reports were recruited for metanalysis, with a total of 60 cases. The overall ‍prevalence of seropositive cancer was 3.3 % (2/560). Further analysis revealed no correlation between prevalence ‍rate and nationality of the studied population (P > 0.05). Therefore, hepatitis B infection does not appear to be a ‍contributing factor for hepatoblastoma. Further studies are needed to clarify which are the risk factors for the ‍hepatoblastoma.     

Retrospective Analysis of 498 Primary Soft Tissue Sarcomas in a Single Turkish Centre

Background: Soft tissue sarcomas (STS) must be managed with a team involving pathologists, radiologists,surgeons, radiation therapists and medical oncologists. Treatment modalities and demographic charasteristics ofTurkish STS were analysed in the current study. Material-Methods: Primary adult STS followed between 1999-2010 in Cukurova University Medical Faculty Department of Medical Oncology were analzied retrospectivelyResults: Of the total of 498 patients, 238 were male and 260 female. The most seen adult sarcomas wereleomyosarcoma (23%). Localization of disease was upper extremity (8.8%), lower extremity (24.7%), head-neck8.2%, thoracic 8%, retroperitoneal 5.6%, uterine 12.4%, abdominal 10%, pelvic region 3.6 and other regions10%. Some 13.1% were early stage, 10.2% locally advanced, 8.2% metastatic and 12.2% recurrent disease.Patients were treated with neoadjuvant/adjuvant (12%) or palliative chemotherapy (7.2%) and 11.4% patientsdid not receive chemotherapy. Surgery was performed as radical or conservative. The most preferred regimen wasMAID combination chemotherapy in the rate of 17.6%. The most common metastatic site was lung (18.1%). Theoverall survival was 45 months (95%CI 30-59), 36 months in men and 55 months in women, with no statisticallysignificant difference (p=0.5). The survival rates were not different between the group of adjuvant and palliativechemotherapy (respectively 28 versus 18 months) (p=0.06), but radical surgery at 37 months was better than22 months for conservative surgery (p=0.0001). No differences were evident for localization (p=0.152). Locallyadvanced group had higher overall survival rates (72 months) than other stages (p=0.0001). Conclusion: STScan be treated successfully with surgery, chemotherapy and radiotherapy. The survival rates of Turkish peoplewere higher in locally advanced group; these results show the importance of multimodality treatment approachand radical surgery.     

Hepatoblastoma in the Nordic countries

Little is known about the etiology of hepatoblastoma. Because of the young age at diagnosis, several studies have looked at various birth characteristics. The purpose of our study was to investigate the incidence of hepatoblastoma in the Nordic countries and the association between selected birth characteristics and hepatoblastoma. Data from national cancer registries and birth registries in Denmark, Sweden, Norway and Finland 1985-2006 was used. Overall, 155 children with hepatoblastoma aged 0-14 years were included and individually matched to five controls drawn randomly from national population registries. The incidence rate of hepatoblastoma was 1.7 per million person-years with a predominance of boys (1.5:1). Incidence rate was highest before the age of 1 year (8.3 per million person-years). A higher risk of hepatoblastoma was found in children with birth weight <1,500 g [odds ratio (OR) = 9.5; 95% confidence interval (CI): 2.3-38.2], born preterm in week 22-32 (OR = 4.5; CI: 1.8-11.5) and Apgar scores <7 after 1 min (OR = 3.1; CI: 1.3-7.1) and 5 min (OR = 7.5; CI: 1.8-32.4). A doubling in risk was found in children who were large for gestational age (OR = 2.3; CI: 1.0-5.3). No associations were found with birth order, maternal age or maternal smoking. Our study indicates that intrauterine and/or neonatal factors are associated with increased risk of hepatoblastoma. These may include low birth weight and asphyxia leading to neonatal intensive care. Alternatively, the factors may be a consequence of hepatoblastoma developing in utero.     

Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative Analysis on the Tumor Metastasis

Objective: To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) inhepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. Materialsand Methods: Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resectionand confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence ofmetastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NBmetastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastaticgroup (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissueand RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation betweenRECK and MT1-MMP, MMP-14 was analyzed. Results: The metastatic rate of NB was dramatically higher thanthat of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%)was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positiverate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024).The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues hada significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636,P=0.000). Conclusions: In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECKinhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.     

Inflammatory Breast Cancer: a Single Centre Analysis

Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancercharacterized by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d’orangeappearance. It accounts for 1-3% of all newly diagnosed cases of breast cancer in the west. Data on IBC fromIndia are lacking. The aim of our study was to assess the clinical-pathological parameters and outcome of IBCat, All India Institute of Medical Sciences, a large tertiary care centre. Materials and Methods: We screened 3,650breast cancer cases registered from January 2004 to December 2012 and found 41 cases of IBC. Data includeddemographics as well as clinical, radiological and histopathological characteristics, and were collected fromclinical case records using the International Classification of Diseases code (C-50). Patients who presented withIBC as a recurrence, or who had a neglected and advanced breast cancer that simulated an IBC were excludedfrom this study. Results: The median age was 45 years (range 23-66). The median duration of symptoms was5 months. The American Joint Committee on Cancer stage (AJCC) distribution was Stage III - 26 and IV - 15patients. Estrogen receptor (ER), progesterone receptor (PR) positivity and human epidermal growth factorreceptor 2 (HER2/neu) positivity were 50%, 46% and 60%, respectively. Triple negativity was found in 15% of thecases. All the non metastatic IBC patients received anthracycline and/ or taxane based chemotherapy followed bymodified radical mastectomy , radiotherapy and hormonal therapy as indicated. Pathological complete remissionrate was 15%. At a median follow-up of 30 months, the 3 year relapse free survival and overall survival were30% and 40%respectively. Conclusion: IBC constituted 1.1% of all breast cancer patients at our centre. Onethird of these had metastatic disease at presentation. Hormone positivity and Her2 neu positivity were foundin 50% and 60% of the cases, respectively.     

肝癌细胞凋亡中TIP30对Bcl-2蛋白家族的表达的调节

Objective: To investigate the role of TIP30 in the apoptotic signal pathway in HepG2, and Hep3B and Hu-7 hepatoblastoma cell lines. Methods: In order to confirm whether TIP30 conducted Bcl-2 family was involved in apoptosis signal pathway, MTT assay, in situ 3 end labelling of DNA assay and Western blot were carried out to detect the diverse apoptotic function of TIP30 and the regulation of Bcl-2 family. Results: TIP30 induced apoptosis as evidenced by morphological changes in hepatoblastoma cells, which was accompanied by up-regulating Bax and Bad proteins and stimulating them from cytoplasm to mitochondria, and down-regulating Bcl-xl, while it had no effect on the level of Bak protein. Conclusion: TIP30 induced apoptosis partly by modulating the protein levels of members of Bcl-2 family in hepatoblastoma cells. Elucidating the mechanism by which TIP30 induces cell death might establish it as an anticancer factor.     

肝癌细胞凋亡中TIP30对Bcl-2蛋白家族的表达的调节(英文)

目的 TIP30为一新发现的可引起细胞代谢抑制和凋亡的因子。最新研究表明:TIP30可引起 Bcl-2家族的两个促凋亡的成员 Bad和 Bax 的表达升高并抑制小鼠肿瘤生长。本实验的目的在于研究在肝癌细胞系 HepG2、Hep3B 和 Hu-7的凋亡中,TIP30所参与的信号转导途径。方法采用 MTT、原位 DNA 末端标记、免疫印迹法研究 TIP30引起的细胞凋亡及其对 Bcl-2蛋白家族的调节。结果 TIP30可促使肝癌细胞的凋亡,同时上调 Bax、Bad 的蛋白水平而下调 Bcl-xl 的蛋白水平,但对 Bak 蛋白的水平没有影响。结论 TIP30参与的凋亡调节是通过调节 Bcl-2蛋白家族的水平实现的,阐明 TIP30的凋亡信号转导途径可望为肝癌的治疗开辟新的途径。     

Tissue Microarray Immunohistochemical Profiles of p53 and pRB in Hepatocellular Carcinoma and Hepatoblastoma

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation.While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generatedconsiderable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma(HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclearstaining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRbexpression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesispathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveala consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the useof p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty indeciding between HCC and HB.     

The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX) (5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.     

经导管动脉化疗栓塞术在婴幼儿肝母细胞瘤治疗中的应用价值

目的 探讨经导管动脉化疗栓塞术在婴幼儿肝母细胞瘤治疗中的应用价值.方法 将36例婴幼儿肝母细胞瘤患者根据治疗方法 的不同分为对照组(Ⅰ期手术组)18例和观察组(经导管动脉化疗栓塞术联合手术组)18例,然后统计比较2组患者的手术时间、出血量、切除组织重量、围术期的创伤应激指标及手术前后的生活质量评分.结果 观察组的手术时间短于对照组、出血量小于对照组、切除组织重量轻于对照组、创伤应激指标水平低于对照组、生活质量评分好于对照组,差异均有统计学意义(P均<0.05).结论 经导管动脉化疗栓塞术在婴幼儿肝母细胞瘤治疗中的应用价值较好,可为手术治疗奠定良好的基础,且对患儿生存质量的改善也有积极的临床意义.     

Use of Self-expandable Stents for Obstructive Distal and Proximal Large Bowel Cancer: A Retrospective Study in a Single Centre

Aim

The aim of our retrospective study was to determine the effectiveness and safety of self-expandable metal stents in patients presenting with large bowel obstruction secondary to colorectal cancer (regardless of the tumour site), in a district general hospital setting.

Methods

All patients who had endoscopic colonic stents insertion for obstructive colorectal cancer between 2001 and 2005 at our centre were identified retrospectively from patients' discharge database and the unit database. The patients were divided into the 'palliation group' where the stents were inserted to relief symptoms only and the 'bridge group' where patients with resectable cancer underwent colonic stenting as a bridge to improve patient's general condition before definite surgery.

Results

Thirty-eight patients were included in the final analysis. Thirty-three tumours were in the distal colon and five were in more proximal lesions. Stent insertion was successful in 35 patients (92%). Overall clinical success was 71%. All five proximal colonic tumours (13%) had successful stent insertion. Mortality related to procedure was 2%, and the average survival in all patients was 141 days from time of stent insertion.

Conclusion

Colonic stent is a safe and effective method for relief of immediate symptoms of malignant distal and proximal large bowel obstruction.     

Improved Outcomes of Childhood Acute Lymphoblastic Leukemia: A Retrospective Single Center Study in Saudi Arabia

Objective: Understanding the clinical and genetic characteristics of pediatric acute lymphoblastic leukemia (ALL) patients may help assigning the appropriate treatment. This study aims to understand patients’ characteristics, “real-world” treatment practice and outcomes of pediatric ALL. Methods: A cohort of 213 pediatric ALL patients, treated at (King Faisal Specialist Hospital and Research Center –Jeddah branch) KFSH and RC-J during the period of January 2002 to December 2015 were analyzed retrospectively. Statistical analyses were performed on patients’ demographic, clinical and genetics characteristics and outcomes of different treatment protocols. Survival was evaluated using Kaplan-Meier method, and differences in survival were tested using Log-Rank. Significance was set at 0.05 level. Results: Median age of the study cohort was 5 years (range 0.5–15 years) with 55.4% of male population. Majority of the patients had pre-B-cell ALL (88.7%), WBC count <50, 000/μL at diagnosis (76.1%, median = 13.5/μL with a range of 0.51–553.0/ μL) with involvement of central nervous system (CNS) disease in 8.5%patients.Different common chromosomal anomalies or abnormalities, including t(12, 21) translocation, MLL genre arrangements, trisomy (4, 10, 17)and others, were detected. Early response to the risk-directed treatment received by the patients (91.1% achieving <5% blast in the bone marrow) as well as the end of induction outcome (96.2%) was encouraging. Conclusion: We found that the patients’ clinical characteristics and distribution of genetic abnormalities were similar to those of the western countries. Our findings show that the earlier gap between the western countries and KSA in terms of survival has been closed and that competitive outcomes can be achieved with local infrastructure.     

肝癌细胞凋亡中TIP30对Bcl-2蛋白家族的表达的调节

目的TIP30为一新发现的可引起细胞代谢抑制和凋亡的因子。最新研究表明：TIP30可引起Bcl-2家族的两个促凋亡的成员Bad和Bax的表达升高并抑制小鼠肿瘤生长。本实验的目的在于研究在肝癌细胞系HepG2、Hep3B和Hu-7的凋亡中,TIP30所参与的信号转导途径。方法采用MTT、原位DNA末端标记、免疫印迹法研究TIP30引起的细胞凋亡及其对Bcl-2蛋白家族的调节。结果TIP30可促使肝癌细胞的凋亡,同时上调Bax、Bad的蛋白水平而下调Bcl-xl的蛋白水平,但对Bak蛋白的水平没有影响。结论TIP30参与的凋亡调节是通过调节Bcl-2蛋白家族的水平实现的,阐明TIP30的凋亡信号转导途径可望为肝癌的治疗开辟新的途径。     

Multimodal Management of Testicular Mesothelioma - A Retrospective Analysis From a Tertiary Cancer Care Centre

The main modality of management of paratesticular mesothelioma remains orchiectomy while the use of adjuvant chemotherapy has not yet been explored. We aim to analyse the outcome of the multimodal management protocol in testicular mesothelioma We conducted a retrospective analysis of patients registered and treated for testicular mesothelioma between 2009 and 2019 in an oncology tertiary care hospital. Patients presenting with nodal, metastatic disease were treated with adjuvant, palliative chemotherapy respectively and their response to treatment was periodically monitored. Eight patients (3 early, 1 nodal, 4 metastatic) with median age of 58 years was included in the study. Patients who had limited (early, nodal) disease (n = 4) had overall survival ranging from 20 to 140 months while metastatic disease (n = 4) had poor outcomes with overall survival ranging from 2 to 13 months. Surgery remains to be an important modality of therapy that improves the local control and overall outcomes and the quality of life even in patients with metastatic disease at the time of diagnosis. Adjuvant chemotherapy might play a role in effective management of locoregional disease. The performance status, the extent of disease at the time of presentation are the important prognostic factors in deciding the outcome of the disease management.     

Overview of Childhood Cancers at a Regional Cancer Centre in North-East India

Childhood cancers are relatively uncommon in comparison to adult cancers. There is no literature available toshed light on clinic-pathological types and patterns of care for childhood cancers in our population in North-EastIndia. In this analysis we therefore tried to determine the common childhood cancers diagnosed in our institute,clinical profile of the patients, types of treatment and compliance, and median survival estimates. Leukemia wasmost common, followed by retinoblastoma, central nervous system tumours and lymphomas. Ascertaining theclinic-pathological profile of childhood cancers in our population is essential for allocation and management ofresources for this small but important group of patients.     

84例原发性肝癌患者肝动脉化疗栓塞术后预后的影响因素分析

目的 探讨原发性肝癌患者肝动脉化疗栓塞(TACE)术后预后影响因素及预后诊断指标的价值.方法 选取行TACE治疗的84例原发性肝癌患者,采用Cox风险比例模型分析患者的预后因素,另选取80例肝囊肿患者为对照组,采用酶联免疫吸附法测定两组患者的血清AFP、SCC、CYFRA21-1水平.结果 经Cox风险比例模型分析可知,门脉癌栓、肝内转移、Child-Pugh分级、AFP术后阳性、SCC术后阳性、CYFRA21-1术后阳性是原发性肝癌患者远期预后的独立危险因素.原发性肝癌组患者TACE术前、术后血清AFP、SCC、CYFRA21-1水平及AFP、SCC、CYFRA21-1阳性率均高于对照组,而TACE术后血清AFP、SCC、CYFRA21-1水平及AFP、SCC、CYFRA21-1阳性率低于TACE术前,差异均有统计学意义(P<0.05).结论 AFP术后阳性、SCC术后阳性、CYFRA21-1术后阳性是原发性肝癌患者TACE术后预后的独立危险因素,在预测原发性肝癌患者TACE术后预后方面具有潜在的临床价值.     

Chemotherapy-Induced Peripheral Neuropathy in Egyptian Patients: Single Institution Retrospective Analysis

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity that requires treatmentmodification or cessation and worsens patients’ quality of life. Its incidence is 30–40%. Occurrence and severity dependon treatment- and patient-related factors. The symptoms are self-limiting with recovery rate about 50%. Methods:This retrospective analysis took place in our chemotherapy unit. We included patients treated between January 2014and December 2015. Results: 250 patients were eligible. 53 received paclitaxel, 78 received docetaxel, 64 receivedcisplatin and 55 received oxaliplatin. Mean age was 50.11 years. Frequency of CIPN was 46.8% (Grade I 70.9%, GII24.7%, GIII 4.4%). It was 74% with oxaliplatin, 73.5% with paclitaxel, 35.9% with cisplatin and 17.9% with docetaxel.After median of 6 months 24% of patients recovered completely. No significant correlation between occurrence ofCIPN and age (p = 0.781), while was significant with cisplatin (p = 0.043). Diabetic patients had higher incidence (p= 0.007). With cisplatin, median cumulative dose of 450 mg/m2 and ≥ 6 cycles had higher incidence of CIPN (p 0.006and 0.010; respectively). With oxaliplatin, none was correlated with CIPN frequence. With paclitaxel, CIPN was morefrequent if ≥ 4 cycles were received (p = 0.005). With docetaxel, > 4 cycles or cumulative dose ≥ 360 mg/m2 had higheroccurrence of GII CIPN (p < 0.001 for both). Conclusion: CIPN is common problem that affects patients’ quality oflife and leads to treatment interruption. There are many factors affecting its incidence and severity.