Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ABSTRACT
Year : 2014  |  Volume : 10  |  Issue : 6  |  Page : 1-4

Oral Presentations


Date of Web Publication29-Oct-2014

Correspondence Address:
Login to access the Email id

Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions

How to cite this article:
. Oral Presentations. J Can Res Ther 2014;10, Suppl S2:1-4

How to cite this URL:
. Oral Presentations. J Can Res Ther [serial online] 2014 [cited 2019 Nov 14];10:1-4. Available from: http://www.cancerjournal.net/text.asp?2014/10/6/1/143617

Breast

Role of addition of Taxanes to the standard neoadjuvant chemotherapy regimen in the multimodality management of Locally advanced Breast Cancer


Shraddha Raj

Anbarasi Kumaresan Cancer Institute, Adyar, Chennai. E-mail: shraddharaj@ymail.com

Background: The importance of incorporating taxanes in the management of breast cancer has been well established. In our study, we have changed the sequence in order to lessen the overall treatment time and to improve the results. Aims and Objectives: To determine the efficacy and safety profile of Paclitaxel in combination of FAC regimen and compare it with the existing FAC regimen in the multimodality management of Locally Advanced Breast Carcinoma. Materials and Methods: A total of 130 patients of LABC were randomised into 2 arms to receive following treatment- ArmI (c-Arm): Neoadjuvant Chemotherapy with FAC followed by Surgery and Radical Radiotherapy. Arm II (s-arm): Neoadjuvant Chemotherapy with PFAC followed by Surgery and Radical Radiotherapy. All the patients under both the arms received the Chemotherapy for 6 cycles. After completion of chemotherapy, the response (OR, CR, PR) and toxicities were noted. Then, the patients were sent for surgery, and subsequently, Radical Radiotherapy was administered to all patients. The patients were followed up for a maximum of 24 months after treatment, till Aug '10. Results: The s- arm shows 78.5% Overall Response (OR) as compared to 63.1% in the c-arm, with an absolute benefit of 15.4% (P value0.0335). At the end of 24 month follow-up, the cumulative DFS is 72% in the s-arm, and 64% inthe c-arm, showing a benefit of 8%. (P value-0.2253). And, the cumulative OS is 79% in the s-arm, as compared to 66% in the c-arm (P value- 0.0395). There was a statistically significant rise in the Peripheral Neuropathy (P value 0.0001) as well as diarrhoea (P value 0.0001) in the study group. The occurrence of anaemia (P value- 0.054) and leucopenia (P value- 0.014) were also significant. Conclusion: The present work entails that the addition of Paclitaxel to the standard chemotherapy regimen in the neoadjuvant setting, followed by Surgery and Radical Radiotherapy enhanced the Overall Response and Overall Survival significantly.

Gynaecological Malignacy

Investigation on the role of low dose radiation as chemo-potentiator in locally advanced carcinoma cervix: A new treatment paradigm based on radiobiological advantage


Saikat Das

E-mail: drsaikatdas@gmail.com

Background: With standard chemoradiation locally advanced Carcinoma of the uterine cervix (>FIGO stage IIB) often has suboptimal response due to tumor size and hypoxia. Radiobiologically, chemo-potentiating effect of low dose radiation therapy (LDRT) in the range of 40-100 cGy enhances cell killing by cellular arrest in G2 phase (induced radio-resistance or IRR) thus augmenting the effect of G2 cycle specific chemotherapy. Purpose: To examine the response of cervical cancer cell line (HeLa cell line) to low dose radiation using clonogenic assay and mathematical modeling of the low dose response by Joiner's induced repair model. Translational study to evaluate the clinical response of ultra-fractionated low dose radiation and chemotherapy in locally advanced carcinoma cervix. Methods: Survival of HeLa cells following exposure to single and fractionated low doses of Ƴ (gamma)-ray was measured by clonogenic assay. The low dose cellular response was modeled by Joiner's induced repair model (S.F. = e-ar (1+(as/ar -1) e-D/Dc) D-bD2). In the clinical component of the study (Phase II design) patients with squamous cell carcinoma cervix (FIGO stage IIB-IIIB) were included. Patients received two cycles of paclitaxel (175 mg/m2), carboplatin, (AUC × 5), and four concurrent 80-cGy fractions of radiotherapy (two each on Days 1 and 2, and 22 and 23). Clinical and radiological response was assessed after 3 weeks. All patients received standard treatment following neo-adjuvant treatment. Results: HeLa cell line demonstrated marked low dose response consisting of an area of HRS and IRR in the dose region of <1 Gy. The two gradients of the low dose region (as and ar) were distinctly different with a transition dose (Dc) of 0.30 Gy. In the fractionated radiotherapy experiments, for the schedules 0.5 GyX 4, 0.8 GyX 4, 1 GyX 2 and 2 Gy single dose the survival fractions were 0.36 ± 0.05, 0.26 ± 0.06, 0.13 ± 0.05 and 0.05 ± 0.02 respectively. In the Phase II design, total 24 patients (80% IIIB and 20% IIB) were recruited. Mean gross tumor volume (GTV), based on T2 high resolution MRI, before and after neoadjuvant treatment were 54.36 ± 9.75 vs. 11.45 ± 2.39, P < 0.0001 (paired t-test). GTV volumes based on CT and MR were highly correlated (R2 = 0.87). The incidence of grade 3 and 4 neutropenia was 33% and 8% respectively during the entire period of treatment. There was no grade 3 or 4 acute non-hematological toxicity. Conclusion: Neo-adjuvant LDRT and chemotherapy prior to definitive chemoradiation is a novel and feasible approach in cervical cancer with a favorable toxicity profile. This treatment paradigm resulted in significant reduction in the GTV, superior response rate and therefore is a good alternative option for bulky, hypoxic cervical tumors.

Head and Neck

Comparison Between IMRT, 3DCRT and Conventional Radiotherapy Technique in Laryngeal Cancer: A single institution experience.


Deep Shankar Pruthi*, Meenu Gupta*, Vipul Nautiyal*, Saurabh Bansal*, Manisa Pattanayak**, Sunil Saini**, Mushtaq Ahmad*

Department of Radiation oncology*, Surgical Oncology**, Cancer Research Institute, Swami Rama Himalayan University, Dehradun. E-mail: dsp008@gmail.com

Aim: To compare the outcome and toxicity profile of Intensity modulated radiation therapy (IMRT) versus Three-dimensional conformal radiotherapy (3DCRT) versus conventional technique for laryngeal carcinomas-A retrospective analysis. Methods: Retrospective analysis of non-operated biopsy-proven squamous cell carcinoma of Larynx between time period Jan 2010 - Dec 2012 treated with radical EBRT was done. The primary end point was Overall Survival, Local Control and Toxicity Profile. Results: A total of 84 patients were included in study. Out of these 21 treated with IMRT, 33 with 3DCRT and 30 with conventional technique completed the treatment. The mean age was 59.3 years (range 38-78 years, median 60 years) and male: female ratio 15.8:1. The AJCC stage distribution included 11 patients (52.3%) with stage I and II in IMRT, 17 (51.5%) in 3DCRT group and 11 (33.3%) in conventional group. Stage III and IV (M0) included 10 patients (47.6%) in IMRT, 16 (48.4%) in 3DCRT and 19 (63.3%) in conventional group. Most common site was supraglottis (50 patients) followed by glottis (34 patients). Most common histopathology was moderately differentiated (53 patients) followed by poorly differentiated (17 patients), well differentiated and CIS were 7 patients each. Median Dose to CTV for all techniques was 66Gy. Median overall survival was 26.5 months, 24.5 months and 24 months for IMRT, 3DCRT and conventional technique respectively. 2 year LC was 75.7% (IMRT), 70.3% (3DCRT) and 66.6% (conventional) respectively. The 1 year and 2 year OS was 80.9% and 71% for IMRT, 81% and 68% for 3DCRT group and 80% and 63% for conventional technique. Among toxicities, 14.2% (3) developed Grade I mucositis, 28.5% (6) Grade II Mucositis for IMRT, 30.3% (9) developed Grade I mucositis and 39.3% (13) Grade II mucositis in 3DCRT group, 23.3% (7) developed Grade I mucositis and 73.3% (22) grade II mucositis and 1 patient developed grade III mucositis for conventional technique. Grade I and 2 dysphagia was 9.5% (2) and 4.7% (1) for IMRT, 12.1% (4) and 9% (3) for 3DCRT and 60% (18) and 26.6% (8) for conventional technique. Acute Grade II Laryngitis was seen in 23.8% (5) for IMRT and 39.3% (8) in 3DCRT and 46.6% (14) for conventional technique. Grade II skin reaction developed in 9.5%, 72.7% and 85% of patients respectively. Conclusion: No significant difference of OS was found while comparing IMRT vs 3DCRT vs 2D. But results of toxicity profile showed that IMRT is better compared to 3DCRT or 2D technique. However sample size is too small to draw statistically significant conclusions.

Assessment of nutritional status and changes in lean body weight in patients with head and neck cancer undergoing treatment

Kailash Mittal, Nishu Bala, Piyush Kumar, DP Singh, Kranthi Kumar, Bindu

E-mail: drkkmittal@gmail.com

Introduction: The incidence of malnutrition among cancer patients has been estimated at between 40 and 80%. Cancer cachexia has been implicated in the deaths of 30-50% of all cancer patients. Malnutrition is a common problem in patients with head and neck cancer. During treatment (radiotherapy alone or combined with chemotherapy or surgery) malnutrition may develop or aggravate as a result of reduced dietary intake due to treatment-related oral symptoms, such as chewing and swallowing problems, pain, dry mouth, sticky saliva, and taste disturbances and (chemo) radiation-induced mucositis. In malnourished patients, lean mass depletion results in reduced response to cancer treatment, reduced physical activity, reduced quality of life, and prolonged length of hospital stay. Aims and Objective: The purpose of this study was to assess the nutritional status and changes in Lean Body Weight (LBW) in patients with Head and Neck cancer undergoing treatment (Radiotherapy, either alone or combined with Chemotherapy and Surgery). Material and Methods: Forty Seven histo-pathologically proven head and neck cancer patients presenting to the Radiotherapy Department from December 2012 to April 2014 for radical intent radiotherapy with or without chemotherapy, were included in this study. Nutritional status using PG-SGA tool and changes in LBW were assessed. LBW was calculated from Body Fat % which in turn was derived from 4- site skin fold thickness using Durnin and Womersley equation. Patients were assessed in the week before and at completion of treatment. Results: Mean age was 50.68 years. Site wise distribution was as: Oropharynx- 51% (24/47), Hypopharynx- 8.5% (4/47), Nasopharynx- 2% (1/47), Larynx- 13% (6/47) and Oral cavity- 24.5% (12/47). Stage wise (I: II: III: IV) distribution was 3:17:16:11 respectively. According to SGA classification 34% (16/47) patients were well-nourished and Pretreatment prevalence of suspected or moderate and severe malnutrition was 66% (31/47). Scored PG-SGA identified 78.72% (37/47) of patients as requiring active (20/47) or critical (17/47) nutritional intervention. Eighty seven percent patients (41/47) received Chemoradiation (CCRT) and rest had Radiotherapy alone; three patients were candidates for Post-op CCRT. Median Duration of treatment was 8 weeks. After treatment 97.4% (46/47) patients were identified as having need for active or critical nutritional intervention. Mean PG-SGA Score before and after the treatment was 7.28 vs 11.02 (P = 0.0001), respectively, indicating statistically significantly worsening of nutritional status. During treatment, body weight (- 4.32 ± 4.13 kgs; P = 0.0001) and LBW (- 2.03 ± 2.34 kgs; P = 0.00012) significantly declined with LBW representing 47% of total weight loss. There was a trend for higher LBW loss in moderately or severely malnourished patients. Decline in LBW didn't reach statistical significance (P = 0.34) across the SGA classes (A, B and C) indicating global decline in LBW irrespective of pretreatment SGA classification. Conclusion: Patients with Head and Neck Cancer fail to maintain nutrition status during treatment and results in significant decline in body weight and LBW. Chemoradiation in such patients should combine nutrition with activities to support lean tissue anabolism.

Sandwich mould brachytherapy for cancer lip-a non invasive approach

Kanhu Charan Patro, E. B. Rajmohon

E-mail: drkcpatro@gmail.com

Abstract: Carcinoma lip one of the common malignancies among gutkha chewers. Surgery is the mainstay of treatment. Radiotherapy is another option for cosmetic region. External beam radiotherapy can be considered for where surgery is not feasible, medical co morbidity, and when surgery is not acceptable for cosmetic disfigurement. Brachytherapy can be considered for node negative diseases, interstitial brachytherapy is a established procedure. Here we are describing another brachytherapy procedure called sandwich mould as a curative option for node negative disease. A 67 year old male presented with 2 skip lesions on lower lip, one is measuring 3 cm × 3 cm and another is at right angle of mouth 3 cm x 2 cm without any neck node. Patient was not interested for surgery because of cosmetic issues. Options are discussed with patient and patient was agreed for sandwich mould brachytherapy. A mould was made on a orfit frame.around 22 needles are planned in two plane. A CT based plan was done. Patient received @3.5Gy twice dally fraction for 15 fractions BED 2Gy equivalent calculated and discharged with grade 3 RTOG skin and mucosal toxicity. The toxicity increase till 3 weeks of radiation.now there is complete response of tumor. We concluded that sandwich mould brachytherapy is a good option and can be accepted as good option comparing to other options and more suitable for patients having medical co-morbidity and patients are not accepting the cosmetic defects. It is also a good option comparing to interstitial as non invasive.

Advances in Radiation treatment

Stereotactic Body Radiotherapy using Xsightspine tracking system for multiple myeloma in trochanter using cyberknife - A case study


D. Sankara Mahadev, N. Janardhan, P. Bhavani, J. Surendran, N. SyedIbrahim

Omega Hospitals, Hyderabad-500 034, India.

Email: drdoddala@gmail.com

Introduction: A 75 year old female presented with complaints of pain in right leg. Patient was advised to undergo PET scan for diagnosis after preliminary tests. PET scan revealed the presence of metabolically active lytic lesion in the greater trochanter with breaks in the cortex. Another metabolically active mixed lytic and scelerotic lesion in the body of L5 vertebra with demonstrable soft tissue component extending to the left side was also present. Biopsy from right femoral lesion confirmed the condition as plasma cell neoplasm which could be Multiple Myeloma. Patient was put under chemotherapy. Following this, Stereotactic Body Radiotherapy was considered for both L5 and right trochantric lesion due to the lesion size, less critical structures nearby, patients age, an overall shorter treatment time and stay in hospital. Aim and Objective: Though, both the lesion size was indicative for Cyberknife based SBRT, lack of a suitable tracking system for the trochantric lesion posed a challenge. However, a previous study suggested about the effectiveness of XSightSpine tracking algorithm for pelvic bone lesion when the lesion is located not greater than 17 cm radial, while keeping the tracking mesh at the centre of L4-L5 vertebrae. But, in this study, the objective was set to assess the clinical effectiveness of keeping the tracking mesh at the level of the right trochantric lesion due to an acceptable heterogeneity present in the trochanter while ensuring meticulous visual check throughout the delivery. Materials and Methods: Immobilization was made using vacloc and planning CT images were acquired as per hospital protocol. PET assisted CTV delineation was done for SUV values greater the 3.0 for which a 1 mm margin is considered as PTV. Right trochanter PTV volume was about 67 cc. Planning was done using Multiplan version 4.6 with Iris collimator for a prescription dose of 24 Gy in 3 fraction. An isodose line level of 81% is accepted for delivery. The only critical structure near the right trochantric lesion was the right femoral head. The dose to 10cc volume of femoral head is 8.9 Gy. The treatment time for each fraction was about 30 minutes. Treatment was delivered using Cyberknife VSI system. Overall translational and rotational errors for all the three fractions observed were lesser than 2 mm and 30. Results and Discussion: A seven month follow up PET showed an evidence of significant response in right greater trochanter with post treatment SUV value of 0 whereas the pre-treatment PET SUV value was 8.2. Patient is also free pain and with no side effects. In view of this, the effectiveness of XSightSpine tracking algorithm for a non-spine region should be chosen only when an acceptable heterogeneity for spine tracking algorithm is observed and a very meticulous check during the entire course of delivery should also be done.

Breast

Retrospective analysis of efficacy and toxicity of hypofractionated radiotherapy in breast cancer


Rohini Khurana, Ritusha Mishra, Madhup Rastogi, Rahat Hadi,

M. L. B. Bhatt

E-mail: drrohinisethi@gmail.com

Aim: To study the efficacy and toxicity of hypofractionated radiotherapy in breast cancer. Material and Methods: Between October 2012 and September 2014,140 patients of histopathologically proven carcinoma breast were registered in Radiation Oncology OPD in our tertiary care centre. These patients received stage appropriate treatment including radiotherapy for locoregional disease control wherever indicated. However during the course we started hypofractionated radiotherapy as there was enough evidence in literature in its favour. This study tries to analyse the patient characteristics at presentation, risk factors, surgery performed along with status of axillary lymph node dissection and the efficacy as well as toxicity of hypofractionated radiotherapy. Observation: Of the 140 registerd patients it was observed that 58% were postmenopausal and 98%had history of painless lump; 4%were nulliparous, 45% had upper outer quadrant involvement followed by central quadant involved in 23% cases. The data regarding the surgical details show that 20% patients underwent breast conservation surgery and 85% patients had adequate axillary lymph node dissection while 4% cases underwent sentinel lymph node biopsy. Early breast cancer constituted 28% i.e.Stage I and II, 22% were metastatic at the time of presentation while remaining 50% patients belonged to locally advanced group. Most commonly used first line chemotherapeutic agents were anthracycline and taxanes and 4% patients received lapatinib, 8% patients received targeted therapy against Her2/neu. The data regarding radiation therapy reveals that 30% patients received hypofractionated radiotherapy dose given as 4240cGy in 16 fractions; 24% had conventional radiotherapy dose given as 5000cGy/25# while 24% patients did not received radiotherapy. In hypofractionated radiotherapy the skin reactions were Grade I in 80% and Grade II in 20%, dysphagia grade I in 30%lymphedema was seen in 2% of cases, pulmonary toxicity and brachial plexopathy was not seen yet in any of the patients. Medical oophorectomy was done in 2 patients while radiation oophorectomy was done in a patient who had history of liver transplant.During follow up 5% had locoregional recurrence while 6% had distant relapse. Conclusion: Hypofractionated radiotherapy seems to be equally efficacious and no more toxic than conventionally fractionated radiotherapy in carcinoma breast. Further follow up is required to observe the long term toxicity profile.

Genitourinary

A prospective observational feasibility study of hypofractionated radiotherapy in localized carcinoma prostate-Indian Scenario


Vijay Anand Reddy P.

E-mail: vijayanandpreddy@gmail.com

Introduction: Studies have shown prostate cancer to have a low a/b (1.5Gy) when compared to the surrounding normal tissues. Several studies have shown the isoeffectivess of hypofractionation in localised carcinoma prostate. Aims and Objectives: The aim of the present study is to assess the feasibility of using hypofractionated radiotherapy regimen for localized adenocarcinoma prostate, by evaluating the acute and late toxicities, biochemical response and quality of life. Methods: This is an ongoing phase II study where patients with localized adenocarcinoma prostate (low, intermediate and high risk node negative) were treated with radiotherapy on NovalisTx with volumetric modulated arc technique. Twenty patients accrued between November 2011 and November 2013 were analysed preliminarily. The regimen followed was 67.5Gy in 25 fractions at 2.7Gy per fraction to the prostate and 50Gy in 25 fractions to the lymphnodes in high risk patients. All intermediate and high risk patients used hormonal therapy. Toxicities (RTOG toxicity criteria) and quality of life scores (EORTC QlQc-30 and PR-25) were assessed every week during radiotherapy and at 3,6, 9 and 12 months after radiotherapy. Results: Twenty patients were analyzed, of which 4/20 (20%) were low risk, 3/20 (15%) intermediate and 13/20 (65%) high risk. Median age was 68.5yrs (60-80 yrs). Median P.S.A. at presentation was 19.43 ng/ml. Median follow up period is 12 months. Acute gastrointestinal toxicities were maximum at 5 th week during RT while the acute genitourinary toxicities were maximum at 4 th week during RT. Most of the patients (55%) had grade 1-2 toxicities. On evaluation of late toxicities, it was seen that the genitourinary toxicities were maximum at 6 months while the gastrointestinal toxicities were maximum at 9months post RT. QOL analysis revealed improvement in global health score, role, emotional, social and physical functioning scores at 12 months when compared to pretreatment. Urinary and bowel symptoms score reached peak at the end of treatment and declined at 3 months post RT compared to the baseline. Urinary and bowel symptoms score had a peak again at 9 months post RT. Median P.S.A. at the end of 12 months post RT was 0.013ng/ml. None of the patients had late grade 3 and above gastrointestinal and genitourinary toxicities. None of the patients had a biochemical relapse during the follow up period. None of the patients had treatment interruptions due to toxicities. Conclusion: This study shows that hypofractionation in localised adenocarcinoma prostate is feasible and is associated with acceptable acute and late toxicities and improvement in quality of life.

Head and Neck

Hyponatremia: Is there an association with disease profile in head and neck malignancies? Audit from a tertiary cancer care centre


Chelakkot G. Prameela, Rahul Ravind, P Md. Zaheeruddin

Clinical Associate Professor, & Consultant, Department of Radiation Oncology, Amrita Institute of Medical Sciences. Kochi. Kerala. 682041

E-mail: cgprameela@gmail.com

Background: Incidences of 3%-30% of hyponatremia in hospital population in general, and up to 58.1% in cancer patients, have been quoted by Kumar
et al. from MD Anderson [1] . Prognostic value of low serum sodium concentration for mortality has been well described for myocardial infarction, congestive heart failure and also for cancer [2] . Increased incidence of hyponatremia was noticed among our patients with head and neck malignancies on external beam radiation. Hence we retrospectively analysed incidence and patterns of hyponatremia and also the factors that might influence hyponatremia, in patients with head and neck malignancies, as an institutional audit. Materials and Methods: Patients with head and neck cancers treated with radical intent from January, 2011 to December, 2012 were analysed. Data from electronic medical records were retrieved. Hyponatremia was graded according to CTCAE version 3.0, as Grade 0, if >135 mEql/L, Grade I, if between 130 mEq/L to 135 mEq/L, Grade II, if between 120 and 130, and Grade III, if <120 mEql/L. Patients were grouped based on their sodium status while on treatment, into group I (hyponatremic) and group II (eunatremic). Each of these groups was sub-grouped as A and B based on treatment interruptions. The individual variables looked into were sex, age, stage of disease; surgical status, concurrent chemotherapy status, and initial sodium status, and univariate and multivariate analysis of these were done. Results: Study-group included 271 patients. 68.3% had developed hyponatremia. Group IA [70 patients] had hyponatremia and interruptions to treatment, and comprised of patients > 50, advanced stage needing chemoradiation, and also had initial hyponatremia. Group IIB the other extreme of the spectrum included young patients, with early stage not requiring concurrent chemotherapy, were eunatremic initially and had uninterrupted treatment. Age (>50-years) was a significant factor in the development of hyponatremia, in multivariate analysis (P-0.018). Advanced stage was associated with increased incidence of hyponatremia (P-<0.001). Surgery prior to radiation, (univariate - P-0.009; multivariate - P-0.005), and concurrent chemotherapy (univariate - P-<0.001; multivariate - P-<0.001) significantly increased the risk of developing hyponatremia. Hyponatremia prior to initiating radiation also carried significant risk of developing hyponatremia on radiation (univariate - P-<0.001; multivariate - P-<0.001). Incidence of interruptions to radiation treatment was higher in patients having hyponatremia (P-0.002). Conclusion: One fourth population of head and neck malignancies belong to elderly [3] . Factors predictive of improved survival on univariate analysis suggested by Suntharalingam et al. [4] are, age <50 years, concurrent chemotherapy using carboplatin and/or paclitaxel and treatment breaks of less than five days. Our analysis indicates an increased sodium imbalance in head and neck malignances. Age, stage of disease, surgery, chemotherapy, and hyponatremia prior to start of treatment, were found to be significant, independent risk factors for developing hyponatremia. Hyponatremia is a biochemical diagnosis that is easily detected clinically and is correctable with cost-effective out-patient care. Further information on this would help to have a clearer perspective in the management of these patients and to improve outcomes and quality of life.




 

Top
 
 
  Search
 
Similar in PUBMED
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article

 Article Access Statistics
    Viewed654    
    Printed39    
    Emailed0    
    PDF Downloaded117    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]