Karachi Institute of Radiotherapy and Nuclear Medicine

Karachi, Pakistan

Karachi Institute of Radiotherapy and Nuclear Medicine

Karachi, Pakistan

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Afsar N.A.,Alfaisal University | Afsar N.A.,Ziauddin University | Ufer M.,University of Kiel | Ufer M.,Novartis | And 8 more authors.
European Journal of Clinical Pharmacology | Year: 2012

Purpose The cytotoxic drug cyclophosphamide (CP) is bioactivated into 4-hydroxy-cyclophosphamide (4-OH-CP) through cytochrome P450 enzymes and cleared through aldehyde dehydrogenase and glutathione S-transferase. This prospective study analyzes the influence of drug metabolizing enzyme genotype on (1) plasma 4-OH-CP:CP ratio and (2) myelotoxicity in breast cancer patients on 500 mg/m 2 cyclophosphamide. Methods Sixty-eight female breast cancer patients on FAC (fluorouracil, adriamycin, cyclophosphamide) were included. Genotyping of cytochrome P450 enzymes CYP2B6, CYP2C9, CYP2C19, CYP3A5, aldehyde dehydrogenase (ALDH3A1), and glutathione S-transferase (GSTA1) was done either through RFLP or pyrosequencing. Plasma CP and 4-OH-CP were measured immediately and 1 and 2 h after the end of infusion through LCMS. The leukocyte count was determined on day 10 and 20 after chemotherapy. Results At CP dose of 500 mg/m2, the 4-OH-CP:CP ratio was negatively affected by CYP2C19*2 genotype (p=0.039) showing a gene-dose effect. Moreover ALDH3A1*2 genotype increased 4-OH-CP:CP ratio (p=0.037). These effects did not remain significant in a univariate analysis of variance including all genotypes. GSTA1*B carriers were at increased risk of severe leucopenia (OR 6.94; 95% CI 1.75-27.6, p=0.006). Conclusion The myelotoxicity in patients receiving FAC is related to the activity of the phase-II enzyme GSTA1 but is independent of the formation of 4-OH-CP. © Springer-Verlag 2011.


Bano N.,Ziauddin University | Najam R.,University of Karachi | Qazi F.,Jinnah University for Women | Mateen A.,Karachi Institute of Radiotherapy and Nuclear Medicine
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX. Materials and Methods: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared. Results: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin 130 mg/m2). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin 85mg/m2). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin 100mg/m2). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05). Conclusions: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm.


Afsar N.A.,Ziauddin University | Haenisch S.,University of Kiel | Mateen A.,Karachi Institute of Radiotherapy and Nuclear Medicine | Usman A.,Jinnah Postgraduate Medical Center | And 4 more authors.
Basic and Clinical Pharmacology and Toxicology | Year: 2010

Polymorphic genes of drug metabolizing enzymes and transporters may influence drug response. With some exemptions, single nucleotide polymorphisms in such genes, however, are not known to be susceptibility factors for breast cancer. This study explored genotype profiles for the breast cancer patients on fluorouracil, doxorubicin and cyclophosphamide (FAC) in a Pakistani set of population and their comparison with HapMap data. Sixty-eight female breast cancer patients were included. All received FAC chemotherapy. Relevant genotyping was done either through restriction fragment length polymorphism or pyrosequencing. The variant allele frequencies were: 5.1% for CYP2C9 *2 (430C>T), 15.4% for CYP2C9*3 (1075A>C), 27.2% for CYP2C19*2 (681G>A), 33.1% for GSTA1*B (-69C>T, -52G>A), 62.5% for ALDH3A1 *2 (985C>G), 58.8% and 4.4% for ABCB1 (2677 G>T/A), 64.7% for ABCB1 3435 C>T, and 15.4%, 33.1% and 39.7% for ABCC2 (-24 C>T, 1249 G>A and 3972 C>T). In comparison with HapMap, this first exploration in Pakistani samples shows higher frequency of (i) CYP2C9*3 carriers (p < 0.05) than in Hispanic, Chinese, Japanese and African samples, (ii) ALDH3A1*2 carriers (p < 0.01) than Caucasian, Hispanic, Chinese, Japanese and African samples. For ABC transporters, a higher frequency of variant allele was observed in (iii) ABCB1 2677 G>T/A (p < 0.01) than Caucasian, Hispanic and African, (iv) ABCB1 3435 C>T (p < 0.05) than Chinese, Japanese and African, (v) ABCC2 1249 G>A (p < 0.01) than Hispanic, Chinese and Japanese samples. In conclusion, cyclophosphamide activation and detoxification of reactive intermediates may be altered in the Pakistani. Though carriers of CYP2C19*2 were higher than in Caucasian and Hispanics, they did not reach statistical significance (p = 0.05). © 2010 Nordic Pharmacological Society.


Masroor I.,Aga Khan University | Azeemuddin M.,Aga Khan University | Sakhawat S.,Aga Khan University | Beg M.,Aga Khan University | And 4 more authors.
Cancer Management and Research | Year: 2012

Background: The purpose of this study was to evaluate mammography reports for diagnosed breast cancer cases in major government and private centers in Karachi, Pakistan, with respect to concordance with the Breast Imaging Reports And Data System (BI-RADS®) lexicon. Methods: A prospective, descriptive, multicenter study was conducted in the radiology sections of the Aga Khan University Hospital, Pakistan Naval Station Shifa Hospital, Advanced Radiology Clinic, Karachi Institute of Radiotherapy and Nuclear Medicine, and Civil Hospital Karachi between May and October 2010 after approval from the ethical review committee of Aga Khan University. Mammograms reported as BI-RADS category 4 and 5 were included in the study. Mammograms reported as BI-RADS category 0, 1, 2 and 3 were excluded. Fifty reports were collected from each center. Data were collected about the clinical indication, breast density, location and description of the lesion, calcification, and comments on axillary lymph nodes. This description was compared with the BI-RADS lexicon. Results: The mean age of the patients was 50 ± 12 years. The clinical indication, breast parenchymal density, lesion location, and presence of calcification were better described by the private centers, while description of lymph node status was better stated by the government centers. This difference was statistically significant, except for lesion description. The description of masses by the two reporting groups was comparable. Conclusion: Mammographic reporting of malignant breast lesions in the private sector is more in line with the BI-RADS lexicon, as compared with government sector hospitals in Karachi, Pakistan. Lymph node documentation was better in government sector reports. © 2012 Masroor et al, publisher and licensee Dove Medical Press Ltd.


Ateeq I.S.,Sir Syed University of Engineering and Technology | Muzammil Khan K.,Sir Syed University of Engineering and Technology | Khalid J.,Sir Syed University of Engineering and Technology | Ali M.,Karachi Institute of Radiotherapy and Nuclear Medicine
IFMBE Proceedings | Year: 2013

Electrocardiogram measurement plays a fundamental role for the finding and monitoring of a variety of cardiac problems. In this investigational study we considered three lead computer interface ECG module with PIC Controller, based on the Einthoven's triangle technique. Our developed ECG module operates on bipolar limb lead arrangement and a particular gold plated switch is used for leads selection with the intention to reduce contact noises. LAB WINDOWS software is used to display a real time ECG signal that supports us to evaluate heart rate and PQRST amplitudes. Our investigational outcome illustrates 80% - 90 % precision as compared to conventional ECG machine, therefore it allowing an efficient ECG measurement regardless of artifacts. © 2013 IFMBE.


Zaman M.U.,Aga Khan University | Fatima N.,Karachi Institute of Radiotherapy and Nuclear Medicine | Sajjad Z.,Aga Khan University | Hashmi I.,General Electric | Khan K.,Aga Khan University
Annals of Nuclear Medicine | Year: 2012

Objective Pelvic lymph node dissection (PLND) is the gold standard procedure for nodal staging in prostate cancer (PC) but less commonly used due to its invasiveness. More commonly computerized tomography (CT) and magnetic resonance imaging (MRI) are used although these have limited sensitivities and specificities. The aim of this study was to find out the correlation between higher scrotal uptake ratio (SUR) of 99mTc-methylene diphosphonate (MDP) on bone scan and pelvic node metastasis in patients with PC at high risk for nodal metastasis. Methods This was a retrospective study which included 68 biopsy proven newly diagnosed PC patients who had bone scan from January 2008 till January 2012. MRI of the pelvis, prostate specific antigen (PSA) and Gleason's score were available in all patients. Whole body bone scan was performed in all patients and SUR was calculated by dividing mean counts over scrotum and soft tissue over lateral aspect of right thigh. PLND was carried out within 2-3 weeks of MRI study in these patients. Results Mean age of studied males was 71 ± 07 years with a mean PSA level of 65 ± 162 ng/ml. Prostate biopsy revealed adenocarcinoma in all patients with mean Gleason's score 7 ± 1. Mean SUR was 2.786 ± 0.496. MRI was positive for pelvic lymphadenopathy in 32/68 (47 %).PLND revealed evidence of nodal metastasis in 16/68 (24 %) patients. Receiver operating characteristic analysis revealed good diagnostic strength of SUR for nodal metastasis with a cut off value of >2.99 with an area under curve (AUC) 0.708 (95 %CI 0.533-0.847, p value<0.05) and a mean sensitivity of 68.75 % and mean specificity of 80 %. Diagnostic strength of MRI for nodal metastasis was found to be low (AUC 0.566, 95 %CI 0.047-0.657, non-significant p value). No significant correlation was found between SUR and PSA in nodes positive and nodes negative patients. Conclusion We conclude that in newly diagnosed PC patients, higher SUR on bone scan has a high diagnostic accuracy for pelvic node metastasis. Furthermore, a bone scan with a SUR <2.99 and negative for bone metastasis can stratify newly diagnosed PC patients as low risk. © The Japanese Society of Nuclear Medicine 2012.


Fatima N.,Karachi Institute of Radiotherapy and Nuclear Medicine | Zaman M.U.,Karachi Institute of Radiotherapy and Nuclear Medicine | Hashmi A.,Karachi Institute of Radiotherapy and Nuclear Medicine | Kamal S.,Karachi Institute of Radiotherapy and Nuclear Medicine | Hameed A.,Karachi Institute of Radiotherapy and Nuclear Medicine
Nuclear Medicine Communications | Year: 2011

BACKGROUND: Adriamycin cardiotoxicity begins with the first dose of therapy. The insult may be subclinical initially, but with continued treatment can result in clinical congestive heart failure. Therefore, a study for the detection of early cardiotoxicity of adriamycin by left ventricular ejection fraction (LVEF) estimation using technetium (Tc)-99m multiple-gated acquisition (MUGA) scan and echocardiography (ECHO) was conducted. METHODS: LVEF was assessed in 42 patients with different cancers, advised to receive adriamycin (average received dose=95.2±6.82 mg/cycle, protocol dose=65±10 mg/m) in each of six cycles. The percentage of LVEF (%LVEF) was determined as a baseline after every successive cycle, simultaneously, by a Tc-99m MUGA scan (reference method) and ECHO. RESULTS: A significant decline of 12.17±5.01 and 9.26±4.82 (P<0.001) in %LVEF was noted at the end of adriamycin therapy, estimated by a Tc-99m MUGA scan and ECHO respectively. Thirteen of 42 (31%) and six of 42 (14%) patients developed protocol-defined cardiotoxicity, determined by a Tc-99m MUGA scan and ECHO, respectively. The incidence of cardiotoxicity was 2.4, 2.4, 4.8, 16, and 31.2% at the median cumulative adriamycin dose of 210, 380, 450, 550, and 615 mg/m2, respectively. CONCLUSION: Subclinical adriamycin cardiotoxicity was detectable from the third cycle and if not detected earlier continued therapy may progress to severe and irreversible cardiotoxicity. A decline of 5% or more of %LVEF instead of 10% should be considered as a significant marker of subclinical cardiotoxicity. A Tc-99m MUGA scan is more sensitive than ECHO for the estimation of subtle changes in %LVEF. Ideally, %LVEF must be determined at baseline and after every cycle, and if not possible then preferably from the third cycle onwards. © 2011 Wolters Kluwer Health | Lippincott Williams &Wilkins.


PubMed | Karachi Institute of Radiotherapy and Nuclear Medicine
Type: Journal Article | Journal: Nuclear medicine communications | Year: 2011

Adriamycin cardiotoxicity begins with the first dose of therapy. The insult may be subclinical initially, but with continued treatment can result in clinical congestive heart failure. Therefore, a study for the detection of early cardiotoxicity of adriamycin by left ventricular ejection fraction (LVEF) estimation using technetium (Tc)-99m multiple-gated acquisition (MUGA) scan and echocardiography (ECHO) was conducted.LVEF was assessed in 42 patients with different cancers, advised to receive adriamycin (average received dose = 95.2 6.82 mg/cycle, protocol dose = 65 10 mg/m) in each of six cycles. The percentage of LVEF (%LVEF) was determined as a baseline after every successive cycle, simultaneously, by a Tc-99m MUGA scan (reference method) and ECHO.A significant decline of 12.17 5.01 and 9.26 4.82 (P < 0.001) in %LVEF was noted at the end of adriamycin therapy, estimated by a Tc-99m MUGA scan and ECHO respectively. Thirteen of 42 (31%) and six of 42 (14%) patients developed protocol-defined cardiotoxicity, determined by a Tc-99m MUGA scan and ECHO, respectively. The incidence of cardiotoxicity was 2.4, 2.4, 4.8, 16, and 31.2% at the median cumulative adriamycin dose of 210, 380, 450 , 550 , and 615 mg/m, respectively.Subclinical adriamycin cardiotoxicity was detectable from the third cycle and if not detected earlier continued therapy may progress to severe and irreversible cardiotoxicity. A decline of 5% or more of %LVEF instead of 10% should be considered as a significant marker of subclinical cardiotoxicity. A Tc-99m MUGA scan is more sensitive than ECHO for the estimation of subtle changes in %LVEF. Ideally, %LVEF must be determined at baseline and after every cycle, and if not possible then preferably from the third cycle onwards.


PubMed | Karachi Institute of Radiotherapy and Nuclear Medicine
Type: Journal Article | Journal: Annals of nuclear medicine | Year: 2011

The diagnosis of PE in pregnancy poses a challenge due to pregnancy-related physiological changes. Missing the PE or wrongly treating a pregnant woman for PE has serious clinical consequences. There has been concern over the use of radiation-based imaging modalities due to risk of teratogenicity and oncogenicity. This review is focused on various diagnostic options and risks of radiation to the fetus and mother from radiation-based procedures.


PubMed | Karachi Institute of Radiotherapy and Nuclear Medicine
Type: Journal Article | Journal: Asian Pacific journal of cancer prevention : APJCP | Year: 2011

A changing paradigm shift with multiparity (MP) and breast feeding (BF) has been reported in recent years in breast cancer (BC). Our aim was to observe associations of parity, BF and other risk factors with BC among a local population attending a breast care clinic.A total of 1,039 women (mean age 39 15 years) attended for screening or presented with palpable breast lumps at KIRAN, Pakistan. The majority were in middle and low socioeconomic strata. As per American Cancer Society (ACS) guidelines 2003, mammography and ultrasound were performed, along with fine needle aspiration cytology (FNAC) in 195 women with Breast Imaging Reporting and Data Set (BIRADS) IV/V, high risk patients with BIRADS III on mammography and with suspicious ultrasound findings.The study population was stratified into two groups; one with BC on FNAC in 181 women (17%) and other including 858 healthy women after screening for cancer. The BC group had relative predominance of MP (86% p<0.001), BF (85% p<0.001), family history FH (8% p=0.106) and post-menopause PM (49% p<0.001) as compared to the healthy population. Estimated relative risk (RR) of BC in women with MP, BF, F/H and PM was 3.12 (95% CI=2.05-4.73; p<0.001), 2.47 (95%CI=1.69-3.61; p<0.001), 1.45 (95%CI=0.93-2.41; p=1.06) and 2.33 (95%CI=1.70-3.02; p<0.001) respectively. Higher incidence of BC was observed between 30-40 years 23% (p<0.001) and between 40-50 years 38% (p<0.001).MP, BF and PM have significant associations with BC in the studied Pakistani women and this possible paradigm shift now needs to be evaluated for confounding factors.

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