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Introduction Almonertinib (HS-10296) is a novel, third-generation EGFR tyrosine kinase inhibitor (EGFR TKI) that targets both EGFR-sensitizing and T790M resistance mutations. This first-in-human trial aimed to evaluate the safety, efficacy, and pharmacokinetics of almonertinib in patients with locally advanced or metastatic EGFR mutation-positive NSCLC that had progressed after pevious EGFR TKI therapy. Methods This phase 1, open-label, multicenter clinical trial (NCT0298110) included dose-escalation (55, 110, 220, and 260 mg) and dose-expansion cohorts (55, 110, and 220 mg) with once daily oral administration of almonertinib. In each expansion cohort, tumor biopsies were obtained for the determination of EGFR T790M status. The safety, tolerability, antitumor activity, and pharmacokinetics of almonertinib were evaluated. Results A total of 120 patients (26 patients in the dose-escalation cohort and 94 patients in the dose-expansion cohort) were enrolled. The maximum tolerated dose was not defined in the dose-escalation phase; the 260 mg regimen was not further evaluated in the dose-expansion phase owing to safety concerns and saturation of exposure. The most common treatment-related grade greater than or equal to 3 adverse events were increased blood creatine phosphokinase (10%) and increased alanine aminotransferase (3%). Among 94 patients with the EGFR T790M mutation in the dose-expansion cohort, the investigator-assessed objective response rate and disease control rate were 52% (95% confidence interval [CI]: 42–63) and 92% (95% CI: 84–96), respectively. Median progression-free survival was 11.0 months (95% CI: 9.5–not reached) months. Conclusions Almonertinib is safe, tolerable and effective for patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation who were pretreated with EGFR TKIs.

Introduction: Multinational Association of Supportive Care of Cancer (MASCC) index score is a clinical tool to predict outcomes in Febrile Neutropenia patients. This risk-index score has been authenticated in international trials however local data is deficient. We aimed to determine hospital based incidence rate of serious complications in admitted chemotherapy induced febrile neutropenia patients presenting to a tertiary care hospital. We also aimed to compare proportions of serious medical complications in patients having MASCC score 60 (p = 0.039), MASCC score < 15 (p = 0.002) and an albumin < 2.5 mg/dl (p = 0.046) was associated with higher chance of developing serious complications. Sensitivity, specificity, positive and negative predictive value of MASCC score in predicting risk of serious complications was 21.33%, 100%, 100% and 18.06% respectively. Conclusion: MASCC risk-index score is a useful tool to identify patients at low risk of complications. Hospital based incidence rate of serious complications was 18.2%.

Background: HS-10296 is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is effective against both EGFR-sensitizing and T790M-resistant mutations. This first-in-human trial aimed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of HS-10296 in EGFR inhibitor-resistant non-small-cell lung cancer (NSCLC) patients. Methods: This open-label phase 1 trial included dose-escalation and dose-expansion phases. Patients >18 years with locally advanced/metastatic EGFR mutant NSCLC that progressed after 1st/2nd EGFR-TKI were eligible. Confirmation of EGFR T790M-positive mutation was required for the dose-expansion cohort. During dose escalation, HS-10296 was administered orally at 55 to 260 mg once-daily following a rolling six design. During dose-expansion, patients (30 patients/dose level) received the recommended dose once-daily in 21-day cycles. The primary endpoint was safety and tolerability. Pharmacokinetics and anti-tumor activity of HS-10296 were also assessed. Findings: Between May 2017 and September 2018, a total of 120 patients were enrolled: 26 patients in the dose-escalation cohort and 94 in the expansion cohort. No dose-limiting toxicity occurred in the dose-escalation phase, but no dose expansion was opened for 260-mg because of plateauing of drug exposures. The most common drug-related AEs were increased blood creatine phosphokinase (20%), diarrhea (16.7%), cough (16.7%), and rash (15.8%). The most common drug-related grade ≥3 adverse events were increased blood creatine phosphokinase (10.0%) and increased alanine aminotransferase (3.3%). When considering all patients, no patient had a complete response, 60 (50.0%) had partial response, and 47 (39.2%) had stable disease. The objective response rate and disease control rate were 50.0% (95%CI: 40.7%-59.3%) and 89.2% (95%CI: 82.2%-94.1%) respectively. Median progression-free survival was 9.6 (95%CI: 8.3-11.1) months. Interpretation: HS-10296 is safe, tolerable, and effective in patients with T790M-positive EGFR mutant, locally advanced/metastatic NSCLC who progressed after EGFR-TKI. Trial Registration: This trial is registered with ClinicalTrials.gov, NCT02981108. Funding Statement: This study was funded by the Hansoh Pharmaceutical Group Co. Ltd. Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: The study was conducted according to the principles of the Declaration of Helsinki and the guidelines of the Good Clinical Practice of the International Council for Harmonisation (ICH). The study protocol was approved by the ethics committees of each participating center. Written informed consent was obtained from all subjects before enrollment.

Background: Breast cancer is the most common cancer in Pakistani women. We report the presenting features, treatment patterns and survival of breast cancer from a University Hospital in Southern Pakistan and compare the data with international population based studies. Materials and Methods: Medical records of patients diagnosed to have breast cancer between January 1999 and November 2008 were reviewed retrospectively. Results: A total of 845 patients were identified. Median age of diagnosis was 48 years (range 18-92). Clinical stage was as follows: Stage I 9.9%; Stage II 48.5%; Stage III 26.2%; Stage IV 13.8%; data not available 1.5%. Approximately, half (51.6%) were estrogen receptor (ER) positive and 17.5% over-expressed Her2/neu. Nearly 23% patients received neo-adjuvant chemotherapy while 68.9% received adjuvant chemotherapy. Anthracycline based treatment was the most common treatment until 2003 while later on, patients also received taxanes and trastuzumab based therapy. Age, stage, tumor size, lymph node status, tumor grade, ER status, treatment with hormonal therapy and radiation were the major predictive factors for overall survival (OS). We report an impressive 5 year OS of 75%, stage specific survival was 100%, 88% and 58% for Stages I, II and III respectively. Conclusion: The majority of patients present at a younger age and with locally advanced disease. However, short term follow-up reveals that the outcomes are comparable with the published literature from developed countries. Long-term follow-up and inclusion of data from population-based registries are required for accurate comparison.

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

BACKGROUND: Febrile neutropenia (FN) and myelosupression remain a challenging oncologic medical emergency and dose limiting toxicity associated with chemotherapy for cancers. Various factors are known to affect the outcomes for patients diagnosed with FN. Electrolyte abnormalities have commonly been observed, but the real incidence and their impact has been only scarcely studied in literature. METHODS: This was a prospective, observational study. A total of two hundred and fifteen (215) patients admitted between January 2007 and August 2008 were included. Analysis of data was made using SPSS version16.0.Toxicity profile was graded according to CTC version 3.0. RESULTS: Almost equal number of FN was observed in both solid tumors and hematological cancers with almost equal gender distribution. Of all 83.5% patients demonstrated some electrolyte abnormalities. All grades combined, hypokalemia was seen in 48% of patients, with 51.4% having grade I, 33.3% grade III and 15.2% G IV (life threatening) hypokalemia. Hyponatremia of all grades was seen in 67.9% patients, of them 60.3% had Grade I, 33.3% grade III and 0.7% patients had grade IV hyponatremia. Hypomagnesaemia (70 patients assessed) was seen in 54.3% patient, 94.7% having grade I decline. Average length of stay for patients who received IV electrolyte replacement was 6.3 days compared to 4.9 days in those who did not. Out of 90 patients who required special care unit 75 had electrolyte abnormalities, of 15 patients who expired 13 had electrolyte abnormalities CONCLUSION: This analysis, which is first of its kind, suggests that decline in electrolyte levels is frequently observed in patients presenting with FN. These abnormalities can have independent negative impact on the outcome for such patients. Special attention should be paid to electrolyte imbalance right from the outset.

Stem cell transplantation is curative in a number of otherwise fatal hematological diseases. In Pakistan, SCT was started in October 1995 at Dr Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over 350 allogeneic stem cell transplants have been carried out in these latter two centers. Another 50 autologous procedures were carried out in all centers. In 2004, a third center started transplants at the Aga Khan Hospital. The main indications for transplant are aplastic anemia, beta-thalassemia major and hematological malignancies. HLA-identical sibling donors provide stem cells for the recipient. In 70% of cases, a matched donor is identified. In sharp contrast to the rest of the world, the majority of transplants are allogeneic, donor-recipient pairs are CMV positive and fungal infection, tuberculosis and malaria are particular problems. The early results are promising, with transplant-related mortality reported to be 10-20%, whereas long-term survival is reported to be 78, 72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively. Financial constraints, poor socioeconomic status, poor transfusion services, trained human resources and difficulty in keeping pace with technological advances are major hurdles in the growth of transplant medicine. Government support is badly needed to strengthen existing facilities and to develop more centers.

Cytogenetic abnormalities have long been recognized as the genetic basis of the occurrence of various malignancies. Specific cytogenetic abnormalities have shown to occur recurrently in particular subtypes of leukaemias and lymphomas. t(1;14) is an infrequently occurring recurrent chromosomal translocation that has been described in literature to be associated with haematological malignancies. Trisomy 4 is another rare genetic abnormality which has been reported in association with both acute myeloid and lymphoid leukaemias. The concomitant occurrence of a myeloid malignancy in association with a lymphoproliferative disorder is a distinctly unusual phenomenon. We report the case of a young patient with concomitant T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia with a novel cytogenetic abnormality i.e. t(1;14) with trisomy 4. We believe this is the first reported case where a patient with two concomitant haematological malignancies, harboured this karyotype.

To evaluate the experience of bendamustine in the treatment of B-cell malignancies at a tertiary care centre.The retrospective descriptive analysis included data of all adult patients with B-cell malignancies treated with bendamustine from 2009 to 2011 at the Aga Khan University Hospital, Karachi. Data was analysed using SPSS 17.0. Frequencies and percentages were computed for baseline characteristics, responses and toxicities.Of the 19 patients 15 (79%) were males and 4 (21%) were females.The mean age was 59.53+/-12.14 (with a range of 46-86). Eight (42%) had follicular lymphoma, 6 (32%) had mantle cell lymphoma, 2 (11%) had diffuse large B-cell lymphoma, and 3 (16%) had chronic lymphocytic leukaemia. Four (21%) patients experienced grades 3 and 4 cutaneous toxicities. Eight (42%) patients were treated with bendamustine as first-line therapy. Six of them (75%) were included for response evaluation; 3 (50%) had complete response, and 3 (50%) had partial response. Eleven (58%) patients had relapsed disease out of which 3 (27.27%) had complete response, and 7 (63.63%) had partial response, whereas 1 (9%) had disease progression.Bendamustine given as monotherapy or in combination is safe and useful in the treatment of patients with B-cell malignancies.

Objective. The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan. Materials and Methods. Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 μg twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15 mg/m2 on day +1 followed by 10 mg/m2 on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification. Results. A total of 153 transplants were done from April 2004 to December 2011. Out of these were allogeneic transplants. There were females and males. The overall frequency of any degree of graft versus host disease was 34%. Acute GvHD was present in patients while had chronic GvHD. Grade II GvHD was present in patients while grade III and IV GvHD was seen in patients each. Acute myeloid leukemia and chronic myeloid leukemia were most commonly associated with GvHD. The mortality in acute and chronic GvHD was 8.8% and 12% respectively. Conclusion. The frequency of graft versus host disease in this study was 34% which is lower compared to international literature. The decreased incidence can be attributed to reduced diversity of histocompatibility antigens in our population.

Unplanned excision of soft tissue sarcomas (STSs) outside comprehensive tumor management centers necessitates the need for wide reexcision to achieve adequate margins. We retrospectively reviewed medical records of 135 patients with STS operated at our hospital with the goal of examining outcomes, in terms of local recurrence (LR) and metastasis rate (MR), of reexcision following unplanned excision of STS and comparing results with those of first-time planned surgery. Eighty-four patients had their first-time surgery and 51 patients had come to us following unplanned excision at prereferral hospital. Mean age of all patients was 41.8 ± 21.9 years. The LR and MR was 14.3% and 8.3%, respectively, in patients undergoing first resection, whereas it was 21.4% and 13.7%, respectively, in patients undergoing revision surgery. Average duration from previous unplanned excision was 8 months. Twelve patients were referred immediately after excised specimen revealed STS, while 39 patients presented after evident local recurrence. Wide reexcision was attempted in 48 patients while three patients need amputation. Adjuvant radiotherapy was administered in all patients undergoing limb-sparing surgery. Ten patients needed adjuvant chemotherapy. We conclude that wide reexcision of STS has poorer outcomes compared to planned excision. Therefore, patients with soft tissue masses should be managed by multidisciplinary oncology team at specialized cancer centers.

To explore the effects of cancer on psychosocial aspects of Pakistani patients and their families, assessing the need for interventions to improve their quality of life.A prospective, Cross-sectional study was performed on 200 patients visiting the oncology outpatient facility of AKUH from December 2010 to May 2011 through an interview. Responses were recorded on pre-designed questionnaires including FACT-G QOL (Functional Assessment of Cancer Therapy-General Quality Of Life) component.Out of the 200 patients 52 (26%) were males and 148 (74%) were females. Mean age was 51.8 +/- 14.2 years. Breast cancer accounted for the commonest cancer in females 116 (58%) and lung in males 30 (15%), 100 (50%) patients were currently undergoing chemotherapy. In all 148 (74%) patients were well aware of their diagnosis and were able to cope better and 142 (71%) were well supported by families (majority being financially stable). Major financial impact was found in 42 (21%) cases. Religious/spiritual help was sought by 138 (69%) patients predominantly females- 113 (76%) and 22 (11%) patients consulted a psychiatrist; 20 (94%) subjects of this group felt this intervention was helpful. Responses regarding effect on the patient's sexual life were poor and 126 (63%) denied answering the question.In our study one third of cancer patients were found to be depressed mainly affecting those who were receiving multimodality treatment or facing financial issues. Religious help was the main coping strategy for them.

Introduction: Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. Methods: A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. Results: A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being . Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/, 34 (26%) one between 100-300 cells/ and 40 (31%) an ANC greater than 300 cells/. Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC were more likely to die than patients with ANC >300 cells/ by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Conclusion: Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

The biliary tract is an unusual site of metastasis from breast carcinoma, and this has rarely been reported in the literature. We report the case of a 42-year-old woman diagnosed with invasive lobular carcinoma of the breast who underwent laparoscopic cholecystectomy for an incidental finding of gallbladder wall thickening on ultrasonography, which was subsequently confirmed to be consistent with metastasis from the breast primary.

To study cardiotoxicities, especially bradycardia in cancer patients treated with 5-Fluouracil and 5-Fluouracil based chemotherapy regimens in Pakistani population.Data was extracted from the medical records of all diagnosed cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Center registered between January 2002 and December 2004 receiving 5- Fluouracil based chemotherapy regimens. The data was analysed retrospectively, including electrocardiogram and cardiac markers. Pearson's Correlation coefficient was calculated to see any possible correlation between 5-Fluouracil alone and 5-Fluouracil based regimens and cardiotoxicity, and other variables.Symptomatic cardiotoxicity was observed in 60 (19.93%) out of 301 patients whose cases were part of the study. Bradycardia was the most common cardiotoxicity and was observed in 36 (11.96%) patients. Nine (2.99%) mortalities were also observed. The incidence of cardiotoxicity was not significantly different between the patients with and without pre-existing cardiovascular disease (p = 0.095) and having negative correlation - 0.305. Cardiotoxicities were more common with Continuous Infusion (CI) of 5-Fluouracil, radiotherapy concurrent with 5-Fluouracil and when 5-Fluouracil was used in combination with Cisplatinum (CDDP).Cardiotoxicities were more prevalent when 5-Fluouracil was used along with concurrent radiotherapy and with Cisplatinum and when administered in continuous infusion pattern. Hence, 5-Fluouracil and 5-Fluouracil based chemotherapy regimens cause cardiotoxicities, especially bradycardia, in a significant number of cancer patients in Pakistani population.

We present our initial experience of allogeneic stem cell transplant procedure performed between April 2004 and August 2011 for various haematological disorders. All patients with non-malignant and malignant haematological disorders with HLA matched donors were selected after pre-transplant workup. Ninety seven patients underwent the procedure. Most common indications for transplant were aplastic anaemia in n = 34 (35%), followed by β-Thalassemia major in n = 21 (21.6%) and chronic myeloid leukemia in n = 11 patients (11.3%). Primary graft failure present was present in 2.06%. Incidence of graft versus host disease (GvHD) in our patients was 34%. After median follow-up of five years the overall survival was 71.3% with a mean survival time of 51.2 ± 3.3 months.

Primary CNS lymphoma (PCNSL) is an aggressive form of non-Hodgkin's lymphoma that accounts for 3% of all primary brain tumours. No clear risk factors for PCNSL in immunocompetent patients are known. The disease is more common in men and in elderly persons. Patients with AIDS who have low CD4+ counts are at the greatest risk for PCNSL. Virtually all PCNSLs in patients with AIDS express an Epstein-Barr virus (EBV)-related genome. PCNSL is less frequently associated with EBV in patients without AIDS. A 42 years old gentleman diagnosed with primary CNS lymphoma with negative serological test for human immunodeficiency virus was initially treated with Modified De Angelis protocol relapsed after treatment. He underwent gamma knife stereotactic surgery which lead to further deterioration clinically and progression of disease on imaging. Later, he was treated with salvage high dose methotrexate, but after completion of six cycles there was a radiological progression of disease. Relapsed disease was further treated with a single agent temozolomide and the disease went in remission.

Hemophagocytic syndrome is a rare disorder mainly affecting children. Symptoms include prolonged fever, hepatosplenomegaly and cytopenias. Allogeneic stem cell transplant appears to provide the best overall cure rate in this disease. The authors report a young boy, the second child of consanguineous parents, diagnosed with familial hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic stem cell transplant form HLA matched father.

Cancer is a cause of major disease burden across the world and Pakistani data suggest that its incidence is increasing. Pakistan's socio-cultural history, social practices, religious beliefs and family systems differ in many ways from rest of the world. These factors make the practice of oncology a challenge.A comprehensive questionnaire focusing on socio-cultural and religious aspects was administered to patients with a diagnosis of cancer and receiving chemotherapy at the Aga Khan University Hospital, Karachi, Pakistan.A total of 230 patients agreed to answer the questionnaire, with a mean age of 46 years and 63% were females. Obtaining some formal education was claimed by 87%, 75.2% had received some treatment before seeing an oncologist, including homeopathic physicians and faith healers. Of all 27 % thought that cancer is contagious, a fact observed more so in those who were illiterate, 27 % believed in some myth such as past sins, evil eye or God's curse as to be cause of their cancer, while 39.6% thought that cancer can be prevented by a regular religious activity. Some 30% thought that a meaningful life after diagnosis of cancer was not possible and 28%considered that they did not have proper information about chemotherapy. About 73% wanted to have their treatment related decision made by the treating physician.Patient related beliefs in myths and concerns are unique in the socio-cultural set up of Pakistan. If physicians are better aware of these factors, they may be able to handle patient related issues in a more effective way.

To determine the complication rate of (PICCs) peripherally inserted central catheters in cancer patients with a 1 year prospective cohort study.All PICCs inserted in adult cancer patients in Radiology Department of The Aga Khan University Hospital were followed prospectively till removed or patient expired and pattern of complications noted.One hundred and fourty six PICCs were inserted over a period of 1 year and followed for a total of 3329 catheter-days; median placement, 14 days: range 3-218 days. Of these 67 (32.8%) PICCs were complicated and removed earlier, for a rate of 14.4/1000 PICC-days. Patients with haematologic malignancies were more likely to have complications as compared to those with solid tissue malignancies.Despite a significant complication rate, PICCs are a relatively safe and cost effective method of establishing central venous access.

In last two decades newer therapies in cancer treatment have emerged and have opened new horizons. New term of targeted therapy has emerged and for certain malignancies the paradigm has really changed after the introduction of these agents. We have learnt and have seen the outcome of some diseases after the addition of these monoclonal antibodies (MoABs) and tyrosine kinase inhibitors (TKIs). Rituximab a MoAB against CD-20 has really paved its role in the treatment of B-cell lymphomas and become the sort of standard therapy. The TKIs are newer agents available in a pill form and have inhibited many pathways at cellular level which are necessary for cancer development. Imatinib has really changed the prognosis and outcome of chronic myeloid leukemia (CML) remarkably. For those patients who develope intolerance to imatinib or their disease became resistant to the imatinib the newer agents like dasatinib and nilotinib are second line options. The major edge of these newer agents is more potency with low side-effect profile. The major concern remains the cost.

Gallbladder cancer (GBC) is a common malignancy in our country; however, very limited data exist on this malignancy in Pakistan.This is a retrospective analysis of all the admitted patients diagnosed with GBC or cholangiocarcinoma in between 1st January 1995 to 31st December 2007.A total of 245 patients were admitted with diagnosis of GBC or cholangiocarcinoma. Sixty seven percent were females. Right hypochondrial pain (70.6%) and jaundice (49.8%) were the commonest symptoms, followed by nausea and vomiting (11.8%), weight loss (13%), fever (18.8%), anorexia (9.8%) and ascites (3.3%). Gallstones were seen in 132 (53.9%) patients. Pathological diagnosis was confirmed in 155 (63.2%) patients, adenocarcinoma (94.8%) being the predominant type. Metastasis was seen in 204 (83.3%) patients, with liver and abdominal lymph nodes being the frequent sites of metastasis. Most of the patients presented to the surgeons (42.9%) and gastroenterologists (35.9%) at their first visit. Only 89 (26.3%) patients were referred to medical oncologists and 42 (16.7%) of the patients actually received chemotherapy. The patients who received chemotherapy cisplatin and gemcitabine demonstrated partial responses (40%). Common bile duct stricture was seen in 78 patients and stenting was successful in 73 patients. Fourteen (5.7%) patients are alive to date, one is receiving chemotherapy, and another is alive with advanced disease while 10 patients had incidental diagnosis after surgery. Of all 53.9% of patients have died and 38% are lost to follow up.Most of the patients with biliary cancers present late with advanced disease at our referral tertiary care hospital. Minority of the patients received chemotherapy and most of responses were observed with cisplatin and gemcitabine combination or capecitbine based therapy.

Colon cancer is a common malignancy with its incidence reportedly rising in Asian countries, including Pakistan. There are no comprehensive data available from Pakistan which focus on associations of various factors with long-term survival of colon cancer. We therefore present an analysis of findings from our centre.In this retrospective study adult patients with colon cancer diagnosed through 2000-2003 were included. A comprehensive questionnaire was filled for each individual through review medical and pathology reports. Long term survival data was collected from contactable patients or their relatives.A total of 93 patients were assessed, 57 males and 36 females (M: F= 1.58: 1). Mean age of diagnosis was 54 years. Of the total, 49.5% of the patients had right sided (mortality rate 51.6%), 10.8% had transverse colon, (mortality rate 37.5%), 7.5% had descending colon (mortality rate 66.7%) and 32.2% had sigmoid colon (mortality rate 40.9%) cancers. Stage I disease on diagnosis was found in 16%, stage II in 42.7 (mortality 40 %) and stage III in 41.3% (mortality 70 %). Tumors were well differentiated in 20.2% (mortality 42.9%), moderately differentiated in 61.9% (mortality 43%) and poorly differentiated in 17.9% (mortality 70%). In 36.3% of the patients less than 12 lymph nodes were removed (mortality 55% Vs 43% in patients with12 lymph nodes removed). Margins were free in most patients but a radial margin was reported in only 44%. Most patients had pure adenocarcinoma while a mucinous type differentiation was seen in 19.7%, 3% had signet ring morphology, 1.5% adeno-squamous carcinoma and similar number with neuroendocrine differentiation. Overall 5 year all cause mortality for all stages combined was 46.9%.Colon cancer in Pakistan commonly presents at an advanced stage, there is a male preponderance, and relatively mean younger age at presentation for males is seen. Advanced stage and lymph node involvement along with poorly differentiated pathology, signet ring or mucinous morphology, location in descending colon, positive surgical margins and removal of less than twelve lymph nodes are factors associated with poor long term survival. There is a need to reinforce information about colon cancer and larger studies from the region are needed to confirm the factors analyzed here.

To assess the knowledge and practice of risk factors, symptoms and screening for breast cancer among health care professionals.A cross sectional study was carried out at The Aga Khan University Hospital from January 2008 to March 2008. A total of 336 health care workers including consultants (48), fellows (17), residents (76), medical officers (14), interns (37), nurses (94) and fourth and final year medical students (50) were requested to fill a questionnaire designed to assess the knowledge about the risk factors, signs and symptoms, screening tools, breast self examination (BSE) and treatment.More than two third participants had good knowledge about the risk factors and signs of breast cancer except some dissociation regarding association of menarche status and smoking. Majority was aware of the benefits of mammography. More than 80% had the consensus that breast cancer is curable if detected early and more than 50% thought that a surgeon should be consulted first if lump is palpable.This study reveals that health care professionals have fairly good awareness regarding the risk factors, symptoms and role of mammography. But some are still deficient in their knowledge regarding screening modalities and BSE method and time and role of chemotherapy. And this can be improved with further education.

Targeted agents are now an integral part of treatment regimens for some cancers. Trastuzumab is established in treatment of human epidermal receptor 2 (Her2) positive breast cancers, with improvements in both, the disease free and over all survival. Monoclonal antibody (MoAB) against vascular growth factor receptor (VEGF), bevacizumab and cetuximab a MoAB against epidermal growth factor receptor (EGFR) are establishing their role in a many cancers after making their mark in colorectal cancer. Sorafenib and sunitinib have success stories in renal carcinoma. The Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial has established sorafenib role in advanced hepatocellular carcinoma, while in gastrointestinal tumors; imatinib and sunitinib have proven role. At this point in time side effect profile of all these agents appears relatively safe however cost for developing countries remains an issue.

Cancer is a major cause of disease burden in Pakistan, so that knowledge of physicians about all aspects should be adequate, especially for palliative care for end stage management, given the generally late stage presentation.A cross-sectional study was conducted in three tertiary care hospitals and areas of general practice in Pakistan.A total of 236 non-oncologist physicians were assessed. Most of them claimed to have cared for cancer patients in someway and considered that cancer treatment is often long and protracted. However, one-third were unaware of the fact that cancer is a major disease burden in our society. About half of them thought that chemotherapy makes patients miserable. Oncology as a practice was considered financially of low reward by about a quarter. Most physicians, including consultants, were unaware of the term hospice. Many did not know where to refer cases of cancer and about the commonest cancers in Pakistani males.Awareness about cancer and palliative care among primary physicians needs to be improved for cancer prevention and control.

The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of Diffuse large B-cell lymphoma (DLBCL) patients according to the primary site (extranodal vs. nodal) with applicability of International Prognostic Index (IPI).A retrospective review (1988 to 2004) of 557 cases of DLBC.The median age was 48.7 +/- 15.3 years; M:F ratio was 2:1. The distribution according to the primary site was: lymph node (N-NHL), 322 cases (58%) of which 145(44%) were stage IV, 76(23%) stage III, 60 (18%) stage II and 47 (15%) stage I. The extra nodal sites (EN-NHL) 235 (42%) cases included gastro-intestinal tract (44%), upper aerodigestive tract (19%), bones (8%), spine (5%), and unusual sites less than 3% each as breast, CNS, testis, lungs and skin. The median survival rate was 4.8 years and 6.3 years in N-NHL and EN-NHL respectively. In the latter this varied greatly depending on the primary site and stage of disease at presentation. In the univariate analysis factors associated with good prognosis were: age less than 60 years, early stage (I-II), extranodal involvement primarily gastric or bone, 0-1 extranodal site, 0-1 performance status, lack of B symptoms and normal LDH level. In the multivariate analysis age, performance status, stage of disease and level of LDH were the main variables predicting overall survival; no nodal or extranodal site maintained their prognostic value.Patients with EN-NHL present more frequently with early stage disease then those with N-NHL; overall survival in both groups largely depended on IPI and not on the site of origin of the malignancy.

Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario.A cross-sectional descriptive study was conducted on patients,or =18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007.A total of 80 patients [43 (53.8%) males and 37 (46.2%) females] were selected. The mean age was 47.4 (SD +/-16.6; range 18-79) years. Sixty eight patients (86%) wereor = 65 years, 50% wereor = 50 years. Overall, inhospital mortality was 11%; 4% for patients on granulocyte colony stimulating factor (G-CSF) prophylaxis as against 20% for those without. The cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD +/-3.8; range 2-17) days. Hematological malignancies, older age, severity of dehydration, pneumonia and culture positivity were significantly associated with LOS and death. Those above 50 years of age were 1.5 times as likely to be hospitalized longer andthree times as likely to die. Bacteremia conferred a 5-fold and pneumonia an 8-fold increase in the risk of death.The results of this study indicate that age, vital instability, dehydration, high creatinine, culture positivity and hematological malignancies are high risk factors in chemotherapy induced FN. Identification of FN risk factors with poor outcomes may help in devising protocols for modified dosage or including GCFs initially. This may help reduce the cost of cancer care as well as mortality and morbidity. Prospective studies of FN in multiple centers in Pakistan may be beneficial in evaluating these risk factors further.

Primary Cutaneous lymphomas of B cell origin are rare, there remains a controversy in truly classifying these lymphomas and an updated EORTC classification divides them on the basis of their distinct histopthological grounds rather than on the basis of their anatomic location as in WHO classification, while the new WHO- EORTC joint classification maintains some characteristics of both systems, We report an elderly gentleman who primarily had a typical Leg dominant Cutaneous lymphoma of B cell origin uniquely with involvement of nasal Sinusues, bearing the Immunohistochemical staining features of "Cutaneous lymphoma - Leg Type" befitting the new joint WHO-EORTC classification of Cutaneous B cell Lymphoma.

566 Background: The Asia-Pacific, multicenter, nonrandomized, phase II APEC study previously reported that first-line therapy for pts with KRAS ex 2 wt mCRC consisting of C once every 2 weeks combined with FOLFOX or FOLFIRI achieved efficacy and safety profiles comparable to those reported in analogous pivotal studies involving weekly C. This final analysis presents OS data from the KRAS wt intent-to-treat (ITT) population, as well as subgroup efficacy analyses stratified by BRAF, PIKC3A, and all RAS mutation status. Methods: Eligible pts received C once every 2 weeks (day 1 of each cycle, 500 mg/m2) with FOLFOX or FOLFIRI (investigator’s choice). Study treatment continued until disease progression, dose-limiting toxicity or consent withdrawal. The primary endpoint was best confirmed overall response as assessed by RECIST 1.0; progression-free survival (PFS) and OS were secondary endpoints. In the evaluable populations, the status of BRAF, PIK3CA, and all RAS mutations was assessed retrospectively by pyrosequencing. Results: 42 months after the last patient was enrolled, median OS in the KRAS wt population was 26.8 months (Table). There were no unexpected safety findings. Additional biomarker results—including objective response rate (ORR), PFS, and OS subgroup analyses stratified on BRAF, PIKC3A, and all RAS mutation status—will be presented. Conclusions: The observed median OS of 26.8 months in the KRAS wt population is comparable to that reported in prior pivotal studies involving weekly C plus FOLFOX or FOLFIRI in the first line. These results suggest that C plus FOLFOX or FOLFIRI in a once-every-2-weeks regimen is active and tolerable as first-line therapy in this Asia-Pacific study population and a convenient alternative to weekly administration. Clinical trial information: NCT00778830. [Table: see text]

5-Fluorouracil (5-FU) is an active chemoetheraputic agent in many malignancies, used both in the curative and metastatic setting. Therefore, the side effect profile of 5-FU is well-described and recognized. Here, we present a case of a 28-year-old male, who received 5-FU and carboplatin concurrently, with radiation, for esophageal carcinoma. On Day 3 of his 5-FU infusion, he developed simultaneous cardiac arrhythmias, renal dysfunction, and aphasia. Magnetic resonance imaging (MRI) of his brain revealed acute demyelination of the white matter corresponding to diffusion restriction, pointing toward a small vessel injury. The 5-FU infusion was promptly discontinued and stress dose steroids were administered. The patient's symptoms resolved rapidly with no residual effects. We believe this is the first case of multisystem, small-vessel, vasculopathy secondary to 5-FU. Early recognition and prompt discontinuation of the offending drug is essential for resolution of symptoms. Steroids, with their anti-inflammatory effects can aid in rapid recovery.

PURPOSE/OBJECTIVES To examine the effect of exercise and methylphenidate on fatigue, functional ability, and cognitive function in patients with melanoma. DESIGN Pilot study with comparison to historic controls. SETTING University-based cancer center. SAMPLE 12 patients with melanoma entered and completed the study. The mean age was 44 years. METHOD Eligible patients were recruited before their first dose of interferon-a (IFN-a). Patients were instructed to take 20 mg sustained-release methylphenidate every morning and follow an aerobic exercise program four days a week for 15-30 minutes. Measures included a 12-minute walk, the Schwartz Cancer Fatigue Scale, Trail Maker Forms A and B, Medical Outcomes Study 36 Short Form, body weight, and daily logs. Fatigue scores were compared to usual care historical controls with melanoma receiving only IFN-a. MAIN RESEARCH VARIABLES Fatigue, functional ability, and cognitive function. FINDINGS 66% adhered to exercise and methylphenidate; all adhered to exercise. Fatigue was lower for the exercise and methylphenidate group than historic controls. Functional ability increased 6% for all patients and 9% for the exercise and methylphenidate group. Cognitive function was stable for the exercise and methylphenidate group. The exercise-only group showed marked cognitive slowing. CONCLUSION The combination of aerobic exercise and methylphenidate may have a positive effect on fatigue, cognitive function, and functional ability. A larger sample size and randomized trial is needed to more rigorously evaluate the results of exercise and methylphenidate alone or in combination. IMPLICATIONS FOR NURSING Although further study is needed, a combination of exercise and methylphenidate may be a practical intervention for patients receiving IFN-a for melanoma.

Advanced mycosis fungoides (MF) is incurable with conventional treatments. High-dose chemoradiotherapy with autologous bone marrow transplantation has induced remissions in a small number of patients with MF, but this modality is limited by a high relapse rate. We report induction of complete remission in a 37-year-old woman with rapidly progressive stage IV MF with allogeneic stem cell transplantation (Allo SCT). She remains in continuous complete remission 2 years after transplant. Allo SCT for MF is theoretically attractive, because there is no contamination of the graft by malignant cells, and because of the possibility of graft-versus-tumor effect. Although the results in this patient are encouraging, more patients and longer follow-up are needed to define the usefulness of Allo SCT in the treatment of MF.

Background Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones. Methods This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted. Results Out of 93 newly diagnosed patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed patients, 5 had soft tissue sarcoma and 9 had bone sarcoma. Mean age was 32.5 years. At presentation, approximately two third patients had localised disease while remaining one third had metastatic disease. The Kaplan Meier estimate of median recurrence free survival was 25 months, 35 months, and 44 months for Osteogenic sarcoma, Ewing's sarcoma and Chondrosarcoma respectively. For Leiomyosarcoma and Synovial sarcoma, it was 20 and 19 months respectively. The grade of the tumour (p = 0.02) and surgical margin status (p = 0.001) were statistically significant for determination of relapse of disease. Conclusion The median recurrence free survival of patients in our study was comparable to the reported literature but with significant lost to follow rate. Further large-scale, multi centre studies are needed to have a more comprehensive understanding of this heterogeneous disease in our population.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Hepatobiliary Cancers address hepatocellular cancer, cancer of the gallbladder, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma. Hepatocellular cancer incidence is higher in the Middle East and North Africa (MENA) region than in the West, and hepatitis B and C infections are particularly important; the incidence of gallbladder cancer is among the highest in the world. Regional problems include delay in diagnosis, shortage of trained staff, and insufficient liver transplant facilities. Furthermore, costs associated with molecular and targeted therapies are an increasing concern. A committee was formed, consisting of leading specialists and decision-makers from the region, with each member being tasked to suggest modifications to the existing guidelines based on review of the literature and consultations with local colleagues. This committee met as a group, and then continued to discuss and debate the suggested modifications electronically. Several recommendations were finalized after vigorous debate. The final approved recommendations were then presented in April 2009 to the chair of the NCCN Hepatobiliary Cancers Panel for onward transmission and approval. This project represents an effort to modify and implement the NCCN Guidelines on Hepatobiliary Cancers in the MENA region, while taking into consideration local differences in patient and disease characteristics. The hope is that this will form the basis of future local, regional, and international cooperation in guideline development and research.

e20586 Background: Febrile neutropenia (FN) and myelosupression remain a challenging oncologic medical emergency and dose limiting toxicity of chemotherapy. Various factors have been studied to be associated and affect outcome of patients admitted with FN. Electrolyte abnormalities have commonly been observed, but the real incidence and impact has been only scarcely studied. This study was conducted with the aim to observe the trends of electrolyte abnormalities seen synchronously in patients admitted with chemotherapy induced febrile neutropenia and their possible influence on the outcomes. Methods: This was a prospective, observational study. A total of 215 patients admitted with FN between January 2007 and August 2008 were included. Analysis of data was made using SPSS version16.0. Toxicity profile was graded according to CTC version 3.0. Results: Febrile neutropenia was seen to be almost equally distributed among patients with solid or hematological malignancies. Males and females were seen to be affected almost equally as well. A total of 83.5% patients demonstrated some degree of electrolyte abnormalities. Hypokalemia, of any grade, was seen in 48% of patients, 51.4% having grade I, 33.3% grade III and 15.2% had grade IV hypokalemia. Hyponatremia of all grades was seen in 67.9% patients, 60.3% had Grade I, 33.3% grade III and 0.7% patients had grade IV hyponatremia. Hypomagnesaemia was seen in 54.3% patient, 94.7% having grade I decline. About 12% of patients with electrolyte deficit also had a co-existing Vomiting or diarrhea or both. Average length of stay was 5.7 days in patients having coexisting electrolyte abnormalities, compared to 4.2 days in those who had not. Out of 90 patients who requires special care unit 75 had electrolyte abnormalities, of 15 patients who expired 13 had electrolyte abnormalities. Conclusions: This analysis, which is perhaps first of its kind, suggests that electrolyte abnormalities are frequently observed in patients presenting with FN, independent of co existing vomiting or diarrhea. They can have a negative affect on the outcome such patients. Therefore the incidence and impact of electrolytes abnormalities on FN outcomes should be elaboratively studied further. No significant financial relationships to disclose.

e20716 Background: Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario. Methods: A cross-sectional descriptive study was conducted on patients, >18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007. Results: A total of 80 patients [43 (53.8%) males and 37 (46.2%) females] were selected. The mean age was 47.4 (SD ±16.6; range 18–79) years. Sixty eight patients (86%) were < 65 years, 50% were < 50 years. Overall, in hospital mortality was 11%; 4% for patients on granulocyte colony stimulating factor (G-CSF) prophylaxis as against 20% for those without. The cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD ±3.8; range 2–17) days. Hematological malignancies, older age, severity of dehydration, pneumonia and culture positivity were significantly associated with LOS and death. Those above 50 years of age were 1.5 times as likely to be hospitalized longer and > three times as likely to die. Bacteremia conferred a 5-fold and pneumonia an 8-fold increase in the risk of death. Conclusions: The results of this study indicate that age, vital instability, dehydration, high creatinine, culture positivity and hematological malignancies are high risk factors in chemotherapy induced FN. Identification of FN risk factors with poor outcomes may help in devising protocols for modified dosage or including GCFs initially. This may help reduce the cost of cancer care as well as mortality and morbidity. Prospective studies of FN in multiple centers in Pakistan may be beneficial in evaluating these risk factors further. No significant financial relationships to disclose.

Background & Objective: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of Diffuse large B-cell lymphoma (DLBCL) patients according to the primary site (extra nodal vs nodal) with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 711 cases of NHL were diagnosed at our Institute. Out of these 145 (20%) patients were excluded as they were other than DLBCL hitopathology. Five hundreds fifty-seven (80%) patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Ann Arbor staging system was used for staging with bone marrow biopsy, chest and abdominal radiography/CT. Results: Median age was 48.7 ± 15.3 years; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I; and EN sites, 235 (42%), including gastro-intestinal tract (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and unusual sites less than 3% each as breast, CNS, testis, lungs and skin. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I -II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI.

17542 Background: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of DLBCL patients according to the primary site with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 557 patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Results: Median age was 48.7 ± 15.3 years ; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I ; and EN sites, 235 (42%), including GIT (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and 3% each as breast, CNS, testis,lungs. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I-II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI. No significant financial relationships to disclose.

Introduction Cisplatin is a platinum compound that has revolutionized the treatment of various solid organ tumors. Cisplatin is associated with a variety of side effects and has recently been indicted in the development of posterior reversible encephalopathy syndrome. Posterior reversible encephalopathy syndrome is a potentially reversible condition, with the mainstay of therapy being correction of the underlying cause and withdrawal of the offending drug. However, there are no clear guidelines regarding the possibility of subsequent re-treatment with the causative agent. Case presentation A 23-year-old Asian man presented to our Emergency Department with a four-month history of concomitant abdominal pain and backache and a two-week history of left-sided leg swelling. Diagnostic investigations revealed bilateral pulmonary embolism, extensive deep venous thrombosis and widespread lung and liver metastatic deposits with abdomino-pelvic lymphadenopathy. His biopsy and tumor markers were consistent with non-seminomatous germ cell tumor and he was subsequently started on an initial cycle of cisplatin and etoposide chemotherapy. On the second day of treatment he developed posterior reversible encephalopathy syndrome clinically and radiologically. Cisplatin was stopped for the next two days while etoposide was continued, resulting in complete resolution of his symptoms. He was re-challenged with cisplatin on day five of chemotherapy because a platin-based chemotherapy regimen was his only hope of potential cure. He tolerated it well, with no recurrence of his neurological symptoms and the remainder of his in-patient stay remained uneventful. He was discharged on day eight. He has since then completed treatment and is currently in remission. Conclusions The occurrence of posterior reversible encephalopathy syndrome after cisplatin use has been well reported in the literature. We strongly believe that our patient also developed posterior reversible encephalopathy syndrome secondary to cisplatin. The uniqueness of our patient’s case lies in the successful re-treatment of our patient with the offending drug. To the best of our knowledge, this is the first instance where a patient was successfully re-treated with cisplatin after having developed posterior reversible encephalopathy syndrome as a result of cisplatin use. The excellent response to re-treatment without recurrence of neurological symptoms in our patient’s case provides insight into re-treatment as an option in scenarios where treatment options are limited.