Regional variation in identified cancer care needs of early-career oncologists in China, India, and Pakistan.

BACKGROUND: Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. METHODS: A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. RESULTS: A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in cancer-specific care and palliative care, Indian respondents favored improved cancer detection and advancing research in cancer care, and Pakistani respondents prioritized awareness of cancer and improvements in disease detection and cancer care research. For all, the most frequently cited opportunity was help in improving professional cancer education and training. CONCLUSION: Predominantly early-career oncologists attending clinical research workshops (in China, India, and Pakistan) identified needs for increasing clinical cancer research, professional education, and public awareness of cancer. Decision makers supporting efforts to reduce the burden of cancer worldwide will need to factor the specific needs and aspirations of health care providers in their country in prioritizing health policies and budgets.

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country.

PURPOSE: To highlight challenges and cancer care disparities in patients of diffuse large B-cell lymphoma management in resource-constrained settings. MATERIALS AND METHODS: This multicenter retrospective study included 738 patients from 12 public and private sector hematology-oncology centers across Pakistan. Patients were divided into limited-resource and enhanced-resource settings as per national diffuse large B-cell lymphoma (DLBCL) guidelines. RESULTS: The median age at diagnosis was 47 years (range, 14-89). Male:female ratio was 2.5:1. Majority of the patients (69.3%) were treated in limited-resource settings. Computed tomography was used as a staging modality in 442 (60%) patients. Limited-stage DLBCL was present in 13.5% of patients, while 86.3% had advanced-stage disease at diagnosis. First-line regimens included rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in 56% and cyclophosphamide, doxorubicin, vincristine, prednisone in 34% of patients, while 10% of patients received palliative regimens upfront. Of evaluable data, complete remission was documented in 299 (74.4%) patients, 39 (9.8%) had partial response and 63 (13.5%) had progressive disease. Disease-free survival (DFS) and overall survival (OS) status were not available for 345 (46.8%) patients at the time of data collection. Overall study cohort had a median follow-up of 2.2 years with a median OS of 3.6 years (95% CI, 3.1 to 4.1), median DFS of 3.1 years (95% CI, 2.6 to 3.6), and a 5-year OS of 40% and DFS of 36%. CONCLUSION: Patients from low- and middle-income countries present at an earlier age and have more advanced disease. Patients were frequently lost to follow-up, and record keeping was inadequate more so in patients treated in limited-resource settings. There is a need to establish a national lymphoma registry, improve record keeping, and standardize treatments to ensure improvement in treatment outcomes.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Challenges in Access to New Therapeutic Agents: Marginalized Patients With Cancer in Pakistan and the Need for New Guidelines.

PURPOSE: Cancer care disparities persist among the medically underserved patients with cancer in Pakistan. To determine the access that marginalized patients with cancer have to chemotherapy and newer targeted agents in Pakistan approved by essential medicine list 2017, the barriers that patients face in getting such access, the implications of the barriers for the effectiveness of treatment, and ways of overcoming those barriers, with particular attention to breast cancer (BC), diffuse large B-cell lymphoma (DLBCL), and chronic myeloid leukemia (CML), need to be addressed. METHODS: A cross-sectional survey of 28 private and public cancer centers targeting more than 50% of patients with cancer for year 2018 was conducted with focus on access to optimal therapy for BC, DLBCL, and CML. To assess the impact of socioeconomic status on the effectiveness of treatment, patients were categorized into three main income groups-low, middle, and high according to gross domestic product per capita on the basis of which some patients were categorized as economically marginalized. Differences in quality of care in public and private sector hospitals were assessed by optimal delivery and completion of chemotherapy on the basis of international guidelines. Access to optimal dose and timings of targeted therapies were determined. RESULTS: In our marginalized patients, 30%-40% received optimal basic chemotherapy for BC and DLBCL. Less than 10% of patients with human epidermal growth factor receptor 2-positive BC completed 17 cycles of trastuzumab within 12 months. For DLBCL, hardly any patients received concurrent rituximab with chemotherapy for six cycles. Dose delays, modifications, and abandonment of treatment occurred in approximately 50% of the marginalized patients. In patients with CML, the compliance to imatinib/nilotinib was 85%. CONCLUSION: Significant barriers exist in providing optimal basic and targeted therapies to our indigent patients despite government funding and availability of access programs.

"Outcomes of COVID-19 infection in patients with hematological malignancies- A multicenter analysis from Pakistan".

PURPOSE: COVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy. PATIENTS AND METHODS: This multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals in Pakistan from February to August 2020. A patient with any known hematological malignancy who was positive for COVID-19 on RT-PCR, was included in the study. Chi-square test and Cox-regression hazard regression model was applied considering p ≤ 0.05 significant. RESULTS: A total of 107 patients with hematological malignancies were diagnosed with COVID-19, out of which 82 (76.64%) were alive, and 25 (23.36%) were dead. The significant hematological malignancy was B-cell Lymphoma in dead 4 (16.00%) and alive group 21 (25.61%), respectively. The majority of the patients in both the dead and alive group were on active treatment for hematological malignancy while they came positive for COVID-19 [21 (84.00%) & 48 (58.54%) p 0.020]. All patients in the dead group were admitted to the hospital 25 (100.00%), and among these, 14 (56.00%) were admitted in ICU with a median 11 (6-16.5) number of days. Among those who had contact exposure, the hazard of survival or death in patients with hematological malignancies and COVID-19 positive was 2.18 (CI: 1.90-4.44) times and 3.10 (CI: 2.73-4.60) times in patients with travel history compared to no exposure history (p 0.001). CONCLUSION: Taken together, this data supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection.

A Multicenter Study of Clinical Presentations and Outcomes of Multiple Myeloma in Pakistan: The Real-World Analysis in a Resource-Constrained Country.

This is the first multicenter study from Pakistan exploring the prevalence, clinical presentations and treatment outcomes of Multiple Myeloma patients. This retrospective study involved data collection from hospital record system of four tertiary care referral hospitals of Pakistan including all patients diagnosed as having Multiple Myeloma from January 2014 to December 2018. The demographic details, clinical presentations, laboratory findings, treatment responses, and mortalities were evaluated. The progression-free survival and overall survival were analyzed considering relapse and mortality as the end points, respectively. For the progression-free survival, the Kaplan-Meier survival analysis and the log rank test were used to compare the survival function for chemotherapy followed by autologous stem cell transplant (ASCT) as opposed to chemotherapy alone (non-ASCT). The overall survival analysis was assessed by Kaplan-Meier survival analysis. This study identified 403 Multiple Myeloma patients in five years. The median age at presentation was 55 years. Bortezomib based drug regimens were the most commonly used initial treatments (57.5%). Forty three patients received ASCT. The progression-free survival median for ASCT and non-ASCT patients were 50 months (95% CI, 42-57.9 months) and 26 months (95% CI, 21.5-30.5 months), respectively. The cumulative probability of survival rate at 60 months was 80%. This study identified 403 Multiple Myeloma patients over 5 years in four tertiary care hospitals of Pakistan. It underscores the importance of autologous stem cell transplant in Myeloma patients and advocates improving its facilities in Pakistan.

Cancer medicines on the WHO Model List of Essential Medicines: processes, challenges, and a way forward.

The selection of cancer medicines for national procurement requires deliberate evaluation of population benefit, budget impact, sustainability, and health system capacity. However, this process is complicated by numerous challenges, including the large volume and rapid pace of newly developed therapies offering marginal gains at prohibitively high prices. The WHO Model List of Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc) have undergone a series of evidence-based updates to ensure recommended cancer medicines offer meaningful clinical benefit. This Health Policy paper describes how cancer medicines are listed on the EML and EMLc, including two updated WHO processes: (1) the formation of the Cancer Medicines Working Group, and (2) additional selection principles for recommending cancer medicines, including a minimum overall survival benefit of 4-6 months with improvement to quality of life compared with standard treatment. These updates, along with proposals to include formal price considerations, additional selection criteria, and multisectoral collaboration (eg, voluntary licensing) promote procurement of high-value essential cancer medicines on national formularies in the context of supporting sustainable health systems to achieve universal health coverage.

Assessment of Adult Women With Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource-Stratified Guideline.

PURPOSE: To provide expert guidance to clinicians and policymakers in three resource-constrained settings on diagnosis and staging of adult women with ovarian masses and treatment of patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer. METHODS: A multidisciplinary, multinational ASCO Expert Panel reviewed existing guidelines, conducted a modified ADAPTE process, and conducted a formal consensus process with additional experts. RESULTS: Existing sets of guidelines from eight guideline developers were found and reviewed for resource-constrained settings; adapted recommendations from nine guidelines form the evidence base, informing two rounds of formal consensus; and all recommendations received ≥ 75% agreement. RECOMMENDATIONS: Evaluation of adult symptomatic women in all settings includes symptom assessment, family history, and ultrasound and cancer antigen 125 serum tumor marker levels where feasible. In limited and enhanced settings, additional imaging may be requested. Diagnosis, staging, and/or treatment involves surgery. Presurgical workup of every suspected ovarian cancer requires a metastatic workup. Only trained clinicians with logistical support should perform surgical staging; treatment requires histologic confirmation; surgical goal is staging disease and performing complete cytoreduction to no gross residual disease. In first-line therapy, platinum-based chemotherapy is recommended; in advanced stages, patients may receive neoadjuvant chemotherapy. After neoadjuvant chemotherapy, all patients should be evaluated for interval debulking surgery. Targeted therapy is not recommended in basic or limited settings. Specialized interventions are resource-dependent, for example, laparoscopy, fertility-sparing surgery, genetic testing, and targeted therapy. Multidisciplinary cancer care and palliative care should be offered.Additional information can be found at www.asco.org/resource-stratified-guidelines. It is ASCO's view that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

AIM: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial. PATIENTS AND METHODS: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac). RESULTS: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups. CONCLUSION: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00490139.

Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

Sustained superior long-term outcomes and cytogenetic responses with imatinib mesylate in chronic phase chronic myeloid leukaemia: report from a developing country.

OBJECTIVE: Imatinib mesylate is now a standard treatment for chronic myeloid leukaemia. Primary objective of our study was to report long-term survival outcomes in patients receiving Imatinib in chronic phase. Secondary objectives included determination of cytogenetic responses and toxicity profile of Imatinib mesylate. METHODS: Three-hundred and four consecutive patients with chronic phase chronic myeloid leukaemia were evaluated between January 2001 to December 2007, for event-free survival, overall survival, complete cytogenetic response and toxicity profiles. Event-free and overall survivals were calculated by Kaplan-Meier estimates. Cox regression analysis was performed to evaluate the prognostic factors for survival. Univariate and multivariate analyses were performed for factors predictive of a complete cytogenetic response. RESULTS: Median follow-up was 48 months. Estimated 5-year event-free and overall survivals of all patients were 79% and 86%, respectively. On Cox regression analysis significant predictive factors for event-free survival were age < 50 years (P 0.002), complete cytogenetic response (P < 0.0001), low Sokal score (P 0.007), complete clinical (P < 0.0001) and haematological response (P < 0.0001). Complete cytogenetic response was achieved in 206 (67.8%) patients. On multivariate analysis, low Sokal score (P < 0.0001) and early chronic phase disease (P < 0.0001) emerged as the most significant predictors for achieving a complete cytogenetic response. An estimated 5.8% patients lost their complete cytogenetic response. Grade III/IV toxicity was observed in only 21 patients. CONCLUSIONS: Long-term treatment with Imatinib mesylate results in superior and durable responses in chronic phase chronic myeloid leukaemia. Our survival outcomes are similar to reported rates in the Western population.

Survival of women with locally advanced breast cancer at a teaching hospital in Lahore.

OBJECTIVES: To correlate the clinical features of women presenting with locally advanced breast cancer with event-free survival (EFS) and overall survival (OS) and to evaluate the patterns of relapse. METHODS: A total of 200 patients presenting consecutively over 9 years with Stage III breast cancer were evaluated for age, socio-economic status (SES), tumour size and grade, number of involved lymph nodes, stage III sub-categories, estrogen and progesterone receptor (ER/PR) status, treatment profiles and responses, and sites of relapse. EFS and OS at 5 and 10 years were calculated. RESULTS: Median age was 45 years. Poorly differentiated tumours were found in 127 patients, while 128 had larger tumours (T3 and T4). Eighty women had extensive nodal involvement (N2 and N3), and 86 had Stage IIIA tumours. Chemotherapy was given to 44 patients before surgery and one of these patients achieved pathological complete response. At 5 and 10 years, EFS was 25% and 7%, and OS was 52% and 31%, respectively. By Cox regression analysis, significant predictors of EFS included tumour size (95% CI 1.14-1.72), nodal involvement (95% CI 1.06-1.59) and ER/PR positive tumours (95% CI 1.08-2.29). Predictors of OS included nodal involvement (95% CI 0.98-3.3) and ER/PR positive tumours (95% CI 1.08-2.29). No patient in stage IIIC was alive at 10 years. Loco-regional disease was the most common site of relapse (28.5%). CONCLUSIONS: Locally advance breast cancer at our centre is associated with poor survival, and most patients relapsed by 5 years.

Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a clinical management problem after treatment with highly emetogenic chemotherapy (HEC). We therefore designed and carried out a multicentre, randomised, double-blind, placebo-controlled trial to assess whether a three-drug antiemetic regimen of ondansetron, dexamethasone, and the neurokinin-1-receptor antagonist casopitant mesylate was able to prevent acute and delayed CINV events in patients naive to chemotherapy with a malignant solid tumour who were scheduled to receive cisplatin-based HEC regimens. METHODS: The study was done between Nov 6, 2006, and Oct 9, 2007, in 77 participating centres in 22 countries. All 810 patients enrolled in the trial received dexamethasone and ondansetron. Patients were randomly assigned to also receive placebo (n=269), single oral dose of casopitant mesylate (150 mg oral, n=271), or 3-day intravenous plus oral casopitant mesylate (90 mg intravenous on day 1 plus 50 mg oral on days 2 and 3, n=270). Randomisation was done using a central telephone system at the study level, because some centres were expected to recruit only a few patients during the study period. The primary endpoint was the proportion of patients achieving complete response (no vomiting, retching, or use of rescue medications) in the first 120 h after receiving HEC. Efficacy analysis was done on the modified intention-to-treat population (n=800), which included all patients who received placebo or study drug and HEC (n=265 control, n=266 single-dose oral casopitant mesylate, n=269 3-day intravenous and oral casopitant mesylate). Safety was reported in 802 patients who received either placebo or study medication. This study is registered with ClinicalTrials.gov, NCT00431236. FINDINGS: Significantly more patients in each casopitant group achieved complete response in cycle 1 of HEC treatment than did those in the control group (175 [66%] patients in the control group, 228 [86%] in the single-dose oral casopitant mesylate group [p<0.0001 vs control], and 214 [80%] in the 3-day intravenous plus oral casopitant mesylate group (p=0.0004 vs control]). This improvement was sustained over multiple cycles of HEC. Adverse events occurred in 205 (77%) patients in the single-dose oral casopitant mesylate group and 203 (75%) patients in the 3-day intravenous and oral casopitant mesylate group compared with 194 (73%) of patients in the control group. The most common serious adverse events were neutropenia (n=5 [3%] in the control group, n=3 [1%] in the single-dose oral casopitant mesylate group, and n=11 [4%] in the 3-day intravenous plus oral casopitant mesylate group), febrile neutropenia (n=1 [<1%] in the control group, n=4 [1%] in the single-dose oral casopitant mesylate group, and n=6 [2%] in the 3-day intravenous plus oral casopitant mesylate group), and dehydration (n=4 [2%] in the control group, n=2 [<1%] in the single-dose oral casopitant mesylate group, and n=1 [<1%] in the 3-day intravenous plus oral casopitant mesylate group). INTERPRETATION: A three-drug regimen including a single oral dose or 3-day intravenous plus oral regimen of casopitant mesylate plus dexamethasone and ondansetron significantly reduced CINV events in patients receiving HEC compared with a two-drug regimen of dexamethasone and ondansetron. FUNDING: GlaxoSmithKline.

Locally advanced breast cancer: treatment guideline implementation with particular attention to low- and middle-income countries.

The management of locally advanced breast cancer (LABC) is guided by scientific advances but is limited by local resources and expertise. LABC remains very common in low-resource countries. The Systemic Therapy Focus Group met as part of the Breast Health Global Initiative (BHGI) Summit in Budapest, Hungary, in October 2007 to discuss management and implementation of primary systemic therapy (PST) for LABC. PST is standard treatment for large operable breast cancer in enhanced-resource settings and, in all resource settings, should be standard treatment for inoperable breast cancer and for LABC. Standard PST includes anthracycline-based chemotherapy. The addition of sequential taxanes after anthracycline improves pathologic responses and breast-conservation rates and is appropriate at enhanced-resource levels; however, costs and lack of clear survival benefit do not justify their use at limited-resource levels. It remains to define better the role of endocrine therapy as PST, but it is acceptable in elderly women. Aromatase inhibitors have produced better results than tamoxifen in postmenopausal patients and are used in enhanced-resource settings. The less expensive tamoxifen remains useful in low-resource countries. Trastuzumab combined with chemotherapy yields high pathologic response rates in patients with HER2/neu-overexpressing tumors; its use in low-resource countries is limited by high costs. Most studies on PST of LABC were conducted in countries with enhanced resources. BHGI encourages conducting clinical trials in countries with limited resources.

Effect of social class disparities on disease stage, quality of treatment and survival outcomes in breast cancer patients from developing countries.

To assess the relationship between social class disparities on disease stage on presentation, quality of treatment, and survival outcome of breast cancer patients in Pakistan and compare our data with SEER (Surveillance, Epidemiology, and End Results) data from US on white and African-American women to evaluate differences in disease stage and survival outcomes. Patients were evaluated for age, tumor size, grade, receptor status, stage, and 5-year survival and were compared with SEER data. Socio-economic status was evaluated with financial income. Patients were divided in poor and middle/high groups. Excellent and comparable 5-year survival with SEER data was observed with localized disease in all groups from different strata. Advanced disease was more common in the disadvantaged group with negligible 5-year survivals. Development and implementation of early detection programs, public awareness, and clinical and breast self examination that are more pragmatic in the settings of countries with limited resources are essential.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

BCR-ABL kinase domain (KD) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-KD mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-KD. Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-KD mutation screening in late chronic phase CML patients for improved clinical management of disease.

Symposium: "Oncology Leadership in Asia".

The symposium on "Oncology Leadership in Asia" was held as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association with International Cancer Conference. Given the increasing incidence of cancer in all countries and regions of Asia, regardless of developmental stage, and also in light of the recognized need for Asian countries to enhance collaboration in cancer prevention, research, treatment and follow-up, the symposium was held with the aim of bringing together oncology specialists from eight countries and regions in Asia to present the status in their own national context and discuss the key challenges and requirements in order to establish a greater Asian presence in the area of cancer control and research. The task of bringing together diverse countries and regions is made all the more urgent in that while Asia now accounts for more than half of all new cancer cases globally, clinical guidelines are based predominantly on practices adopted in Western countries, which may not be optimized for unique ethnic, pharmacogenomic and cultural characteristics in Asia. Recognizing the need for Asia to better gather information and data for the compilation of Asia-specific clinical guidelines, the participants discussed the current status in Asia in the national and regional contexts and identified future steps towards integrated and collaborative initiatives in Asia. A key outcome of the symposium was a proposal to combine and integrate the activities of existing pan-Asian societies, including the Asian Pacific Federation of Organizations for Cancer Research and Control (APFOCC) and Asian Clinical Oncology Society (ACOS). Further proposals included the expansion of pan-Asian society membership to include individuals and the essential need to encourage the participation of young researchers in order to ensure self-sustainability of cancer control efforts in the future.

Prospective evaluation of efficacy and toxicity of 5-fu and folinic acid (Mayo Clinic regimen) in patients with advanced cancer of the gallbladder.

We evaluated the efficacy and toxicity of 5-fluorouracil (5-FU) and folinic acid (Mayo Clinic regimen) in previously untreated patients with advanced gallbladder cancer. Thirty patients with histologically confirmed adenocarcinoma of gallbladder were enrolled on this trial. All were symptomatic and had stage IV disease. Patients received 5-FU 425 mg/m2 daily for 5 consecutive days preceded by folinic acid 20 mg/m2/d. Treatment cycles were repeated every 28 days. Only two patients (7%) achieved an objective response to therapy. Another 10 (33%) had stable disease. Median time to progression was 4.7 months, and median overall survival was 14.8 months. Toxicity was moderate, and one treatment-related death occurred. In conclusion, 5-FU and folinic acid (Mayo Clinic regimen) is ineffective in the management of patients with advanced gallbladder cancer, and further trials with this regimen are not recommended.

Gemcitabine and Cisplatin is a highly effective combination chemotherapy in patients with advanced cancer of the gallbladder.

We evaluated the efficacy and toxicity of gemcitabine with or without cisplatin in 11 chemonaive patients with histologically confirmed advanced gallbladder cancer. All were symptomatic and had stage IV disease. Eight patients received gemcitabine 1 g/m2 on days 1 and 8 along with cisplatin 70 mg/m2 on day 1. Three received gemcitabine alone. Treatment cycles were repeated every 21 days. One patient (9%) had complete remission of disease and 6 (55%) achieved a partial response to chemotherapy with an overall response rate of 64%. Median time to progression was 28 weeks and median overall survival was 42 weeks. Toxicity was easily manageable, and no treatment-related deaths occurred. We conclude that gemcitabine in combination with cisplatin may be one of the most effective therapies for patients with advanced gallbladder cancer. If confirmed by others, it may provide an important therapeutic option in managing these patients who otherwise have a dismal prognosis.

Applicability of international prognostic index in non Hodgkin's lymphoma in Pakistan.

BACKGROUND: Aggressive non Hodgkin's Lymphomas (NHL) are common in Southeast Asia, Middle East and Africa. Data on survival with relation to prognostic factors is scarce. The primary objective of the study was to evaluate the applicability of International Prognostic Index (IPI) to predict overall survival (OS) and disease free survival (DFS) in developing countries. METHODS: Two hundred and nineteen patients of NHL consecutively presenting to the Department of Oncology, Jinnah Hospital Lahore between August 1998 to July 2000 were analyzed. All patients underwent initial staging according to Ann Arbor staging system. The patients were categorized by five independent risk factors: patient age, disease stage, serum lactate dehydrogenase (LDH) levels, performance status, and number of extranodal sites involved. Patients were divided into three risk categories Low (0 or one risk factors), Intermediate (2 risk factors) and High (3 or more risk factors). RESULTS: According to IPI low risk category comprised of 15%, intermediate 21% and high 64% of patients, Overall survival (OS) for 2 years and 5 years (n=197) was (69%), (51%), (32%) and (64%), (46%), (13%) respectively (p=0.0008). Disease free survival (DFS) for 2 years and five years (n=197) was (66%), (43%), (34%) and (66%), (43%), (18%) respectively. Age adjusted (60) DFS for 2 and 5 years (n=164) was (70%), (45%), (40%) and (63%), (45%) (19%) respectively. OS for 2 and 5 years (n=164) was (71%), (52%), (34%) and (64%), (46%), (11%) respectively (p=0.0013). CONCLUSIONS: The IPI accurately predicted survival in our population. Modification of treatment protocols according to specific risk groups will be beneficial to the developing countries with limited resources.