"Hairy Cell Leukemia (HCL): 'Real World' Outcome".

HCL is an uncommon B cell lympho-proliferative disorder with high remission rates. There is paucity of data on the long-term outcome of HCL from India. We retrospectively collected data from individual case records of patients with HCL who were treated in Cancer Institute, Chennai from January 2001 until January 2018. Sixteen patients were diagnosed with HCL and were treated with cladribine (81%), interferon (13%) and one patient received only best supportive care (6%). All the treated patients achieved complete response. More than half of the patients developed febrile neutropenia but there were no treatment related mortality. The 5-year DFS was 77% and 5-year OS was 80%. Relapse of disease was seen in 27%. HCL is a curable malignancy with high remission rates and survival comparable to patient treated in west.

Evaluation of Cytogenetic Abnormalities in Patients with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) accounts for 20% of all adult leukemias and is the most common leukemia during childhood (80%). We present data on cytogenetics of ALL from a tertiary centre in India correlating it with clinical factors. Karyotyping of bone marrow samples of 204 patients with newly diagnosed ALL was performed with standard G-banding technique. Clinical data of patients was obtained from case records. Survival was estimated using Kaplan-Meir curves and compared by the log-rank test. Univariate and multivariate analysis was done for survival with age, sex, immunophenotype, hyperleukocytosis, risk type, remission status and cytogenetics. The most common karyotypes observed were normal in 39.7% (N = 81), hyperdiploidy in 12.7% (N = 26), t(9;22) in 4.4% (N = 9), t(1;19) in 3.9% (N = 8). Adults with ALL had worse survival compared with pediatric patients (HR 3.62; 2.03-6.45 95% CI, p < 0.001). Patients not in morphologic remission after induction chemotherapy fared poorly (HR 4.86; 2.67-8.84 95% CI, p < 0.001). Patients with favourable cytogenetics had better overall survival (HR 0.36; 0.12-1.05 95% CI, p < 0.05). On multivariate analysis, achievement of morphologic remission emerged as single most significant predictor of survival (p < 0.001). MLL gene rearrangement and t(12;21) were seen less commonly as compared to Western data. However, incidence rates of various cytogenetic abnormalities were similar to that reported from other centres from India. Age, morphologic remission at end of induction chemotherapy and favourable cytogenetics correlated significantly with survival.

Real World Experience of Treating Neuroblastoma: Experience from a Tertiary Cancer Centre in India.

OBJECTIVES: Management of neuroblastoma, especially high-risk (HR) disease is difficult in a resource-limited setting. There is a paucity of literature on outcomes of patients treated in India. The present study was conducted to analyse the clinical profile, treatment, and outcomes of patients with neuroblastoma treated at authors' centre. METHODS: The study was a retrospective analysis of newly diagnosed patients with neuroblastoma treated at authors' centre between 2000 to 2017. The International Neuroblastoma Staging System and risk grouping were used to classify patients as low-risk (LR), intermediate-risk (IR) and high-risk (HR). Treatment was individualised and risk-adapted. Kaplan-Meier method was used to calculate the event-free survival (EFS) and overall survival (OS). RESULTS: The study included 85 patients with a median age of 4 y and 67% were males. Malnutrition was observed in 55% of patients. Adrenal gland was the most common site in 75% patients followed by mediastinum in 12%. LR was observed in 7/85 (8%) patients, IR 20/85 (24%) and HR in 58/85 (68%) patients. The CCG-3891 protocol was used to treat 80% of the patients. Autologous stem cell transplantation (ASCT) was performed in 32% of HR patients. The median follow-up was 16.6 mo. The median EFS and OS for all patients were 19.2 mo and 26.9 mo respectively and the 3 y EFS and OS was 36% and 47% respectively. The 3y EFS for LR, IR and HR patients was 100%, 54%, and 18.9% respectively (P < 0.001) and for OS was 100%, 77%, and 34% respectively (P = 0.002). On multivariate analysis, a hemoglobin less than 10 g% predicted inferior EFS (P = 0.002) and OS (p = 0.005) for all patients. For patients with high-risk disease, on multivariate analysis, hemoglobin (P = 0.002) and 13-Cis Retinoic acid maintenance (P = 0.002) predicted EFS and only radiotherapy to the primary (P = 0.01) predicted OS. Only 4/19 (21%) are alive and in remission post ASCT. CONCLUSIONS: Majority of patients with neuroblastoma presented to authors' centre with advanced disease. Survival outcomes of patients with LR disease are excellent. However, patients with HR disease have poor outcomes despite multimodality management. Non-availability of N-MYC testing in few patients could have falsely down-staged them to IR from HR. A low hemoglobin at diagnosis is a poor predictor of outcome.

Efficacy of Single Dose Rasburicase (1.5 mg) for Prophylaxis and Management of Laboratory Tumor Lysis Syndrome.

Rasburicase is a recombinant urate oxidase enzyme approved for use in tumor lysis syndrome (TLS) and it acts by reducing serum uric acid levels. Using rasburicase at the recommended dose of 0.2 mg/kg/day for 5 days is expensive and it is not known whether this extended schedule is clinically beneficial compared to a single fixed dose of 1.5 mg. The aim of the present study was to evaluate the efficacy of single dose rasburicase 1.5 mg in prevention and management of TLS. Rasburicase is available as single use 1.5 mg vial. At our institution a single dose of rasburicase 1.5 mg irrespective of bodyweight has been used in adults and in children a dose of 0.15 mg/kg (maximum 1.5 mg) has been used since 2012 for prevention and management of TLS and subsequent doses are given based on biochemical response and clinical condition. We retrospectively analysed the case records of patients who had received rasburicase from January 2012 to January 2017. The study included 186 patients with hematological malignancies who received rasburicase. Children accounted for 56.4% (n = 105) patients and males comprised 73% (n = 135). Rasburicase was used prophylactically in 59 (31.7%) patients, for laboratory TLS in 76 patients (40.8%) and for clinical TLS in 51 (27.4%) patients. Single fixed dose rasburicase prevented laboratory/clinical TLS in 87% of the prophylactic group and prevented clinical TLS in 72% of the laboratory TLS group. None of the patients in prophylactic and laboratory TLS group developed clinical TLS. However, majority of the patients with clinical TLS required more than one dose rasburicase. Single dose of 1.5 mg (1 vial) rasburicase is efficient in preventing and managing laboratory TLS and is economically viable in resource constrained settings.

Evaluation of a polymorphism in MYBPC3 in patients with anthracycline induced cardiotoxicity.

Cardiotoxicity is the most serious side effect of anthracyclines (doxorubicin, daunorubicin or epirubicin). The incidence of anthracycline induced late cardiac toxicity (AIC) that is overt clinically is 3-5% in the Indian population. Polymorphism in intron 32 (deletion of 25bp) of MYBPC3 has been shown to be present exclusively in Asians and more so in South India (3-8%). The frequency of the polymorphism is significantly higher (13%) in patients with cardiomyopathy in India. Fifteen patients were identified to have cardiac dysfunction following treatment for malignant lymphoma with doxorubicin containing regimens. Peripheral blood DNA from control, amplified by polymerase chain reaction yielded a 467bp fragment while in the presence of the 25bp deletion only a 442bp fragment was detected. To confirm the presence or absence of the polymorphism, amplified DNA was restricted using Bgl1 in all samples. Bgl1 restricted amplified DNA only if the 25bp deletion was absent. A 467 base pair band was observed in all the 15 samples, which suggested the absence of polymorphism in MYBPC3. In a sample of DNA from a patient with a deletion in exon 33 (confirmed by sequencing) a 442bp fragment was detected. Amplified DNA from this patient was not restricted with Bgl1. Wild type MYBPC3 when amplified gave a distinct restriction banding pattern consisting of two bands of 401bp and 66bp. Amplified DNA from all peripheral blood samples restricted with Bgl1 suggesting the absence of the polymorphism. In this preliminary report, MYBPC3 does not seem to play a role in anthracycline induced cardiotoxicity.

Prevalence of multi-drug resistant organisms in stool of paediatric patients with acute leukaemia and correlation with blood culture positivity: A single institution experience.

BACKGROUND: Multi-drug resistant (MDR) bacteria are associated with increased morbidity and mortality in children with acute leukaemia. The present study was conducted to assess the prevalence of MDR bacteria in stool cultures of patients with acute leukaemia at presentation to the hospital. The results were then correlated with blood cultures when patients developed septicaemia. PATIENTS AND METHODS: The study involved analysis of case records of patients with newly diagnosed acute leukaemia less than 18 years of age treated at our centre from January 2015 to December 2015. Stool cultures were sent within 72 hr of hospital admission and blood cultures were sent when clinically indicated. MDR was defined as resistance to at least one antibiotic in three or more following antimicrobial groups: cephalosporins, ß-lactam/ß-lactamase inhibitor, carbapenems, fluoroquinolones and aminoglycosides. RESULTS: The analysis included 85 patients with acute leukaemia, among whom 48 of 85 (56%) patients had positive stool cultures and 42 of 85 (50%) patients were positive for MDR bacteria. Blood cultures were positive in 13 of 48 patients (27%, seven MDR and six non-MDR) with positive stool cultures and three of 37 patients (8%, one MDR and two non-MDR) with negative stool cultures (P = 0.01). The concordance between stool and blood culture for similar organism was 61%. There were seven deaths in 48 stool culture positive patients and two deaths in 37 stool culture negative patients. CONCLUSION: This study shows the high prevalence of MDR bacteria in newly diagnosed children with acute leukaemia. Colonisation with MDR bacteria in stools is associated with increased positivity of blood cultures and mortality.

Comparison study of quality of life in advanced lung cancer patients on tyrosine kinase inhibitor and platinum doublet chemotherapy.

INTRODUCTION: Lung cancer is most common cause of cancer death in the world. Most of the patient are diagnosed in the late stages and receive only palliative treatment. The main objective of the palliative chemotherapy is to improve survival as well as the quality of life (QOL). QOL is the most neglected dimension of cancer care in developing countries like India. Palliative chemotherapeutic agent which has minimum toxicity and prolongs the survival of metastatic cancer patients is the need of the day. MATERIALS AND METHODS: In this study, 43 metastatic adenocarcinoma of lung patients of South Indian origin were enrolled. Twenty patients out of this 43 were epidermal growth factor receptor (EGFR) mutation positive and were started on tyrosine kinase inhibitor (TKI). Rest 23 patients were EGFR mutation negative and were started on various platinum-based doublet chemotherapy. QOL was measured using Cancer Institute QOL Questionnaire version 2 at the beginning of therapy and at the end of 3 months. RESULTS: Our study showed that metastatic lung cancer patients had average QOL at presentation. The QOL in patients on TKI improved compared to those on platinum doublet chemotherapy during the second assessment, but this improvement was statistically not significant. CONCLUSION: In this study, the metastatic lung cancer patients had an average QOL during initial presentation. Patients on TKI had a trend toward better QOL after 3 months of treatment compared to platinum doublet chemotherapy.

The increasing challenge of never smokers with adenocarcinoma lung: Need to look beyond tobacco exposure.

BACKGROUND: Lung cancer continues to remain as one of the leading causes of morbidity and mortality worldwide, despite the decreasing trends in smoking prevalence worldwide. An earlier study from the authors' institute reported the increasing trends of "Nonsmoking associated lung cancers." MATERIALS AND METHODS: All consecutive histologically confirmed patients with lung cancer who presented to the outpatient department over a year (November 2014-October 2015) were included in this current prospective study. RESULTS: Seven hundred and thirteen patients presented with clinicoradiologically suspicious findings of lung cancer in the said period. A pathological confirmation of lung cancer could be ascertained in 495 patients, and this cohort was further analyzed. The mean age of presentation was 57.76 years; the male to female ratio was approximately 2.5:1. Interestingly, 55.35% of the patients were nonsmokers. Adenocarcinoma (63%) was the predominant histology. Never smokers, both among men (P = 0.02) and women (P = 0.001), presented more frequently with adenocarcinoma histology. Further, 84.9% (45/53) of rural and 76.1% (19/25) of urban women who were never smokers reported exposure to indoor air pollution (secondhand smoke/fuel used for cooking purposes) which was significantly associated with adenocarcinoma histology. CONCLUSION: Our study confirmed our initial observation of the changing epidemiology of lung cancer in the Indian subcontinent, paralleling the global trends of rise in adenocarcinoma. Lung cancer in never smokers outnumbering that among smokers was another interesting observation. The take-home message for both the clinicians as well as the policymakers is to study factors beyond tobacco exposure to understand the direction of the current lung cancer epidemic.

Long-term outcome of diffuse large B-cell lymphoma: Impact of biosimilar rituximab and radiation.

INTRODUCTION: Rituximab (R)-CHOP improves survival over CHOP in diffuse large B-cell lymphoma (DLBCL). The availability of biosimilar rituximab in India has increased access of this drug. We report on the impact of treatment on outcomes with special emphasis on the impact of biosimilar rituximab and radiation. METHODS: Outcomes of adults (age 15-60 years) treated with CHOP+/- Rituximab radiation were analyzed retrospectively to look at baseline features, treatment, and event-free and overall survival (EFS and OS). RESULTS: In the period 2000-2013, 444 patients (median age 47 years: 15-60; males: 288 [65%]; Stage III/IV: 224 [50%]; age-adjusted international prognostic index [aaIPI] Score 2 or 3 in 50%) received either CHOP (n = 325 [73%]) or RCHOP (n = 119 [27%]) therapy. Biosimilar rituximab and the original were used in 95 (80%) and 24 (20%) patients, respectively. Radiation was given in 134 (30%) patients (Stages I and II, 100/220 [45%] and Stages III and IV, 34/224 [15%]). After a median follow-up of 46 (0.2-126) months, the 5-year EFS and OS were 59% and 68%, respectively. The factors predicting inferior EFS and OS were age> 40 years, performance status 2-4, Stage III/IV, hemoglobin <12 g/dL, the aaIPI Score 2 or 3, and nonuse of rituximab and radiation. Radiation used in early stage disease benefitted all subgroups regardless of bulky disease, use of rituximab, or the number of cycles of chemotherapy. Addition of rituximab improved survival across all categories of aaIPI. CONCLUSION: Availability of biosimilar rituximab has increased access and survival of patients with DLBCL in India. Radiotherapy improved outcomes in early stages.

Phase II study of interim PET-CT-guided response-adapted therapy in advanced Hodgkin's lymphoma.

BACKGROUND: Combination chemotherapy ABVD (doxorubicin, bleomycin, vinblastine and dacarabazine) cures ∼70% of patients with advanced Hodgkin's lymphoma (aHL, stages IIB, III and IV) while more toxic escalated BEACOPP (EB, combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone) increases cure rates to 85%. Patients with a positive interim positron emission tomography-computerized tomography (PET-CT) scan after two cycles (PET-2) of ABVD have very poor outcomes with continued ABVD. Intensifying therapy with EB in PET-2-positive patients ('response-adapted therapy') may improve cure rates, whereas the negative patients can continue ABVD alone. PATIENTS AND METHODS: Eligible patients with newly diagnosed aHL received two cycles of ABVD and underwent PET-2 (scored with semi-quantitative 5-point visual criteria, 'Deauville score'). PET-2-negative patients continued four additional cycles of ABVD, whereas PET-2-positive patients received four cycles of EB. A phase II sample size of 50 was estimated keeping the lower and higher proportion of rejection of the event-free survival (EFS) as 70% and 85%, respectively. RESULTS: Fifty patients [median age 28 (12-60) years; male : female: 39 : 11; stages: IIB-3 (6%), III-29 (58%) and IV-18 (36%); International Prognostic Score (IPS): 0-3: 34 (68%); 4-7: 16 (32%)] were enrolled; 49 underwent PET-2. Eight (16%) were PET-2-positive, whereas 41 (84%) were negative. Forty-seven were evaluable for EFS and all 50 for overall survival (OS). The 2-year EFS was 76% (95% CI: 68-83) and OS was 88% (95% CI: 82-94). PET-2 was strongly prognostic-2-year EFS, negative versus positive: 82% versus 50%; P = 0.013. CONCLUSION: PET-2 response-adapted strategy could not achieve EFS of 85% in aHL. However, escalated therapy improved outcomes in PET-2-positive patients compared with historical data. TRIAL REGISTRATION: CTRI/2012/06/002741 (http://www.ctri.nic.in) and NCT01304849 (http://www.clinicaltrials.gov).

Dual surrogate markers for rapid prediction of epidermal growth factor receptor mutation status in advanced adenocarcinoma of the lung: A novel approach in resource-limited setting.

INTRODUCTION: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Amplified refractory mutation system (ARMS)-reverse transcription-polymerase chain reaction (RT-PCR), the current standard for detecting EGFR mutation status is time-consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource-limited settings. MATERIALS AND METHODS: Eighty-five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT-PCR method. Immunohistochemical (IHC) was performed using the phosphorylated AKT (P-AKT) and thyroid transcription factor-1 (TTF-1) on above patient's sample, and the results were compared with EGFR mutation tests. RESULTS: EGFR mutation was positive in 34 of 85 patients (40%). P-AKT and TTF-1 were positive in 50 (58.8%) and 68 (80%) patients respectively. Both P-AKT and TTF-1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P-AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF-1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P-AKT and TTF-1 simultaneously. CONCLUSION: P-AKT and TTF-1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy.

Nutritional profile of pediatric cancer patients at Cancer Institute, Chennai.

BACKGROUND: Malnutrition is widely prevalent in the pediatric population in India. There is paucity of data on the prevalence of malnutrition in pediatric cancer patients and the impact of cancer treatment on nutritional status of Indian children. AIMS: The study was conducted to look at the prevalence of malnutrition and assess the impact of treatment on nutritional status of pediatric cancer patients. SETTINGS AND DESIGN: This was a retrospective study. MATERIALS AND METHODS: Data on the weight of pediatric cancer patients <16 years of age treated at Cancer Institute, Chennai, from January 2013 to May 2014 were analyzed at systematic time points in therapy. Patients' weight were plotted on the Centre for Disease Control (CDC) growth charts. Patients were defined to be undernourished if their weight for age was ≤3rd centile in CDC growth charts and obese if their weight for age was ≥97th centile on CDC growth charts. RESULTS: A total of 295 patient case records were analyzed. Acute lymphoblastic leukemia was the most common malignancy. At diagnosis, under-nutrition was seen in 44% patients, this increased to 46% midway during treatment (end of induction in acute leukemia and completion of 50% of planned treatment in solid tumors) and decreased to 27% at the end of treatment (beginning of maintenance in acute leukemia and completion of planned treatment in solid tumors) (P = 0.0005). There was no significant difference in nutritional status between patients with hematological malignancies and solid tumors (P = 0.8). CONCLUSION: Under-nutrition is present in close to half of the pediatric cancer patients presenting to our institute. Active nutritional intervention and education were able to significantly reduce the prevalence of under-nutrition in patients at the end of treatment.

Gastrointestinal stromal tumor: analysis of outcome and correlation with c-kit status in Indian population.

AIMS: The aim of the present study is to analyse the outcome and genotypic pattern of metastatic GIST patients which is largely unknown in India. MATERIALS AND METHODS: The present study was a retrospective analysis of 24 patients of metastatic GIST. The case records were analysed for clinical profile, treatment response and prognostic factors. The archival samples were retrieved for c-kit mutation analysis in all but 5 patients for mutation analysis. RESULTS: The median age of the study population was 56 years. At a median follow up of 29 months, the PFS was 45% at 2 years. Activating c-kit mutations were detected in 10 cases (52.6%). 80% of the mutations were located in Exon 11. CONCLUSIONS: The outcome of metastatic GIST patients has definitely improved from a virtually incurable state to a disease where median OS has reached 60 months. The genotype of Indian patients with GIST may be different from the western population which needs to be confirmed in a larger study.

Delivery of affordable and equitable cancer care in India.

The delivery of affordable and equitable cancer care is one of India's greatest public health challenges. Public expenditure on cancer in India remains below US$10 per person (compared with more than US$100 per person in high-income countries), and overall public expenditure on health care is still only slightly above 1% of gross domestic product. Out-of-pocket payments, which account for more than three-quarters of cancer expenditures in India, are one of the greatest threats to patients and families, and a cancer diagnosis is increasingly responsible for catastrophic expenditures that negatively affect not only the patient but also the welfare and education of several generations of their family. We explore the complex nature of cancer care systems across India, from state to government levels, and address the crucial issues of infrastructure, manpower shortages, and the pressing need to develop cross-state solutions to prevention and early detection of cancer, in addition to governance of the largely unregulated private sector and the cost of new technologies and drugs. We discuss the role of public insurance schemes, the need to develop new political mandates and authority to set priorities, the necessity to greatly improve the quality of care, and the drive to understand and deliver cost-effective cancer care programmes.

Report of chronic myeloid leukemia in chronic phase from Cancer Institute (Women India Association), Chennai, 2002-2009.

Cancer Institute Chennai is the first Institute of Oncological sciences to be established in the country. In ICON meeting, they presented the data of 516 patients, of which 91% patients achieved complete hematological response. The overall survival was 88% and event free survival was 65% at 5 years.

First report of upfront treatment with Gefitinib in comparison with chemotherapy in advanced non-small cell lung cancer patients from south India: Analysis of 120 patients.

BACKGROUND: Lung cancer is the most common cause of cancer deaths in males and sixth among females in south India. Lung cancer is being increasingly recognized among non-smokers. MATERIALS AND METHODS: Stage IIIB and IV advanced non-small cell lung cancer (NSCLC) patients (n=120) treated from January 2009 to December 2010 were retrospectively analyzed. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. Decision to use upfront Gefitinib was based on parameters like female sex, non-smoking status, adenocarcinoma histology and poor PS. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan Meier method and prognosis by log rank test and Cox regression. RESULTS: BASELINE PARAMETERS: median age: 60 years (22-78 years); male sex: 83 (69.2%); Stage IV: 95(79.2%); adenocarcinoma: 109 (90.8%); smokers: 66 (55%); PS 2/3: 65(54.2%); first-line therapy: Gefitinib: 47 (39.2%), chemotherapy: 73 (60.8%). Among those progressing after chemotherapy, 17 (23%) received second-line Gefitinib. After a median follow-up of 7.5 months (1-26 months), median PFS and OS were 5 months (0-23 months) and 7.5 months (1-26 mo), respectively. On univariate analysis, PFS was significantly improved for non-smokers (7 months vs 4 months, P=0.010), females (7 months vs 5 months, P=0.024) and upfront treatment with Gefitinib (10 months vs 4 months, P=0.014). The only significant factor that affected OS was female sex (18 months vs 9 months, P=0.042). No factors were significant on multivariate analysis. Among PS 2/3 patients, PFS was significantly higher with Gefitinib (n=36) than with single-agent chemotherapy (n=29) [median PFS of 10 months vs 4 months (P=0.017)]. CONCLUSION: In the largest series on the use of first-line Gefitinib from India, we found it to be a useful agent in the treatment of NSCLC, especially in females patients with poor PS and non-smokers, even without Epidermal Growth Factor Receptor (EGFR) mutation testing. Second-line Gefitinib may have negated the OS differences. However, EGFR mutation studies may help in further individualization of therapy.