Dynamics of oral human papillomavirus infection in healthy population and head and neck cancer.

The recent increase in high-risk human papillomavirus (HR-HPV)-associated oral and oropharyngeal cancers has gained considerable importance due to their distinct clinical and molecular characteristics. However, the natural history of oral HPV from acquisition to persistence and malignant transformation is still unclear. The global prevalence of oral HPV infection in healthy individuals ranges from 0.67% to 35%, while 31%-38.5% in head and neck cancer (HNC). The persistence rate of oral HR-HPV infection is 5.5% -12.8% globally. India has the highest HNC burden due to apparent differences in predisposing factors compared with the West. The prevalence of oral HPV in healthy individuals and its contribution to HNC is less evident in Indian studies. HR-HPV-associated HNC in this region accounts for 26%, with an active infection in 8%-15% of these tumors. There is a lack of concordance in the expression of p16 as a surrogate marker for HPV detection in HNC because of differences in behavioral risk factors. Due to a lack of evidence, treatment de-escalation cannot be implemented despite the improved outcome of HPV-associated oropharyngeal cancers. This review critically analyzes the existing literature on the dynamics of oral HPV infection and HPV-associated HNC, identifying potential avenues for future research. A better understanding of the oncogenic role of HR-HPV in HNC will help to formulate novel therapeutic approaches and is expected to have a significant public health impact as preventive strategies can be implemented.

Phosphoproteome of signaling by ErbB2 in ovarian cancer cells.

The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals are transduced through ErbB2 are well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 in ovarian cancer cells. The ErbB2 specific proteins identified in SKOV-3 cells were Myristoylated alanine-rich C-kinase substrate, Protein capicua homolog, Protein peptidyl isomerase G, Protein PRRC2C, Chromobox homolog1 and PRP4 homolog. We have evaluated three phosphoproteins PKM2, Aldose reductase and MARCKS in SKOV-3 cells. We observed that PKM2 was phosphorylated by EGF but was not inhibited by Lapatinib and CP724714. The activity of aldose reductase in reducing NADPH as a substrate was significantly higher in EGF stimulated cells which was inhibited by Lapatinib and CP724714 but not by Geftinib (EGFR inhibitor). MARCKS was phosphorylated on stimulation of SKOV-3 cells with EGF that was inhibited by Lapatinib and CP724714 which was dependent on the kinase activity of ErbB2. These results have identified phosphoproteins that are specific to ErbB2 which have not been previously reported and sets the basis for future experiments.

Development and in vitro characterisation of an induced pluripotent stem cell model of ovarian cancer.

Ovarian cancer recurs despite advances in treatment and is due to drug resistance. The persistence of cancer stem cells (CSCs) is one of the causes. It has been challenging to maintain CSCs long term in culture from primary malignant cells. Reprogramming cancer cells into induced pluripotent stem cells (iPSCs) could be an approach to achieve this. An ovarian cancer cell line, PEO4, was initially reprogrammed into iPSCs using the classical four factors OCT4, SOX2, KLF4 and MYC (OSKM) using lentivirus transduction. The PEO4-OSKM-cells had all the hallmarks of iPSCs. As MYC is oncogenic, we have replaced it with GLIS1 and show that PEO4 cells could be transformed into iPSCs. The transfection efficiency was two-fold better with OCT4-SOX2-KLF4-GLIS1 (OSKG) with larger colonies. Further, normal fallopian tube epithelial cells were also transformed using OSKG into iPSCs. iPSCs expressed CSCs markers such as CD133, EPHA1, ALDH1A1 and LGR5 prominently and were more resistant to cisplatin and taxol as compared to parental PEO4 cells. PEO4-OSKM-iPSCs cells formed more colonies in a clonogenic assay as compared to PEO4-OSKG-iPSCs and parental cells. These results provide a first insight that both an ovarian cancer cell line and fallopian tube epithelial cells can be reprogrammed and GLIS1 can successfully replace MYC as a transcription factor. This in vitro model is useful for future experiments to understand the characteristics of CSCs in the pathogenesis of ovarian cancer.

"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.

Induced pluripotent stem cells: A new strategy to model human cancer.

Induced pluripotent stem cells are derived from adult somatic cells by ectopic expression of stem cell factors OCT4, SOX2, MYC and KLF4. These cells have characteristic features similar to embryonic stem cells. Although there exists in vitro and in vivo models of cancer, recapitulating the earliest events in the pathogenesis remain challenging. More recently, induced pluripotent stem cells have been generated to model human disease and cancer. There are advantages in the cancer models derived from these cells as compared to existing conventional approaches. Induced pluripotent stem cells have been generated from cancer cell lines, primary tumours and from those with an inherited predisposition to develop cancer. In addition, these cells provide a valuable tool in understanding the pathogenesis of familial cancer in its earliest stages, and to identify additional genetic alterations that are required to develop cancer. Furthermore, these cells can serve as a resource in drug screening and developing new therapies.

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.

A systematic understanding of signaling by ErbB2 in cancer using phosphoproteomics.

ErbB2 is an important receptor tyrosine kinase and a member of the ErbB family. Although it does not have a specific ligand, it transmits signals downstream by heterodimerization with other receptors in the family. It plays a major role in a variety of cellular responses like proliferation, differentiation, and adhesion. ErbB2 is amplified at the DNA level in breast cancer (20%-30%) and gastric cancer (10%-20%), and trastuzumab is effective as a therapeutic antibody. This review is a critical analysis of the currently published data on the signaling pathways of ErbB2 and the interacting proteins. It also focuses on the techniques that are currently available to evaluate the entire phosphoproteome following activation of ErbB2. Identification of new and relevant phosphoproteins can not only serve as new therapeutic targets but also as a surrogate marker in patients to assess the activity of compounds that inhibit ErbB2. Overall, such analysis will improve understanding of signaling by ErbB2.

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.

Short-course lenalidomide plus low-dose dexamethasone in the treatment of newly diagnosed multiple myeloma-a single-centre pragmatic study.

PURPOSE: We assessed response to treatment, toxicity, time to progression, progression-free survival, and overall survival in patients newly diagnosed with multiple myeloma who were ineligible for or unwilling to undergo transplantation and who were treated with a combination of lenalidomide and low-dose dexamethasone for a fixed 6 cycles in a resource-constrained environment. METHODS: This pragmatic study, conducted in a single tertiary cancer centre in South India, enrolled patients from May 2009 till April 2011. Treatment included lenalidomide 25 mg daily for 21 days, with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle, for 6 cycles. Response was evaluated after the 3rd and 6th cycles of treatment. All patients were followed for 5 years. RESULTS: The study enrolled 51 patients. Median age in the group was 61 years (range: 38-76 years). Immunoglobulin G or A myeloma constituted 70.6% of the diagnoses, and light-chain myeloma constituted 29.4%. Stages i, ii, and iii (International Staging System) disease constituted 21.4%, 28.6%, and 50% of the diagnoses respectively. All patients were transplantation-eligible, but 34 (66.7%) refused for economic reasons. After treatment, 19.6% of the patients achieved a stringent complete response; 35.3%, a complete response; 5.9%, a very good partial response; and 29.4%, a partial response, for an overall response rate of 90.2%. Stable disease was seen in 3.9% of patients, and progressive disease, in 5.9%. Grade 3 or greater nonhematologic and hematologic toxicity occurred in 35.2% and 11.7% of patients respectively. Pulmonary embolism occurred in 1 patient. No patient experienced deep-vein thrombosis or peripheral neuropathy. The median follow-up duration was 66 months. All patients experienced disease progression. Median progression-free survival was 16 months. In 10 patients, re-challenge with lenalidomide and dexamethasone achieved a second complete response. At the time of writing, 19 patients had died. The overall survival rate at 5 years was 62.74%. Median overall survival is not yet reached. CONCLUSIONS: In a resource-constrained setting, lenalidomide with low-dose dexamethasone is an effective treatment with acceptable toxicity in patients newly diagnosed with multiple myeloma and not planned for transplantation. Complete responses were significantly more frequent than reported in the Western literature. Occurrence of clinical deep-vein thrombosis was rare, but hyperglycemia was common. An abbreviated course of treatment is suboptimal in multiple myeloma. Maintenance regimens should be advocated.

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.

Expression of a novel endothelial marker, C-type lectin 14A, in epithelial ovarian cancer and its prognostic significance.

OBJECTIVE: The purpose of this study was to evaluate microvessel density (MVD) as assessed by C-type lectin 14A (CLEC14A), which is a new marker for endothelial cells, and compare its expression to CD31 and CD105 in epithelial ovarian cancer (EOC). METHODS: MVD was evaluated in tumors (n = 50) from patients with EOC who underwent primary surgery and in patients with EOC who received preoperative chemotherapy (n = 49) using immunohistochemistry with antibodies to CLEC14A, CD31 and CD105. The median duration of follow-up was 24.5 months (range 1-101 months). The effect of prognostic factors on event-free survival (EFS) and overall survival (OS) was assessed using the Cox regression model. RESULTS: The amount of residual disease was found to be an independent prognostic factor in multivariate analysis with respect to EFS (P = 0.009) and OS (P < 0.001). The mean MVD of CLEC14A (MVD = 6), in tumors from patients who underwent primary surgery, was significantly lower than that of CD31 (MVD = 25, P < 0.0001) and CD105 (MVD = 11, P = 0.018). However, there was no significant correlation between MVD as detected by these markers and clinical outcome. There was no expression of CLEC14A in tumors from patients who received preoperative chemotherapy and the MVD of CD31 and CD105 was significantly reduced (P = 0.001 and 0.006, respectively) in this set of patients. CONCLUSION: This study demonstrates MVD as detected by CLEC14A in EOC. Treatment with chemotherapy reduces tumor blood vessels significantly. We suggest that CLEC14A may be a more specific endothelial marker to assess tumor angiogenesis.

Lymphoblastic lymphoma presenting as bilateral renal enlargement diagnosed by percutaneous kidney biopsy: Report of three cases.

Renal involvement by lymphoma can be a diagnostic challenge. Acute kidney injury (AKI) is an unusual manifestation of lymphomatous infiltration in the kidneys. We report three cases of lymphoblastic lymphoma, a very rare form of lymphoma, presenting with AKI and bilateral enlargement of kidneys, diagnosed by percutaneous kidney biopsy. Lymphomatous infiltration should be suspected with such clinical presentation. Kidney biopsy is a valuable diagnostic tool, to establish the correct diagnosis and subtype of lymphoma for timely initiation of therapy for these aggressive hematological malignancies.

Tumour angiogenesis-Origin of blood vessels.

The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments. It is now evident that tumours arise from a small population of cells called cancer stem cells (CSCs) or tumour initiating cells. Recent data suggest that a proportion of tumour endothelial cells arise from cancer stem cells in glioblastoma. This was demonstrated both in vitro and in vivo. The analysis of chromosomal abnormalities in endothelial cells showed identical genetic changes to those identified in tumour cells. However, another report contradicted these results from the earlier studies in glioblastoma and had shown that CSCs give rise to pericytes and not endothelial cells. The main thrust of this review is the critical analysis of the conflicting data from different studies and the remaining questions in this field of research. The mechanism by which this phenomenon occurs is also discussed in detail. The transdifferentiation of CSCs to endothelial cells/pericytes has many implications in the progression and metastasis of the tumours and hence it would be a novel target for antiangiogenic therapy.

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).

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.