Venkatraman Radhakrishnan

Prognostic markers in osteosarcoma

Osteosarcoma is the most common bone tumor seen in the pediatric and adolescent age group. Survival rates in osteosarcoma have improved considerably from 20 to 65% since the 1980s with the advent of multiagent chemotherapy. Further improvement in survival has not been achieved owing to lack of well-validated prognostic markers and better therapeutic agents. Markers involved with angiogenesis, cell adhesion, apoptosis and cell cycle have been shown recently to play an important role in osteosarcoma growth, differentiation and metastasis. Over the coming years, the new molecular markers may be able not only to prognosticate osteosarcoma patients at baseline but also to serve as therapeutic targets and thereby improve survival rates further. Noninvasive imaging methods in osteosarcoma such as PET-CT and dynamic contrast enhanced and diffusion-weighted MRI hold a lot of promise as surrogate methods for prognostication and response assessment.

Pediatric Nonlymphoblastic Non-Hodgkin Lymphoma: Baseline, Interim, and Posttreatment PET/CT versus Contrast-enhanced CT for Evaluation—A Prospective Study

PURPOSE To prospectively examine the roles of positron emission tomography (PET)/computed tomography (CT) and conventional contrast material-enhanced CT at baseline, after two cycles of chemotherapy, and after completion of chemotherapy in pediatric patients with nonlymphoblastic non-Hodgkin lymphoma (NHL) who were treated with similar standard treatment protocols. MATERIALS AND METHODS The institutional ethics committee approved the study protocol, and all patients were enrolled after written informed consent was obtained. Patients with nonlymphoblastic NHL were prospectively enrolled between January 2008 and March 2010. Patients underwent contrast-enhanced CT and PET/CT for staging and for response assessment after two cycles of chemotherapy (interim) and treatment completion. Complete metabolic response versus no metabolic response at PET/CT and complete response versus no complete response at contrast-enhanced CT was analyzed by using Kaplan-Meier survival analysis. RESULTS The final study included 34 patients with nonlymphoblastic NHL (median age, 10.5 years). Baseline PET/CT and contrast-enhanced CT showed concordance in depiction of 112 disease sites; PET/CT depicted 18 more disease sites and two fewer disease sites than contrast-enhanced CT (P = .0003). Disease in five of 34 patients was upstaged, and disease in no patient was downstaged at PET/CT. There was 100% (four of four) concordance between bone marrow involvement at biopsy and stage at PET/CT. The median length of follow-up was 20.3 months. Response at interim PET/CT and contrast-enhanced CT could not predict progression-free survival (PFS) (P = .083 and .18, respectively) or overall survival (OS) (P = .159 and.08, respectively). Posttreatment PET/CT and contrast-enhanced CT findings could predict PFS (P = .036 and .002, respectively) and posttreatment contrast-enhanced CT findings could predict OS (P = .035); however, posttreatment PET/CT findings could not predict OS (P = .067). CONCLUSION PET/CT depicts additional sites compared with contrast-enhanced CT and results in upstaging of disease. Either PET/CT or contrast-enhanced CT may be used for response assessment and prognostication in stage III or IV nonlymphoblastic pediatric NHL.

Current therapy and recent advances in the management of retinoblastoma.

Retinoblastoma is the most common intraocular malignancy in children. The survival of retinoblastoma patients and visual outcome has improved dramatically in the developed world. This can be attributed to early tumor recognition and advances in the management of retinoblastoma. Chemoreduction followed by adjuvant consolidative treatment has replaced external beam radiotherapy as the primary modality of treatment for intraocular retinoblastoma. Further, histopathological high-risk factors have been identified in enucleated eyes, allowing use of prophylactic chemotherapy to take care of possible micrometastasis. The survival in case of extraocular retinoblastoma is still low, and the reported survival rate ranges between 50% and 70%. In developing countries, the overall survival of retinoblastoma patients remains low, primarily due to a delayed presentation, resulting in larger proportions of extraocular disease compared with the developed world, where majority of the disease is intraocular. Greater efforts need to be directed toward early tumor recognition in order to improve the survival of retinoblastoma patients in the developing world. In this article, we provide an overview of the current clinical management of retinoblastoma.

Gastric cancer in India.

The incidence of gastric cancer in India is low compared to developed countries, though there are certain geographical areas (Southern part and northeastern states of country) where the incidence is comparable to high-incidence areas of world. Despite the large number of patients being treated for gastric cancer, there are not sufficient publications discussing associated risk factors and outcomes in these patients. This article discusses relevant Indian epidemiological and clinical studies about gastric cancers. This article also highlights the gap in publication from India and developed countries regarding gastric cancer and stresses on collaborative efforts of the Indian scientific community to conduct epidemiological, pathological, and clinical studies to have a new standard of care for Indian patients.

Nonequilibrium phenomena in plasmas

Preface.- Section 1: Space Plasmas.- Nonequilibrium Phenomena in the Earths Magnetosphere: Phase Transition, Self-organized Criticality and Turbulence A.S. Sharma, D.N. Baker and J. Borovsky. Complexity and Intermittent Turbulence in Space Plasmas T. Chang, S.W.Y. Tam and C.C. Wu. Complexity and Topological Disorder in the Earths Magnetotail Dynamics G. Consolini, T. Chang and A.T.Y. Lui. Simulation Study of SOC Dynamics in Driven Current Sheet Models J. Klimas, V.M. Uritsky, D. Vassiliadis and D.N. Baker. Two State Transition Model of the Magnetosphere T. Tanaka. Global and Multiscale Phenomena of the Magnetosphere A.S. Sharma, A.Y. Ukhorskiy and M.I. Sitnov. Low-Frequency Magnetic Fluctuations in the Plasma Sheet A. Petrukovich. Magnetospheric Multiscale Mission: Cross-scale Exploration of Complexity in the Magnetosphere A.S. Sharma and S.A. Curtis. Section 2: Laboratory Plasmas.- Perspectives of Intermittency in the Edge Turbulence of Fusion Devices R. Jha, P.K. Kaw and A. Das. Transition to Self-organized High Confinement States in Tokamak Plasmas: Transition to H-mode in Tokamak Plasmas P.N. Guzdar, R.G. Kleva, R.J. Groebner and P. Gohil. Internal Transport Barriors in Magnetized Plasmas X. Garbet, P. Ghendrih, Y. Sarazin, P. Beyer, C. Figarella and S. Benkadda. Characterization of Turbulence in terms of Probability Density Function: A New Approach to Describe Transport in Fusion Plasmas C. Hidalgo, B. Goncalves and M.A. Pedrosa. Phase Transition in Dusty Plasmas G. Ganguli, G. Joyce and M. Lampe. Section 3: Cross-disciplinary Studies.- Precursors of Catastrophic Failures S. Pradhan and B.K. Chakrabarti. Multiscale Interactions and Predictability of the Indian Summer Monsoon B.N. Goswami and R.S. Ajaya Mohan

Role of PET/CT in Staging and Evaluation of Treatment Response After 3 Cycles of Chemotherapy in Locally Advanced Retinoblastoma: A Prospective Study

The present study prospectively evaluated the role of 18F-FDG PET/CT for staging, neoadjuvant chemotherapy response evaluation, and final outcome assessment in International Retinoblastoma Staging System (IRSS) stage III retinoblastoma. Methods: Twenty-five consecutive IRSS stage III patients, with a median age of 3 y, were prospectively enrolled after ethics approval. All patients received neoadjuvant chemotherapy followed by enucleation, radiotherapy, and adjuvant chemotherapy. PET/CT was performed at baseline (PET/CT-1) and after 3 cycles of neoadjuvant chemotherapy (PET/CT-2). All 25 patients underwent PET/CT-1, and 21 of 25 patients underwent PET/CT-2. PET/CT-1 was compared with routine staging, and response on PET/CT-2 was assessed by criteria from the European Organization for Research and Treatment of Cancer response. Event-free survival (EFS) and overall survival (OS) were calculated using Kaplan–Meier survival analysis, and differences between the groups were compared using log-rank test. A P value of 0.05 or less was considered significant. Results: Increased 18F-FDG uptake was noted in primary extraocular tumor in all patients, except 5 with bilateral retinoblastoma (one eye with advanced and the other eye with intraocular disease) in whom the intraocular tumor did not show 18F-FDG uptake. Five of 22 IRSS stage IIIA patients with clinically negative cervical lymph node involvement were found to have uptake in cervical lymph nodes on PET/CT-1, and 2 of 3 IRSS stage IIIB patients with pathologically confirmed cervical lymph node involvement did not show any uptake in the involved lymph nodes. No significant difference in EFS and OS was seen between IRSS stage IIIA and IIIB patients using routine staging or PET/CT staging (P ≥ 0.05); however, there was a trend toward better OS in patients with IRSS stage IIIB disease on PET/CT (P = 0.065). There was no significant discordance between routine staging and PET/CT staging (P = 0.256). The 8 patients with optic nerve uptake had lower EFS (P = 0.0001) and OS (P = 0.0009) than did 17 patients without optic nerve uptake on PET/CT-1. The 17 patients with complete response or partial response had better EFS (P = 0.042) and OS (P = 0.026) than did the 4 patients with progressive disease on PET/CT-2. Conclusion: Optic nerve uptake at baseline on PET/CT and response after neoadjuvant chemotherapy according to criteria from the European Organization for Research and Treatment of Cancer are strong predictors of EFS and OS in IRSS stage III retinoblastoma.

MRI findings at baseline and after neoadjuvant chemotherapy in orbital retinoblastoma (IRSS stage III)

Background Published findings on MRI results in retinoblastoma patients treated with neoadjuvant chemotherapy (NACT) are lacking. The present study evaluates the role of MRI in International Retinoblastoma Staging System (IRSS) stage III retinoblastoma treated with NACT. Methods 28 consecutive IRSS stage III retinoblastoma patients underwent MRI at baseline and after three cycles of NACT prior to enucleation. MRI films were reviewed retrospectively by an ophthalmic radiologist who was masked to patient outcome. Optic nerves were staged based on their thickness, contrast enhancement and length of involvement on MRI. Response evaluation criteria were based on optic nerve staging and changes in the size of the orbital mass on MRI after NACT. Results The proposed staging at baseline and after NACT was able to predict event-free-survival (EFS) (p=0.005 and p <0.001, respectively) and overall survival (OS) (p=0.002 and p=0.001, respectively) using the log-rank test for trends. Patients with complete or partial response according to the proposed response evaluation criteria had significantly better EFS (p<0.001) and OS (p=0.024) than those who had stable or progressive disease. Conclusions The proposed MRI based optic nerve staging system and response evaluation criteria were able to predict EFS and OS at baseline and after NACT.

Nasopharyngeal carcinoma with splenic and cystic liver metastases in a pediatric patient: 18F-FDG PET-CT findings

Pediatric nasopharyngeal carcinoma (NPC) is rare and usually poorly differentiated. We report a 14-year-old boy with NPC with metastases to liver, spleen, lymph nodes and bone marrow. The liver metastases closely resembled benign cystic liver disease on imaging; however, they showed intense uptake similar to other metastatic sites on positron emission tomography (PET) scan. A liver biopsy could not be performed on the boy. The boy responded clinically to platinum-based chemotherapy, and all the baseline PET-positive lesions became negative. This case highlights the rarity of splenic and cystic liver metastases in pediatric NPC and demonstrates the potential use of PET/CT in diagnosis, staging and response assessment in metastatic pediatric NPC.

Diagnosis and Management of Rhabdomyosarcoma in Children and Adolescents: ICMR Consensus Document

Rhabdomyosarcoma (RMS) is a highly malignant tumor which is thought to originate from the pluripotent mesenchyme. It is the most common soft-tissue sarcoma of childhood. This review article summarizes the recent and older published literature and gives an overview of management of RMS in children. RMS can arise in a wide variety of primary sites, some of which are associated with specific patterns of local invasion, regional lymph nodal spread, therapeutic response and long term outcome, hence requiring physicians to be familiar with site-specific staging and treatment details. Most common primary sites include the head and neck region, genitourinary tract, and extremities. Prognosis for children and adolescents with RMS has recently improved substantially, especially for patients with local or locally extensive disease because of the development of multi-modal therapy incorporating surgery, dose-intensive combination chemotherapy, and radiation therapy. Despite aggressive approaches the outcome for patients who present with metastatic disease remains unsatisfactory. Clinical trials are ongoing to reduce toxicity and improve outcomes of such patients; newer agents in combination are being investigated.

Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia

Background: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal infections (IFIs) during induction therapy of acute myeloid leukemia (AML). Posaconazole is considered the standard of care. Voriconazole, a generic cheaper alternative is a newer generation azole with broad anti-fungal activity. There is limited data on the use of voriconazole as a prophylactic drug. Materials and Methods: A single-center, prospective study was performed during which patients with AML undergoing induction chemotherapy received voriconazole as AFP (April 2012 to February 2014). Outcomes were compared with historical patients who received fluconazole as AFP (January 2011-March 2012, n = 66). Results: Seventy-five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1) received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with respect to baseline characteristics. Voriconazole (when compared to fluconazole) reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P < 0.001) and delayed the start of therapeutic antifungals in those who needed it (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not significant. Three patients discontinued voriconazole due to side-effects. Conclusion: Voriconazole is an effective and safe oral agent for IFI prophylaxis during induction therapy of AML. Availability of generic equivalents makes this a more economical alternative to posaconazole.