Brijesh Arora

Prospective Evaluation of Radiotherapy With Concurrent and Adjuvant Temozolomide in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

PURPOSE To present outcome data in a prospective study of radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in children with diffuse intrinsic pontine gliomas (DIPGs). METHODS AND MATERIALS Pediatric patients with newly diagnosed DIPGs were prospectively treated with focal RT to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m(2), Days 1-42). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m(2), Days 1-5) was given every 28 days to a maximum of 12 cycles. Response was evaluated clinically and radiologically with magnetic resonance imaging and positron emission tomography scans. RESULTS Between March 2005 and November 2006, 20 children (mean age, 8.3 years) were accrued. Eighteen patients have died from disease progression, one patient is alive with progressive disease, and one patient is alive with stable disease. Median overall survival and progression-free survival were 9.15 months and 6.9 months, respectively. Grade III/IV toxicity during the concurrent RT-TMZ phase included thrombocytopenia in 3 patients, leucopenia in 2, and vomiting in 7. Transient Grade II skin toxicity developed in the irradiated fields in 18 patients. During the adjuvant TMZ phase, Grade III/IV leucopenia developed in 2 patients and Grade IV thrombocytopenia in 1 patient. Patients with magnetic resonance imaging diagnosis of a high-grade tumor had worse survival than those with a low-grade tumor (p = 0.001). Patients with neurologic improvement after RT-TMZ had significantly better survival than those who did not (p = 0.048). CONCLUSIONS TMZ with RT has not yielded any improvement in the outcome of DIPG compared with RT alone. Further clinical trials should explore novel treatment modalities.

NASOPHARYNGEAL CARCINOMA IN CHILDREN: COMPARISON OF CONVENTIONAL AND INTENSITY-MODULATED RADIOTHERAPY

PURPOSE To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. PATIENTS AND METHODS A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Of the 36 patients, 19 underwent IMRT and 17 underwent CRT. RESULTS After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin (p = 0.006), mucous membrane (p = 0.033), and pharynx (p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio = 5.49, 95% confidence interval, 1.14-26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy (p = 0.001) and 64.4 Gy (p = 0.046) with CRT, respectively. CONCLUSION The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.

Potential Role of Fdg Pet Imaging in Predicting Metastatic Potential and Assessment of Therapeutic Response to Neoadjuvant Chemotherapy in Ewing Sarcoma Family of Tumors

Aims and Objectives: The aim of this study was to retrospectively correlate FDG uptake in primary Ewing sarcoma family of tumors (ESFT) with tumor behavior, and to evaluate whether FDG PET can be used to predict response to neoadjuvant chemotherapy (NACT) in this patient group. Methods: Out of the total 54 patients of recently diagnosed ESFT who underwent pretreatment FDG PET imaging, group I included patients without metastasis at presentation (n = 34) and group II included those with metastasis at presentation (n = 20). Fourteen of these patients had undergone FDG PET after 4 cycles of induction chemotherapy and surgical resection of primary tumor. In this subgroup of 14 patients, maximum standardized uptake value (SUVmax) of primary tumor was estimated before and after 4 cycles of induction chemotherapy and was correlated with the histopathological response in terms of necrosis in the tumor specimen. Results: Mean SUVmax in the primary tumor in group I patients was 6.84 and in group II patients, it was 11.31. The difference between mean SUVmax of these 2 groups was significant by Wilcoxon test analysis, with P < 0.01. In group II patients, SUVmax in metastasis with maximum FDG uptake was consistently lower as compared with that of primary tumor. In subgroup of 14 patients, Pearson correlation analysis showed that percentage change in SUVmax of primary tumor correlated well with percentage necrosis on histopathological examination (P < 0.01). Conclusion: FDG uptake in primary ESFT reflected its metastatic potential and hence the aggressive behavior. The significant correlation between change in metabolic activity of the primary tumor and histopathological response after neoadjuvant chemotherapy suggests that FDG PET may be an ideal noninvasive method to assess tumor behavior and response to therapy in ESFT.

Prognostic Factors and Outcome in Askin-Rosai Tumor: A Review of 104 Patients

PURPOSE To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. METHODS AND MATERIALS Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. RESULTS One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to October 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age ≥18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. CONCLUSION Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.

Orbital medulloepitheliomas—With extensive local invasion and metastasis: A series of three cases with review of literature

Intraocular medulloepithelioma is a rare embryonal neoplasm which usually presents in childhood as a ciliary body mass. This tumor is usually confined to the orbit and rarely tends to be locally aggressive and metastatic. We describe three rare cases of metastatic malignant teratoid medulloepithelioma. The patients were males aged 7, 16 and 25 years with right eye involvement in all the cases. All patients had local recurrence (multiple in two) and metastasis to the intraparotid and cervical lymph nodes. Distinction from round cell tumors and primary salivary gland neoplasms occurring in the parotid gland is strongly warranted, especially in biopsy samples, because the biological behaviour and treatment of medulloepithelioma differs greatly from the above lesions.

A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome TM ) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India

BACKGROUND In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. MATERIALS AND METHODS A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. RESULTS The average body weight of patients was 26.4 ± 14.8 (n=22), 32.9 ± 19.4 (n=23) and 37.9 ± 20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2 ± 13.4, 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8, 16.2 ± 8.3, and 14.7 ± 10.7 days, respectively. The time to resolve fever was 13.3 ± 10.2, 10.9 ± 7.1, 10.1 ± 6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4 ± 9.6, 10.6 ± 7.6 and 7.3 ± 3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS This small randomized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

A Framework for Adapted Nutritional Therapy for Children With Cancer in Low- and Middle-Income Countries: A Report From the SIOP PODC Nutrition Working Group.

The utilization of adapted regimens for the treatment of pediatric malignancies has greatly improved clinical outcomes for children receiving treatment in low‐ and middle‐income countries (LMIC). Nutritional depletion has been associated with poorer outcomes, increased abandonment of therapy, and treatment‐related toxicities. Surveys have found that nutritional intervention is not incorporated routinely into supportive care regimens. Establishing nutritional programs based upon institutional resources may facilitate the incorporation of nutritional therapy into clinical care in a way that is feasible in all settings. We present a framework for establishing and monitoring of nutritional care based on the infrastructure of institutions in LMIC.

Immunophenotypic profile of acute leukemia: Critical analysis and insights gained at a tertiary care center in India

To analyze the spectrum of various types and subtypes of acute leukemia.

An eyelid sialoblastoma-like tumor with a sarcomatoid myoepithelial component.

Nonround cell tumors are rare in children and often difficult to diagnose. This article describes an 18-month-old child who presented with a mass on the outer aspect of the left eyelid. This mass was incompletely excised. Histologically, the tumor had nests of basaloid and relatively round cells with immature acinar or ductular structures similar to those seen in a conventional sialoblastoma, but these nests were embedded in a malignant spindle cell stroma. This stroma on immunohistochemistry was marked with S-100 and cytokeratin, which, in combination with the pertinent ultrastructural evidence, indicated a myoepithelial differentiation. Overall histologic features suggested a tumor similar to a sialoblastoma with sarcomatoid transformation of the myoepithelial component, hitherto not described in literature. This tumor probably arose from the palpebral lobe of the lacrimal gland. Postsurgery, the patient received chemotherapy (6 cycles of ifosfamide, vincristine, and doxorubicin hydrochloride [Adriamycin]) and local radiotherapy in view of residual disease. Three months after completion of the treatment (1 year after surgery), the patient is well, without any local disease. Awareness of this unusual histology of sialoblastoma will help in avoiding misdiagnosis and also refine treatment-related issues on this rare tumor.

Alarming prevalence of community-acquired multidrug-resistant organisms colonization in children with cancer and implications for therapy: A prospective study.

BACKGROUND Infection or colonization with multidrug-resistant organisms (MDRO) is associated with high mortality and morbidity. Knowledge of MDRO colonization may help in planning empirical antibiotic approach in neutropenic patients, which is known to improve patient outcomes. While routine cultures are positive and may help direct antibiotic therapy in only up to 15% neutropenic patients, surveillance cultures are positive in more than 90% of cancer patients. AIMS To assess the rate of MDRO carrier status at presentation and rate of conversion to MDRO during the treatment. MATERIALS AND METHODS Rectal swabs of all the outpatients presenting to pediatric oncology unit were sent within 7 days from date of registration from January 2014 to December 2014. Furthermore, stool cultures/rectal swabs of all patients who got directly admitted to the pediatric ward at presentation were sent within 24 h. Repeat rectal swabs were sent again for patients from this cohort when they got readmitted to the ward at least 15 days after last discharge or when clinically indicated. RESULTS Baseline surveillance rectal swabs were sent for 618 patients, which included 528 children with hematological malignancies and 90 children with solid tumors. Forty-five (7.3%) showed no growth. Of the remaining 573, 197 (34.4%) patients were colonized by two organisms and 30 (5.2%) by three organisms. Three hundred and thirty-four (58.4%) showed extended spectrum beta-lactamase (ESBL) Enterobacteriaceae, of which 165 (49.5%) were ESBL sensitive to beta-lactam with beta-lactamase inhibitors combinations and 169 (50.5%) were resistant to combinations. One hundred and sixteen (20.2%) were carbapenem-resistant Enterobacteriaceae (CRE) and 65 (11.4%) had vancomycin-resistant enterococci in baseline cultures. Only 63 (21%) patients were colonized by a sensitive organism in their baseline surveillance cultures. Morbidity (Intensive Care Unit stay) and mortality was higher in patients colonized by MDR organisms. There was a significant correlation between the place of residence and CRE colonization status with the highest rate (60%) of CRE colonization observed in children from East India. The repeat cultures showed the further conversion of sensitive isolates to MDRO in 80% of these children, of which 40% each converted from non-ESBL and non-CRE to ESBL and CRE, respectively. CONCLUSION This is the first study illustrating the alarming high prevalence of community-acquired MDRO colonization, especially CRE, which has grave implications for therapy for children with cancer potentially compromising delivery of aggressive chemotherapy and affecting outcomes. This incidence further increases during the course of treatment. Knowing the baseline colonization also guides us for the planning of chemotherapy as well as antibiotic approach and infection control strategies. Local antibiotics stewardship including education of the healthcare workers as well as national level interventions to prevent antibiotic misuse in the community is critical to minimize this problem.