Purna Kurkure

Primitive Neuroectodermal Tumor of the Kidney : A Single Institute Series of 16 Patients

OBJECTIVES Primitive neuroectodermal tumor (PNET) of the kidney is a rare entity, the diagnosis usually being made at histopathology. Few cases reported in literature revealed a variable presentation and an aggressive behavior. The purpose of our study was to review our experience in diagnosis and the management of patients with renal PNET. METHODS The records of 16 patients of renal PNET treated between 1995 and 2003 were reviewed retrospectively and our data compared with the literature. RESULTS There were 10 male and 6 female patients with median age of 27 years. At presentation, 10 patients (63%) had localized disease, 5 (31%) had metastatic disease and 1 (6%) had locally advanced disease. The presence of Homer-Wright type rosettes on hematoxylin and eosin staining and CD99 (cluster differentiation) products positivity on immunohistochemistry supported the diagnosis. Radical nephrectomy was performed in operable cases and all patients received chemotherapy. Nine patients received adjuvant radiotherapy to the renal bed. Median follow-up was 31 months (range 4 to 92). Overall median survival was 40 months with 3- and 5-year survival of 60% and 42%, respectively. CONCLUSIONS The diagnosis of renal PNET must be considered in young patients presenting with renal mass. Standard therapy consists of combination of surgical resection, postoperative irradiation and chemotherapy. Chemotherapy regimen used is either RCT II (round cell tumor) protocol or EFT 2001 (Ewings family of tumors) protocol. However, further studies are required to validate the appropriate chemotherapy protocol.

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.

Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial Hospital, Mumbai

PURPOSE To evaluate the disease characteristics and outcome of children with nasopharyngeal carcinoma treated at the Tata Memorial Hospital, Mumbai. METHODS AND MATERIALS Between 1990 and 2000, 81 pediatric patients with a diagnosis of nasopharyngeal carcinoma were treated at the Tata Memorial Hospital. The median age was 14 years. The male/female ratio was 2.8:1. Of the 81 patients, 32 (39%), 21 (26%), and 28 (35%) had T1-T2, T3, and T4 (TNM International Union Against Cancer staging system, 1997), respectively. Ninety-one percent presented with nodal metastasis. Thirty patients (37%) had lymph nodes >6 cm, and 45 (56%) had bilateral nodes at presentation. Histologically, 77 patients (95%) had undifferentiated carcinoma. Eighty-five percent received neoadjuvant multiagent chemotherapy containing bleomycin, methotrexate, and cisplatin, followed by radiotherapy (RT). RESULTS After a median follow-up of 50 months, the disease-free survival (DFS) and overall survival (OS) rate for the entire group was 45% and 54%, respectively. Kaplan-Meier curves were used for evaluation of prognostic factors and were compared using the log-rank test. Nodal status had a significant impact on DFS (p = 0.021) and OS (p = 0.006). Complete responders to chemotherapy had superior DFS (p = 0.000) and OS (p = 0.000). RT doses >60 Gy resulted in better DFS (p = 0.020) and OS (p = 0.012). Combined chemotherapy plus RT resulted in improved DFS (p = 0.457) and OS (p = 0.296), although the difference was not statistically significant. CONCLUSION Combined modality management using chemotherapy and RT resulted in satisfactory locoregional control and OS in pediatric patients with nasopharyngeal carcinoma. Nodal involvement, response to chemotherapy, and RT dose were important prognostic factors.

Desmoplastic small round cell tumor: Extra abdominal and abdominal presentations and the results of treatment

BACKGROUND Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm of adolescent males. Current multimodality treatment prolongs life and rarely achieves cure. AIM To review the presenting features, histopathology and outcome of 18 patients with DSRCT treated at a single institution. SETTING AND DESIGN This is a retrospective observational study of patients with DSRCT who presented at the Tata Memorial Hospital between January 1994 to January 2005. MATERIALS AND METHODS Eighteen patients of DSRCT seen during this period were evaluated for their clinical presentation, response to chemotherapy and other multimodality treatment and overall survival. The cohort of 18 patients included 11 males (61%) and 7 females (39%) with a mean age of 16 years (Range 1(1/2)--30 years). Majority (83%) presented with abdomino-pelvic disease. The others, involving chest wall and extremities. There were 6 patients (33%) with metastatic disease at presentation. RESULTS The treatment primarily included a multimodality approach using a combination of multiagent chemotherapy with adjuvant surgery and radiotherapy as applicable. A response rate of 39% (CR-1, PR-6), with chemotherapy was observed. The overall response rate after multimodality treatment was 39% (CR-5, PR-2). The overall survival was poor except in patients who had complete excision of the tumor. CONCLUSION 0 Abdomino-pelvic site was the commonest presentation, the disease can occur at other non-serosal surfaces also. Despite aggressive treatment the outcome was poor. However, complete surgical excision seems to provide a better survival.

Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas

BACKGROUND Medulloblastoma has recently been found to consist of 4 molecularly and clinically distinct subgroups: WNT, Sonce hedgehog (SHH), Group 3, and Group 4. Deregulated microRNA expression is known to contribute to pathogenesis and has been shown to have diagnostic and prognostic potential in the classification of various cancers. METHODS Molecular subgrouping and microRNA expression analysis of 44 frozen and 59 formalin-fixed paraffin embedded medulloblastomas from an Indian cohort were carried out by real-time RT-PCR assay. RESULTS The differential expression of 9 microRNAs in the 4 molecular subgroups was validated in a set of 101 medulloblastomas. The tumors in the WNT subgroup showed significant (P < .0001) overexpression of miR-193a-3p, miR-224, miR-148a, miR-23b, and miR-365. Reliable classification of medulloblastomas into the 4 molecular subgroups was obtained using a set of 12 protein-coding genes and 9 microRNAs as markers in a real-time RT-PCR assay with an accuracy of 97% as judged by the Prediction Analysis of Microarrays. Age at diagnosis, histology, gender-related incidence, and the relative survival rates of the 4 molecular subgroups in the present Indian cohort were found to be similar to those reported for medulloblastomas from the American and European subcontinent. Non-WNT, non-SHH medulloblastomas underexpressing miR-592 or overexpressing miR-182 were found to have significantly inferior survival rates, indicating utility of these miRNAs as markers for risk stratification. CONCLUSIONS The microRNA based real-time PCR assay is rapid, simple, inexpensive, and useful for molecular classification and risk stratification of medulloblastomas, in particular formalin-fixed paraffin embedded tissues, wherein the expression profile of protein-coding genes is often less reliable due to RNA fragmentation.

Outpatient Antimicrobial Protocol for Febrile Neutropenia: A Nonrandomized Prospective Trial Using Ceftriaxone, Amikacin, and Oral Adjuvant Agents

Broad-spectrum antimicrobial therapy has revolutionized the management of febrile neutropenia (FN) in cancer patients. In vogue is an effective therapy an an outpatient basis. One thousand three hundred episodes of FN observed in 70 pediatric solid tumors (STs) and 65 cases of hematomalignancy (HM) at a median age of 5.5 years were treated with a protocol using once-a-day injectable ceftriaxone plus amikacin and other oral adjuvant antimicrobial agents. The mean duration of FN in the ST group was 4.0 +/- 1.2 days and in the HM group was 5.0 +/- 2.5 days. The mean duration of antimicrobial cover in the ST group was 5.0 +/- 1.75 days and in the HM group was 6.0 +/- 1.5 days. The overall recrudescence rate was 6% and the mean duration to recrudescence was 4 +/- 1.5 days (range 3-6 days). The objectives of this protocol were cost reduction and utilization of the available inpatient resources optimally by reducing the pressures of hospitalization for febrile neutropenia. We concluded that a selected group of patients with FN can be effectively managed with this regimen on an outpatient basis.

Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern

BACKGROUND Up to 10% of patients who develop a nosocomial blood stream infection (BSI) in the hospital have an underlying malignancy. The treatment of infections in patients with malignancy often relies on the use of established guidelines along with the consideration of the local microbiology and antibiotic sensitivity patterns of possible etiologic agents. AIMS This study attempts to identify the likely etiologic agents and the antibiotic sensitivity profile of BSIs in cancer patients. SETTINGS AND DESIGN This was a retrospective study. METHODS AND MATERIAL The study was conducted at a tertiary care center for cancer patients, in which samples representing blood stream infections sent from the Medical Oncology services of the hospital during the year of 2007 were analysed. The microbiological profile and antibiotic sensitivity pattern of these isolates was studied. RESULTS There were 484 isolates that represented BSIs. The most common bacterial isolates from patients with cancer were Pseudomonas spp. (30.37%), Staphylococcus aureus (12.6%) and Acinetobacter spp. (11.57%). Meropenem was the most effective antibiotic with 71.2% sensitivity to the bacterial isolates it was tested against. Oxacillin resistance was seen in 18% of S. aureus isolates. CONCLUSION Gram-negative bacteria were more common as etiologic agents of BSIs in cancer patients. The poor activity of the primary empirical agents for infections in cancer namely ceftazidime and piperacillin-tazobactam is alarming.Strict regulation of vancomycin use should be considered in areas where there is a low prevalence of methicillin-resistant S. aureus (MRSA).

Retinoblastoma: problems and perspectives from India.

This study examined the salient clinical and epidemiological characteristics of retinoblastoma (RB) in India, thereby highlighting the problems encountered there. The epidemiological characteristics of 296 patients with RB over 8 years were evaluated using hospital records and postal follow-ups. Unilateral disease was seen in 61.8% of patients. The overall median age at presentation was 3.5 years (3.5 years for unilateral RB and 1.0 years for bilateral RB). The male/female ratio was 1.4:1. The median duration of symptomatic disease was 8 months. Consanguineous marriage was seen in 17% and family history of RB was noted in 1.7% cases. Also, 2% had a history of other malignancy in the family. Associated congenital malformation was seen in 10.5% of cases. A second malignancy was seen in 0.67% of cases at a mean duration of 4.5 years after completion of therapy. A predominance of advanced-stage disease (74.5% had Reese-Ellsworth group IV and V disease) was seen in our series. Only 43.6% of patients had disease localized to the globe without any infiltration/invasion. The majority of cases had advanced-stage disease at presentation and came from the underprivileged class of society. Patients with bilateral RB presented much earlier than those with unilateral disease. In patients with unilateral RB, higher age at presentation as well as advanced disease may be related to much delay in seeking medical attention. In view of the advanced stage at presentation, there also exist a possibility of difference in the biology of the tumor seen in these patients.

Epidemic iatrogenic Acinetobacter spp. meningitis following administration of intrathecal methotrexate

We report the first outbreak of Acinetobacter species meningitis in a group of children with acute leukaemia following the administration of intrathecal chemotherapy. Eight of twenty patients receiving methotrexate injections on a single day developed signs and symptoms of meningitis within 18 h of treatment, and cases were clustered by time of administration. A cohort study comparing case and non-case patients did not identify any specific host factor associated with meningitis. Acinetobacter calcoaceticus var anitratus was isolated from the cerebrospinal fluid (CSF) of five patients; three patients died. Our investigation determined that the methotrexate was extrinsically contaminated by reused needles, used for reconstitution and administration, which had been inadequately sterilized. Acinetobacter calcoaceticus var anitratus was isolated from an autoclaved needle and a vial of methotrexate used for chemotherapy; these and the clinical isolates had similar antibiograms. After introduction of single-use disposable needles no subsequent cases occurred.