Impact of Surgical Timing (Primary, Delayed, or Second Look) on Surgical Morbidity and Outcomes in Malignant Germ Cell Tumor of the Ovary in Children.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCT) are rare in children. Surgery with or without chemotherapy is the primary treatment approach. This study aimed to analyze the impact of primary and delayed surgery on surgical morbidity and outcomes. Second-look surgery after inadequate surgical staging and the various components of surgical staging were also evaluated. METHODS: Children below 15 years with MOGCT treated between 2006 and 2022 were analyzed. A comparison of patients undergoing primary, delayed, and second-look surgery was performed. RESULTS: 118 patients with a median age of 12 (0.11-15) years were eligible. Forty patients underwent primary, 51 delayed, and 27 second-look surgeries. Overall complications, including tumor rupture, blood loss, and adjacent organ removal, were significantly higher in the primary compared to the delayed surgery group (p = 0.0001). Second-look surgery conceded more blood loss (p = 0.0001), extended duration (p = 0.03), and complications (p = 0.004) than delayed surgery. The compliance with surgical guidelines was 100% for most components, with a positive yield rate of 10-80%. At a median follow-up of 5.2 years, the 5-year event-free survival (EFS) and overall survival (OS) for the entire cohort are 86% and 89%, respectively. The OS and EFS did not differ by the timing of surgery, although the second-look surgery demonstrated relatively inferior outcomes consequential to initial suboptimal surgery. CONCLUSIONS: MOGCT shows favorable outcomes. Delayed surgery after chemotherapy in appropriately selected patients minimizes the morbidity of surgery with similar outcomes compared to primary surgery. An optimal initial surgery is essential since second-look surgery produces significant morbidity. Prognosis Study, Level II evidence.

Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center.

BACKGROUND AND AIMS: Data on the outcome and prognostic indicators in extracranial relapsed/refractory germ cell tumors (rel/ref-GCTs) in children are limited to a few studies. This study looks at remission rates and outcomes of rel/ref-GCTs treated with conventional salvage chemotherapy (SC) regimens without stem cell rescue at a single center in the developing world. METHODS: Patients treated at our center from January 2009 to December 2018 were included. Risk at primary presentation was stratified as all completely excised teratomas and stage I gonadal tumors being low risk (LR); stage IV ovarian, stage III-IV extragonadal GCTs as high risk (HR), and the remaining as intermediate risk (IR). SC regimens were: vinblastine-ifosfamide-cisplatin/carboplatin or paclitaxel-ifosfamide-cisplatin/carboplatin, or cisplatin/carboplatin-etoposide-bleomycin. Local therapy was either surgery and/or radiotherapy. RESULTS: The analyzable cohort comprised 50 patients (44 = rel-GCTs; 6 = ref-GCTs) with a median age of 3.8 years and male:female ratio of 1.27:1. Primary location was ovary in 16 (32%), testicular in 10 (20%), and extragonadal in the rest (48%). Local, metastatic, and combined progression was noted in 28 (56%), 14 (28%), and eight (16%) patients, respectively, at a median time of 8.5 months. At a median follow-up of 60 months, the 5-year event-free survival (EFS) and overall survival (OS) of the entire cohort (n = 50) were 42.4% and 50.0%, respectively. In patients previously exposed to platinum analogs (n = 38), 5-year-EFS and OS were 27.7% and 31.7%, respectively. Local relapses did better when compared to metastatic and combined relapses (5-year EFS: 64% vs. 23% vs. 0%; p = .009). LR and IR tumors did better compared to HR (5-year EFS: 81.5% vs. 49.3% vs. 6.5%; p = .002). Patients with normalization of tumor markers after two cycles had a superior EFS (57.6% vs. 0%; p < .001). Relapsed tumors fared better than primary refractory GCTs (5-year EFS: 48.6% vs. 0%; p < .001). CONCLUSIONS: Primary refractory GCTs, extragonadal rel-GCTs, and rel/ref-GCTs with a poor biochemical response did poorly with conventional SC and need alternative treatment strategies. The rel/ref-testicular GCTs had the best chance of salvage despite a second recurrence (5-year EFS and OS: 28.60% and 42.90%, respectively).

Pediatric cancer-associated thrombosis: Analysis from a tertiary care cancer center in India.

BACKGROUND AND AIMS: Thrombotic events (TEs) have been extensively studied in adult cancer patients, but data in children are limited. We prospectively analyzed pediatric cancer-associated thrombosis (PCAT) in children with malignancies. METHODS: Children below 15 years of age with confirmed malignancies, treated at a large tertiary cancer center in India from July 2015 to March 2020 developing any TE were eligible. A standardized approach for detection and management was followed. Data were collected after informed consent. RESULTS: Of 6132 eligible children, 150 (2.44%) had 152 TEs, with median age 8.5 years and male:female of 1.83:1. Most TEs occurred on chemotherapy: 111 (74.0%). The most common site was central nervous system (CNS) 59 (39.3%), followed by upper-limb venous system 37 (24.7%). Hemato-lymphoid (HL) malignancies were more prone to PCAT than solid tumors (ST) (incidence 3.23% vs. 1.58%; odds ratio [OR] = 2.06, 95% confidence interval [CI] [1.36-2.88]; p < .001). Malignancies associated with PCAT were acute lymphoblastic leukemia (ALL) 2.94%, acute myeloid leukemia (AML) 6.66%, and non-Hodgkin lymphomas 5.35%. Response imaging done in 106 (70.7%) children showed complete to partial resolution in almost 90% children. Death was attributable to TE in seven (4.66%) children. Age above 10 years (OR 2.33, 95% CI [1.59-3.41]; p < .001), AML (OR 4.62, 95% CI [1.98-10.74]; p = .0062), and non-Hodgkin lymphoma (OR 4.01, 95% CI [1.15-14.04]; p = .029) were significantly associated with TEs. In ALL, age more than 10 years (OR 1.86, 95% CI [1.06-3.24]; p < .03), T-ALL (OR 3.32, 95% CI [1.69-6.54]; p = .001), and intermediate-risk group (OR 4.97, 95% CI [1.12-22.02]; p = .035) were significantly associated with thrombosis. The 2-year event-free survival (EFS) for HL malignancies with PCAT was 55.3% versus 72.1% in those without PCAT (p = .05), overall survival (OS) being 84.6% versus 80.0% (p = .32). CONCLUSION: Incidence of PCAT was 2.4%, and occurred predominantly in older children with hematolymphoid malignancies early in treatment. Most resolved completely with low molecular weight heparin (LMWH) and mortality was low. In hematolymphoid malignancies, PCAT reduce EFS, highlighting the need for prevention.

Can 18 F-FDG-Positron Emission Tomography be a Prognostic Tool in Children With Rhabdomyosarcoma Treated With Definitive Radiotherapy?

BACKGROUND: Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18 F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS. MATERIALS AND METHODS: Children 15 years old or below with Group III/IV RMS who received only definitive radiotherapy for local control from June 2013 to December 2018, and had 18 F-FDG-PET CT at 3 months post-RT were retrospectively analyzed for outcomes and other prognostic factors. RESULTS: Sixty-three children were eligible (Group III-55, Group IV-8). 18 F-FDG-PET CT scan done 3 months postradiotherapy showed FDG-avid residual masses in 10 patients (15.9%), anatomic residual in 24 (38.1%), and no anatomic/FDG-avid residual in 29(46.0%). At a median follow-up of 38 months (interquartile range, 24 to 55 mo), 3-year EFS of patients with FDG-avid residual masses was 40.0% (95% CI: 18.7% to 85.5%) versus the rest of the cohort, which was 71.9% (95% CI: 59.8% to 86.5%) ( P =0.008). Three-year OS of patients with FDG-avid residual masses was 50.8% (95% CI: 25.7% to 100.0%) versus the rest of the cohort, which was 77.0% (95% CI: 65.1% to 91.0%) ( P =0.037). Presence of FDG-avid residual disease persisting post-RT affected both EFS [HR-3.34 (95% CI: 1.29 to 8.68) ( P =0.013)] and OS [HR-3.20 (95% CI: 1.01 to 10.12) ( P =0.048)] on univariate analysis and this significance was retained for EFS in multivariate analysis [HR-3.52 (95% CI: 1.33 to 9.30) ( P =0.011)]. CONCLUSIONS: Persistent metabolic activity in residual disease post-chemoradiotherapy in RMS may portend a poorer prognosis with an increased risk of relapse. This subset of high-risk patients needs to be identified, and further trials are warranted to develop strategies to improve their outcomes.

Clinical features, predictors and outcome of posterior reversible encephalopathy syndrome (PRES) in children with hematolymphoid malignancies.

BACKGROUND AND AIM: Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome characterized by a neurotoxic state with vasogenic edema. We studied the clinical profile, predisposing factors, imaging features, and outcome of PRES in children receiving treatment for hematolymphoid malignancies. METHODS: Retrospective analysis of the clinical data and radiological features of patients with PRES diagnosed between June 2014 and December 2019. RESULTS: Fifty-two patients (boy: girl = 3:1) were diagnosed with PRES during the study period with a median age of 11 (range:1-15) years. Primary diagnoses were acute leukemias (n = 42), non-Hodgkin lymphoma (n = 8), Hodgkin lymphoma (n = 1), and Langerhan's cell histiocytosis (n = 1). Most common presenting symptoms were seizures (n = 52), altered sensorium (n = 42), headache (n = 39), and visual disturbances (n = 8). Hypertension at time of diagnosis was noted in 50 (96%) patients. Classic hyper-intense lesions on FLAIR and diffusion weighed (DW) images were noted in parieto-occipital region in 39 patients (75%). Central PRES involving basal ganglia was seen in 3 (6%) patients. A subsequent neuro-imaging was done in 18 patients (MRI: 13; CT: 5) at a median interval of 16.2 weeks. Neurological sequelae were observed in 10 (19%) patients, whereas 1 succumbed due to PRES. CONCLUSIONS: PRES is an important clinico-radiological syndrome in patients undergoing chemotherapy for hematological malignancies. High index of suspicion, early diffusion-weighted images on MRI in children with classic symptoms help in early diagnosis. A small minority of patients may develop long-term sequelae.

Outcomes and prognostic variables of extracranial germ cell tumors in children and adolescents treated over a decade: A developing world perspective.

BACKGROUND: The purpose of this single-center study was to analyze the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multimodality regimen. METHODS: Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January 2009 to December 2018) treated on a uniform institution-based protocol consisting of both cisplatin- and carboplatin-based regimens. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk [LR]); stage IV ovarian, stage III-IV extragonadal GCTs received six cycles of chemotherapy (high risk [HR]), and the remaining received four cycles of chemotherapy (intermediate risk [IR]). RESULTS: A total of 297 children were treated with a female:male ratio of 1.72:1 and median age of 4 years. Forty-three children had pure teratomas. Gonadal GCTs (N = 180) were more common than extragonadal GCTs (N = 117) with ovary as primary site in 128 children (43%) and sacrococcygeal site being the commonest extragonadal location (N = 41; 14%). LR, IR, and HR disease were noted in 60 (20.2%), 125 (42%), and 112 (37.8%) patients, respectively. Three-fourths of ovarian tumors and half of testicular tumors operated prior to presentation needed upstaging. Forty-one patients relapsed and 43 children expired (disease-related: 33; toxic deaths: 9; unknown: 1). The 5-year event-free survival (EFS)/overall survival (OS) of malignant GCT (n = 254) was 72.50%/82.70%, respectively, with gonadal site (p = .001), LR and IR (p = .001) and nonmetastatic disease (p = .001) being favorable prognostic variables. CONCLUSIONS: The LR and IR GCTs in our cohort had an excellent outcome. A significant proportion of IR gonadal GCTs can be spared of systemic chemotherapy by adhering to strict surgical guidelines. In HR GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity, more so in a resource-limited setting.

Clinical outcomes and prognostic factors in children with B-cell lymphoblastic lymphoma (LBL) treated according to on modified BFM-90 protocol: Experience from a Tertiary cancer care center in India.

Pediatric B-cell lymphoblastic lymphoma (LBL) is a rare entity, and appropriate treatment for pediatric B-cell LBL is not well defined. While intensive ALL type regimens achieve long term survival of 90% across Western co-operative group trials, published data from Asian studies on long term outcomes are scarce. We retrospectively analyzed the data of pediatric B-cell LBL patients treated between January 2010 and December 2017 on a uniform protocol (modified BFM 90). Kaplan-Meier method was used to estimate the survival and Cox regression models to identify prognostic factors. Of 21 patients who received treatment on the modified BFM-90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality (TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months (range 6-114), 5-year event free survival (EFS) and overall survival (OS) were 80% (95% CI:71-89%) and 91% (95% CI:85-97%), respectively. While delayed presentation from symptom onset (p=0.030), and partial response at early (D35) interim assessment (p=0.025) had inferior EFS, patients with elevated baseline LDH had a worse OS (p=0.037). Outcomes of pediatric B-cell LBL patients treated on a modified BFM-90 protocol at a single center in India were excellent. In our study, higher disease burden manifested by elevated baseline LDH and delayed presentation (≥3months) and partial interim response portend poorer survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2005725.

Atypical imaging presentation of herpes simplex virus encephalitis in paediatric immunocompromised oncology patients.

INTRODUCTION: We aim to assess the imaging manifestations of brain involvement in paediatric immunocompromised patients with haematological malignancies on chemotherapy presenting with encephalitis and positive HSV CSF PCR. We also aim to determine whether our findings are similar or different to those described in literature for paediatric patients in general. METHODS: A retrospective study was performed in paediatric ALL/lymphoma patients on chemotherapy, and cases with positive CSF HSV-PCR with at least one head MRI scan were included. On imaging, location(typical/atypical), post-contrast enhancement and haemorrhage/diffusivity/gliosis were evaluated. RESULT: A total of 28 scans were included in study from 16 patients fulfilling inclusion criteria, 12 (75%) HSV-1 and 4 (25%) HSV-2. Of the 16 initial scans (CT n = 10, MRI n = 6), 11 were normal (CT = 7, MRI = 4). Fourteen patients had follow-up MRI, of which two had normal scans. On the abnormal initial scan (5/16), only 20% had typical medial temporal/inferomedial frontal/cingulate involvement. Most had frontal (80%), parietal (60%) and non-medial temporal (40%) lesions. Abnormal diffusivity/haemorrhage was absent in all, and postcontrast enhancement was seen in 20%. On follow-up, more patients (33%) had typical medial temporal/inferomedial frontal/cingulate involvement. Widespread atypical site involvement of frontoparietal (75%), thalamus (58%), non-medial temporal (50%), occipital/basal ganglia (33%) and cerebellum (8%) was noted. Most lesions were cortical (91%)/subcortical (75%) with few periventricular lesions (58%). Few showed abnormal diffusivity (16%), post-contrast parenchymal enhancement/haemorrhage (8%), post-contrast meningeal enhancement (25%) and gliosis (16%). CONCLUSION: Immunocompromised paediatric patients with haematological malignancies have widespread atypical brain involvement in herpes simplex encephalitis with lack of diffusion restriction and post-contrast enhancement, likely due to haematogenous spread of HSV across the blood-brain barrier, lack of cellular immunity and limited inflammatory cytokine response.

Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer.

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

FDG PETCT for assessing marrow involvement at staging pediatric nonhematological round cell malignancies.

BACKGROUND AND HYPOTHESIS: Bone and lung are the common sites of metastasis in pediatric round cell tumors and its presence indicates poor outcomes. Staging workup for these malignancies thus includes bone marrow biopsy (BMB) along with evaluation of thorax, and tissue analysis for N MYCN status in neuroblastoma. BMB is an invasive procedure requiring general anesthesia with known disadvantages.With an aim of avoiding an invasive BMB a study was taken up to evaluate efficacy of FDG PET CT in detecting marrow involvement in neuroblastoma and rhabdomyosarcoma at staging. MATERIALS AND METHOD: Prospective observational study evaluated 83 newly diagnosed treatment naïve patients of neuroblastoma (n = 43) and rhabdomyosarcoma (n = 42) who underwent conventional imaging of PETCT with CECT of local region along with a CT thorax and BMB (both iliac crest) done within 1 week. Findings of FDG PETCT were compared with bone marrow histology and accuracy parameters were calculated. RESULT: The overall sensitivity, specificity, accuracy, positive-predictive value (PPV), negative-predictive value (NPV) of FDG PETCT for detection of marrow disease was 100%, 86.1%, 89.4%. 68.9% and 100%, respectively. Subset analysis showed sensitivity, specificity, PPV and NPV of 100%, 66%, 71.4% and 100%, respectively, for neuroblastoma, with rhabdomyosarcoma patients having few events NPV of 100% accuracy of 97.6%. CONCLUSION: FDG PETCT with sensitivity and NPV of 100% can be considered as a first stop imaging and biopsy can be avoided in patients with a negative scan.

Feasibility of Nonanatomical Liver Resection in Diligently Selected Patients with Hepatoblastoma and Comparison of Outcomes with Anatomic Resection.

INTRODUCTION: Treatment guidelines for hepatoblastoma discourage nonanatomic liver resections. However, the evidence for this is inadequate and comes from a study performed almost two decades ago which additionally contained inherent limitations. This study aimed to assess the feasibility and oncologic outcomes of nonanatomic resections (NAR) performed in diligently selected patients and compare the results with anatomic resections (AR). MATERIALS AND METHODS: A total of 120 patients who underwent liver resections for hepatoblastoma between January 2008 and July 2019 were reviewed. Feasibility of NAR was based on postchemotherapy relations to vessels, site of the lesion, and possibility of achieving negative resection margins. RESULTS: AR was performed in 95 patients and 25 had NAR. The NAR cohort had similar International Childhood Liver Tumors Strategy Group (SIOPEL) risk group distribution. Blood loss and operative times were lower in patients undergoing NAR. No differences were noted between the two groups concerning postoperative morbidity and hospitalization. There were no pathologic positive margins or local recurrences in the NAR patients. Relapse free (RFS) and overall survival (OS) was similar in the two groups (p = 0.54 and 0.96, respectively). Subgroup analysis of only posttreatment extent of tumor (POSTTEXT) I and II patients also showed no difference in RFS or OS for the two groups with a persistent significant difference in operative times and blood loss. CONCLUSION: NAR is feasible with clear margins in carefully selected patients. It is not associated with more complications and outcomes are not inferior to AR. NAR is associated with lesser blood loss and operative time.

Intravascular extension of Wilms tumor: Characteristics of tumor thrombus and their impact on outcomes.

BACKGROUND: Studies describing intravascular involvement in Wilms tumor have focused on illustrating individual institutional experience and the elements of surgical management. Thrombus characteristics like extent, patterns of regression, and correlation with the surgical findings, intraluminal adhesion, and viable tumor in the thrombus, and patency of the inferior vena cava (IVC) have not been systematically described. OBJECTIVES: The aim of this study is to evaluate these thrombus characteristics and explore their impact on the overall outcomes. METHODS: All patients with histologically confirmed Wilms tumors with intravascular thrombus diagnosed in the pediatric oncology unit of Tata Memorial Hospital registered from 2006 to 2019 were included. Data regarding clinical, radiological, and surgical particulars were retrieved from the prospectively maintained institutional database. Specific data for the thrombus included: distal extent before and after neoadjuvant chemotherapy, correlation of extent with the surgical findings, completeness of thrombectomy, the presence of a viable tumor in the thrombus, and the patency of the IVC. Survival analysis was performed utilizing the Kaplan-Meier method on SPSS software version 25. RESULTS: The study included 43 (9.9%) of the 432 patients with Wilms tumor having intravascular extension. Retrohepatic IVC (33.3%) followed by atrioventricular (26%) formed the frequent levels of thrombus with maximum regression occurring after chemotherapy in the latter (Summary figure). The overall concordance rate between computed tomography (CT) scan and surgical findings for the presence of thrombus was 86% and 4 patients had the thrombus limited to a lower level than the preoperative scan. At a median follow-up of 5-years, the 5-year event-free and overall survival was 81% and 82.2% respectively. Atrioventricular thrombus (p = 0.003) and postoperative patency of IVC (p = 0.02) were significantly associated with inferior survival, while the extent of regression, thrombus fracture, and viability was not significant. DISCUSSION: The findings of this study bring forth the characteristics of intravascular tumor thrombus affecting the outcomes which can be validated in future prospective studies. Although the ideal method for radiological assessment of the intravascular thrombus is elusive, CT scan provided adequate information for the presence and level of the intravascular thrombus with reasonable accuracy in this study. Study limitations include small sample size, the limited number of events, and lack of multivariate analysis to rule out confounding factors that could influence the observed findings. CONCLUSION: Atrioventricular thrombus and occlusion of IVC represent adverse prognostic factors. The extent of regression, fracture, and viability of thrombus did not affect survival in this study.

Standardizing lymph nodal sampling for Wilms tumor: A feasibility study with outcomes.

BACKGROUND: Despite being mandated by cooperative groups, omission of nodal sampling is the most frequent protocol deviation in surgery for Wilms tumor. The stations as well as the number of nodes that should be sampled are not clearly defined resulting in a marked variation in practices among surgeons. We propose a systematic method for nodal sampling intending to reduce interoperator variation. In this study, we have assessed the feasibility and yield of systematic lymph node sampling and also evaluated the factors influencing nodal metastasis. METHODS: Prospective evaluation of 113 Wilms tumor patients operated at a single tertiary cancer center between 2015 and 2019. All these patients underwent a systematic 5-station nodal sampling. RESULTS: Median lymph node yield was 8 and 13.2% (15/113) patients harbored a histologically positive nodal disease. Of the patients with positive nodal disease, interaortocaval nodes had metastasis in 46.7% (n = 7). They represented isolated sites of nodal disease (skip metastases) in 28.6% (n = 4) of patients. Right-sided tumors had more frequent involvement of interaortocaval nodes and skip disease. Tumors with high-risk histology had 12.5 times more odds of harboring nodal disease as compared to low and intermediate-risk histology Wilms tumor. CONCLUSIONS: The proposed method of systematic station wise sampling provides a template to guide surgeons in performing lymph node harvesting. Interaortocaval nodes sampling should be performed routinely as the incidence of disease at this station is sufficiently high and metastasis may skip hilar nodes. STUDY OF DIAGNOSTIC TEST: Level III evidence.

Outcomes with nondose-dense chemotherapy for Ewing sarcoma: A practical approach for the developing world.

BACKGROUND: The current multidisciplinary approach in the treatment of Ewing sarcoma has improved cure rates, with contemporary dose-dense chemotherapy attaining 5-year event-free survival (EFS) of 73% in localized cases. Dose-intense and dose-dense chemotherapy is difficult in the majority of resource-limited settings with limited access to optimal supportive care. We report on patients with Ewing sarcoma treated on EFT-2001, a nondose-dense chemotherapy protocol. PROCEDURE: A retrospective analysis was conducted of patients (<15 years) with Ewing sarcoma treated with curative intent during January 2013-June 2017 with an institutional ethics committee-approved nondose-dense protocol (EFT-2001). Local therapy was planned after 9-12 weeks of chemotherapy with metastatic sites addressed with radiotherapy. The study assessed outcomes and prognostic factors. RESULTS: We analysed 200 patients with M:F ratio of 1.27:1 and metastases in 41 patients (20.5%). At a median follow up of 41.5 months (range 4.5-81.8 months), respective 3-year EFS and overall survival (OS) of the whole cohort is 65.3% (95% confidence interval [CI]: 58.1-71.7%) and 79.3% (95% CI: 72.8-84.5%); for localized and metastatic cohort, 70.9% (95% CI: 62.9-77.5%) and 82.8% (95% CI: 75.7-89.0%); and for metastatic cohort, 42.8% (95% CI: 28.0-58.6%) and 65.3% (95% CI: 47.7-78.3%). Presence of residual disease (morphologic/metabolic) on positron emission tomography-computed tomography scan done 3 months post definitive radiotherapy (hazard ratio [HR] 7.92 [95% CI: 3.46-18.14]) and delay in any form of local control >4 months (HR 3.42 [95% CI: 1.32-8.89]) affected outcomes. Nonrelapse mortality during treatment was 6.5%, mainly due to cardiomyopathy (3.0%) and bacterial sepsis (1.5%). Cardiotoxicity was seen in 11.5% of patients. CONCLUSIONS: Nondose-dense chemotherapy provides good outcomes with manageable toxicities in a multidisciplinary treatment approach, while reducing cumulative drug exposures in the developing world where dose-intense or dose-dense chemotherapy could potentially increase toxicity, and hence seems a feasible approach in resource-limited settings. Presence of any residual disease post definitive radiotherapy or delay in local control portends poor outcome.

A Retrospective Analysis of Invasive Fungal Diseases (IFD) of the Central Nervous System in Children With Lymphoid Malignancies.

BACKGROUND: Outcomes of childhood hematolymphoid malignancies have improved several fold because of immunosuppressive chemotherapy and broad-spectrum antibiotics for managing febrile neutropenia. An apparent trade-off has been an increase in invasive fungal disease (IFD), affecting multiple organs. We report the diagnostic and therapeutic challenges in 8 children with lymphoid cancers who developed intracranial (IC) fungal abscesses between 2010 and 2017. METHODS: Children below 15 years of age undergoing treatment for leukemia/lymphoma with clinicoradiologic and microbiologic evidence of IC fungal abscess were included. Demographic details, clinical profile, and management were retrospectively audited. Treatment was guided by European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions for IFD with therapeutic drug monitoring (TDM)-directed azole dosing, and surgical intervention. RESULTS: Eight patients (4 B-cell acute lymphoblastic leukemia, 2 relapsed B-cell acute lymphoblastic leukemia, and 2 non-Hodgkin lymphoma) were eligible for analysis. Proven, probable, and possible IFDs were seen in 2 (25%), 4 (50%), and 2 (25%) patients, respectively. Proven IFDs were invasive mucormycosis with remaining having mold infections. Cerebrospinal fluid galactomannan was positive in all 4 patients in whom it was tested. TDM was possible in 5/8 (63%) patients. Antifungal therapy was given for a median period of 4.2 months with 5 (63%) patients having complete resolution. Three (37%) patients expired, of which 2 were attributable to IFDs. CONCLUSIONS: IC fungal abscesses in children can cause significant morbidity and mortality in children with hematolymphoid cancers. Evaluation of cerebrospinal fluid galactomannan may help in early diagnosis and therapy. Prolonged antifungal therapy steered by TDM can help achieve resolution in some cases.

Favorable outcomes and reduced toxicity with a novel vinblastine-based non-high dose methotrexate (HDMTX) regimen (modified MCP-842) in pediatric anaplastic large cell lymphoma (ALCL): experience from India.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma (NHL) in children. Most treatment regimens include high-dose methotrexate (HDMTX), which is logistically difficult to administer in resource-limited settings. We evaluated the outcomes of pediatric ALCL patients treated on a uniform protocol (Modified Multicentric Protocol, MCP-842 regimen) at our hospital between January 2005 and December 2016. Of the 68 patients who received treatment on the Modified MCP842 protocol, 46 patients are alive in remission, 11(16%) had disease progression, 9(13%) relapsed after achieving remission, and 5(7%) had treatment-related mortality (TRM). Seventeen of 20 relapsed/progressed patients subsequently expired. With a median follow-up of 55 months (range 2-165 months), the 4-year event-free survival (EFS) and overall survival (OS) are 63% (95% CI of 50-73%) and 70%(95% CI of 57-79%), respectively. An indigenous protocol using vinblastine (without HDMTX and steroids) is feasible in a resource-limited setting and achieves outcomes comparable to regimens incorporating HDMTX, with lower toxicity.

Customized approach for upfront or delayed resection using radiological criteria in unilateral, nonmetastatic pediatric renal tumors: A prospective study.

BACKGROUND: The availability of robust, equivalent data regarding outcomes for upfront or delayed surgery for renal tumors in children leads to a dilemma in selecting the initial treatment. Imaging criteria associated with the probability of rupture or incomplete resection may provide a more objective assessment for customization for the timing of surgery. PROCEDURE: Eighty-three children with unilateral, nonmetastatic renal tumors were enrolled between January 2012 and April 2018. Upfront nephrectomy was performed in the absence or delayed surgery (after a biopsy and chemotherapy) in the presence of one or more imaging-based high-risk features, including perinephric spread or adjacent organ infiltration, tumors crossing the midline, intravascular thrombus, and extensive adenopathy. Post hoc analysis for interobserver concordance for high-risk imaging features was also performed. RESULTS: The upfront surgery group (19) had predominantly stage I or II diseases (89%) and the histological types were Wilms (13), non-Wilms (5) renal tumor, and an inflammatory lesion. The delayed surgery group had 60% with stage I or II diseases and the histological types were Wilms (60) and non-Wilms (4) tumor. In addition, high-risk pathology was identified in nine patients. Overall, 27 patients with Wilms tumors required radiotherapy and anthracycline because of stage III disease, including one in the immediate surgery group. The event-free and overall survival (OS) at a median follow-up of 39 months for Wilms tumor are 88% (95% confidence interval [CI]: 78.5-94.9%) and 89% (95% CI: 81.4-96.6%), 85.1% (95% CI: 73.8-93.4%) and 86.5% (95% CI: 77.4-95.8%) for the delayed, and 100% event-free survival as well as OS (P = .1) in the upfront surgery group. CONCLUSION: A customized approach pivoted on image-based high-risk features facilitates identification of patients with early-stage renal tumor when the timing of surgery is tailored. Moreover, non-Wilms tumor and high-risk pathology are also identified.

Breast cancer in a tertiary cancer center in India - An audit, with outcome analysis.

BACKGROUND: Survival studies may serve as benchmarks to develop cancer-related policies and estimate baseline survival rates in a given patient population. MATERIALS AND METHODS: We carried out a retrospective audit of cases managed in 2009 and now report the disease-free survival (DFS) in early breast cancer (EBC) and locally advanced breast cancer (LABC) in patients registered at a tertiary cancer center in India. RESULTS: The study included 2192 patients with breast cancer with ages ranging from 18 years to 94 years with a median of 50 years. Of these, 888 (40.5%) were EBCs Stage I and II, 833 (38%) were LABCs (Stage III), and 471 (21.5%) were de novo metastatic or relapsed cancers at presentation. The 5-year DFS in the women with EBC was 85.5% and in LABC, it was 67.7%, P < 0.001. The factors adversely affecting DFS in EBC were node metastasis (P < 0.001), higher metastatic nodes (P < 0.001), hormone receptor negativity (P = 0.001), and human epidermal growth factor receptor 2 (Her2neu) positivity (P = 0.033). In the multivariate Cox regression analysis in EBC, node-positive status (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.51-3.45, P < 0.001) and hormone receptor negative tumors (HR 1.96, 95% CI 1.30-2.94, P = 0.001) significantly affected DFS in EBC. The factors adversely affecting DFS in LABC in the univariate analysis were node metastasis (P < 0.001), increasing numbers of nodes (P < 0.001), presence of lymphovascular emboli (LVE) (P < 0.01), mastectomy (P < 0.001), and Her2neu positivity (P = 0.03). In the multivariate Cox regression analysis, node positivity (HR 2.96, 95% CI 2.04-4.29, P < 0.0001), presence of LVE (HR 1.47, 95% CI 1.06-2.04, P = 0.023), and mastectomy (HR 1.49, 95% CI 1.06-2.10, P = 0.023) adversely impacted DFS in LABC. CONCLUSIONS: The survival rates in this study are equal to the documented global rates; nodal disease burden emerged as the most important prognostic factor. In addition, in EBCs, a lack of hormone receptor expression and in LABC, Her2neu overexpression appear to worsen the outcome.

A cross-sectional study of the distribution of pediatric solid tumors at an Indian tertiary cancer center.

CONTEXT: Pediatric solid tumors include a heterogeneous group of tumors, and the burden of these tumors, especially from resource-challenged countries, is not well described. AIMS: The aim of this study was to describe the distribution of solid tumors in children and the treatment outcome of Wilms tumor and hepatoblastoma. PATIENTS AND METHODS: All patients under 15 years of age with histologically confirmed tumors presenting at a tertiary cancer center from January 2012 to December 2016 were identified from the hospital database. Patients with lymphomas, bone, and central nervous tumors were excluded. The demographic profile including age, sex distribution, and the treatment received were recorded for all patients. RESULTS: The mean age of the eligible 1944 patients was 5.7 years with majority (57.3%) in the 0-4 years age group. The male-to-female ratio was 1.4:1 with a male predominance in all tumors except germ cell tumors. Soft tissue tumors were the most common tumors followed by neuroblastoma and renal tumors, whereas liver tumors formed only 6.7% of all tumors. Seventy percent of the patients received treatment completely or partially at our institute, whereas 18.3% had no cancer-directed treatment. The 3-year overall survival of patients with Wilms tumor and hepatoblastoma was 85.4 and 78.5%, respectively. CONCLUSIONS: Extracranial and extraosseous pediatric solid tumors include a wide range of tumors with a predilection for male sex and children below 4 years of age. Soft tissue tumors, neuroblastoma, and renal tumors are the most common; the outcomes of Wilms tumor and hepatoblastoma are favorable.

Outcomes and complications of surgery in patients with intermediate-risk neuroblastoma: experience from an Indian tertiary Cancer Centre.

PURPOSE: The treatment of intermediate risk (IR) neuroblastoma has evolved with the focus now on reducing the drugs, dosage, and duration of chemotherapy. The aim of this study is to present the outcomes of treatment and the complications of surgery in patients with IR neuroblastoma treated at a tertiary cancer center in India. METHODS: All eligible patients with IR neuroblastoma treated between April 2005 and August 2016 were identified. The presence and number of image-defined risk factors (IDRF) before and after neoadjuvant chemotherapy were retrospectively analyzed as were the extent of surgery, complications, and outcomes. RESULTS: Of 282 neuroblastoma patients treated during the study period, 54 had IR neuroblastoma. Complete excision was achieved in 25 patients. There were 26 surgical complications in 22 patients with a similar incidence in patients with complete (n = 13) or incomplete (n = 13) resection (p = 0.78). After a median follow-up of 47 months, the 4-year overall and event-free survival was 91.5% and 75%, respectively. There was no difference in survival between patients who underwent complete resection versus those with incomplete resection (p = 0.9). CONCLUSION: Outcomes of IR neuroblastoma are favorable. The extent of resection does not affect the survival and complications can occur even when the resection is incomplete.