Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

BACKGROUND OBJECTIVES: The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. METHODS: A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. RESULTS: Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. INTERPRETATION CONCLUSIONS: Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

Cardiac function in pediatric Ewing sarcoma during and after treatment: A longitudinal study.

BACKGROUND: While anthracycline therapy has been shown to improve outcomes in Ewing sarcoma, it may be associated with severe and even fatal cardiac dysfunction. We evaluated the burden and determinants of cardiac dysfunction in pediatric Ewing sarcoma (pES). METHODS: This retrospective study included children aged 0-18 years with pES treated at our center with the EFT 2001 protocol (anthracycline and cyclophosphamide containing regimen), with/without radiation therapy from January 2001 to December 2018. Cardiac dysfunction was defined as left ventricular (LV) ejection fraction with an absolute value <50%. RESULTS: Amongst 650 eligible patients (median age at diagnosis 12 years and median follow-up duration 69 months), 85 (13%) developed cardiac dysfunction, at a median 13 months (range: 1-168 months). The cumulative incidence of cardiac dysfunction was 5.7% at 12 months, 12% at 2 years, 13% at 3 years, 14% at 5 years, and 15 % at 10 years. At a median follow-up duration of 25 (range: 3-212) months, 21 (24.7%) patients had normalization of LV function, whereas nine (10.6%) patients died of cardiac causes. Older age at diagnosis (7-12 years OR 5.1, p = .01, 13-18 years, OR 3.9, p = .03), female sex (OR 2.3, p = .004), undernutrition (OR 2.9, p = .001), and chest wall location (OR 8.7, p = .08) were risk factors for cardiac dysfunction. CONCLUSIONS: Children with Ewing sarcoma have a high incidence of cardiac dysfunction, which continues to develop even years after therapy, underlining the need for life-long surveillance. Undernourished children are at a higher risk for cardiac dysfunction and need stringent monitoring.

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).

Treatment outcomes and prognostic factors in children with hepatoblastoma using a risk-stratified approach.

BACKGROUND: Not all the significant progress made in the management of children with hepatoblastoma (HB) has translated into improved outcomes in limited-resource settings. There are limited data on outcomes in children with HB from India. METHODS: All patients diagnosed with HB between July 2013 and December 2020 were risk-stratified and treated as per International Liver Tumor Strategy Group (SIOPEL). Patients with standard-risk HB received cisplatin monotherapy and those with high-risk HB received alternating cycles of cisplatin and the combination of carboplatin plus doxorubicin. Data regarding demographic details, chemotherapy, surgery, liver transplantation, outcomes, prognostic factors, and toxicity were collected. RESULTS: Of 157 patients with HB, 117 (74%) were high risk, 31 (20%) were standard risk, and nine (6%) unknown. Patients with standard-risk disease had excellent outcomes, with 3-year event-free survival (EFS) and overall survival (OS) of 96% and 100%, respectively. Among high-risk HB, six underwent orthotopic liver transplantation of which four were alive at last follow-up. The 3-year EFS and OS of patients with high-risk disease was 56% and 66%, respectively. Outcomes of patients with PRETEXT IV (3-year EFS: 42%, 3-year OS: 50%) and metastatic disease (3-year EFS: 30%, 3-year OS: 50%) were dismal. Patients with serum alpha-fetoprotein (AFP) reduction greater than 90% following two courses of chemotherapy had favorable outcomes; 3-year EFS: 80% versus 58% (p = .013) and 3-year OS: 95% vs. 68% (p < .01). Only two (6%) of 31 patients with relapse/refractory HB were alive at a median follow-up of 36 months, and both had received salvage chemotherapy and surgery. CONCLUSIONS: While children with standard-risk HB had excellent outcomes, those with high-risk disease continue to do poorly. Serial monitoring of serum AFP values is a cost-effective and reliable predictor of outcomes. Orthotopic liver transplantation remains a viable option for inoperable disease in resource-limited settings as well.

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.

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.

Solitary Bone Plasmacytoma of Humerus Presenting as a Nonhealing Fracture in a Child: A Rare Entity.

Solitary bone plasmacytoma is an extremely rare entity and is characterized by localized proliferation of monoclonal plasma cells. Plasmacytomas are extremely rare in the pediatric population. The median age at diagnosis is usually the fifth or sixth decade, with axial skeleton being more commonly involved than appendicular. We hereby, report the case of a 13-year-old boy with solitary bone plasmacytoma of the right humerus. Though extremely rare in the pediatric age group, plasmacytomas may be considered as one of the remote differentials in children presenting with solitary bone tumors.

Adolescent-adult nonmetastatic Ewing sarcoma-Experience from a large developing country.

BACKGROUND: Outcome and toxicity data in adolescent-adult Ewing sarcoma (AA-ES) patients are sparse and merits exploration. METHODS: Histopathologically confirmed, nonmetastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (Ewing's family of tumors-2001 [EFT-2001]) comprising of ifosfamide plus etoposide and vincristine, doxorubicin plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS), and overall survival (OS). RESULTS: There were 235 patients (primary safety cohort [PSC]) with median age of 23 (15-61) years; 159 (67.7%) were males, 155 (65.9%) had skeletal primary and 114 (48.5%) had extremity tumors. One hundred ninety-six (83.4%) were treatment naïve (primary efficacy cohort [PEC]) and of these 119 (60.7%) had surgery. In PEC, at a median follow-up of 36.4 (interquartile range [IQR] 20-55) months, estimated 3-year EFS and OS were 67.3% (95% CI 60.3-75.1%) and 91.1% (95% CI 86.7-95.7%), respectively. Of these, 158 (80.6%) complying with intended treatment, at a median follow-up of 39 (IQR 26-57) months had an estimated 3-year EFS of 68.2% (95% CI 60.3-76.1%). In multivariable analysis, good prognostic factors included longer symptom(s) duration (HR 0.93, 95% CI 0.86-0.994), ≥99% necrosis (HR 0.30, 95% CI 0.11-0.77), and treatment completion (HR 0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile neutropenia (119, 50.6%), anemia (130, 55.3%), peripheral neuropathy (37, 15.7%), with three (1.3%) chemo-toxic deaths. CONCLUSIONS: The outcomes of AA nonmetastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen can be considered a standard of care in AA-ES.

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.

Clinical profile and outcome of classical Hodgkin lymphoma treated with a risk-adapted approach in a tertiary cancer center in India.

BACKGROUND: Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center. PROCEDURE: Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18 FDG-PET-CT-based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late-response assessment [LRA]) if not in complete response (CR; Deauville < 4) at ERA. Stages IA/IB/IIA were low risk (LR) and received two cycles of ABVD (adriamycin/bleomycin/vinblastine/dacarbazine). Stages IAX/IBX/IIAX/IIB/IIIA were intermediate risk (IR), and stages IIBE/IIBX/IIIAE/IIIAX/IIIB/IVA/IVB were high risk (HR). Both received two cycles of OEPA (oncocristine/etoposide/prednisolone/adriamycin). Those in ERA-CR received two cycles of ABVD if LR, and two and four cycles of COPDac (cyclophosphamide/oncocristine/prednisolone/dacarbazine), respectively, for IR and HR. Involved-field radiotherapy (IFRT) was given to bulky sites and ERA < CR. Those at LRA < CR (Deauville < 3) or progression at any stage received salvage regimens. RESULTS: In the study period, 126 patients were identified who received the above protocol. There were 12 LR, and 114 advanced staged Hodgkin lymphoma (AHL) (18, IR; 96, HR) of which 91 (79.8%) had bulky sites. Eight (66.6%) LR and 93 (83%) AHL patients achieved ERA-CRs. IFRT was given to 4 (33.3%) LR patients with ERA < CR, and 92 (80.7%) of AHL (91 bulky sites; 1 ERA < CR). At a median follow-up of 31 months (range, 17-62), three-year event-free survival (EFS) and overall survival (OS) were both 100% for LR, and 94.4% (95% CI, 66.0%-99.2%) for IR, whereas for HR it was 90.3% (95% CI, 82.2%-94.8%) and 92.6% (95% CI, 85.2%-96.4%), respectively. CONCLUSIONS: Children with HL have favorable outcomes with manageable toxicities when treated on a risk-stratified and adapted approach. A high proportion of AHL have bulky disease necessitating IFRT, a concern that will have to be factored in future strategies.

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.

Unfavorable presentation but comparable outcome: Presentation and outcome of children with nodular lymphocyte predominant Hodgkin lymphoma from India.

BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL) with few published studies in children, entirely from North America and Europe. We analyzed clinical features and treatment outcome of pediatric NLPHL. PROCEDURE: Children less than 18 years of age diagnosed after histopathology review to have NLPHL between June 1998 and August 2016 were retrospectively analyzed. Descriptive details of clinical presentation and treatment were collected, and outcomes analyzed using Kaplan-Meier survival analysis. RESULTS: Of the 42 patients with a confirmed diagnosis of NLPHL during this period, there was complete information on 35. Median age was 11 years (range 6-16 years), male:female ratio was 4.8:1, there were 15, 11, 6, and 3 patients with Stage I, Stage II, Stage III, and Stage IV disease, respectively. Six patients had B symptoms, 10 had bulky disease, and 3 had bone marrow as well as extranodal involvement. Histology was typical NLPHL in 23 and variant in 12. Twenty-nine received chemotherapy, 10 with additional radiation, 3 patients with early stage disease received only radiotherapy and three others underwent complete node resection alone. Median follow-up was 55 months (range 7-165 months), 5 year event-free survival (EFS) was 83.3%, and overall survival 97.1%. Variant NLPHL histology was associated with higher incidence of unfavorable presentation and lower EFS. CONCLUSIONS: NLPHL in India has an excellent outcome, despite a higher incidence of unfavorable presentations such as advanced stage disease, B symptoms, and bulky disease. Variant histology is an adverse prognostic factor.

Interstitial brachytherapy for pediatric soft tissue sarcoma: Evolving practice over three decades and long-term outcomes.

PURPOSE: Evaluate long-term clinical outcomes, adverse effects, and evolving practice of interstitial brachytherapy (BT) for pediatric soft tissue sarcomas (STS). METHODS: From September 1984 to December 2014, 105 children (median age 10 years) were included. There were 60 males and 45 females. The majority (74%) had primary lesions. Synovial sarcoma (22%) was the most frequent histology. Treatment included wide local excision and BT with or without external beam radiotherapy (EBRT). Eighty-five (81%) received BT alone. RESULTS: After a median follow-up of 65 months, local control (LC), disease-free survival (DFS), and overall survival (OS) at 10 years were 83, 66, and 73%, respectively. On univariate analysis, LC was superior with tumors <5 cm versus >5 cm (93% vs. 75%, P = 0.10), Grade I/II versus Grade III tumors (97% vs. 73%, P = 0.01), nonround cell versus round cell histology (89% vs. 72%, P = 0.03), and trunk/extremity versus head and neck/genitourinary sites (87% vs. 57%, P = 0.0001). On multivariate analysis tumor size (P = 0.03) and location (P = 0.002) retained significance. Children receiving BT alone had comparable LC to those receiving BT and EBRT (84% vs. 80%, P = 0.43). There was no difference in LC between LDR versus HDR BT (86% vs. 83%, P = 0.30). Wound complications were seen in 6%. Subcutaneous fibrosis (25%), limb edema (6%), skeletal abnormalities (3%), and neuropathy (1%) were the late complications. One child (0.9%) developed a second malignancy after 7 years. CONCLUSION: Interstitial BT with or without EBRT results in excellent outcomes. Radical BT alone, when used judiciously, results in excellent local control and function with minimal treatment-related morbidity.

Clinicopathologic features of 300 rhabdomyosarcomas with emphasis upon differential expression of skeletal muscle specific markers in the various subtypes: A single institutional experience.

The present study was aimed at evaluating clinicopathologic and immunohistochemical (IHC) features of 300 rhabdomyosarcomas (RMSs), including differential IHC expression and prognostic value of myogenin and MyoD1 across various subtypes of RMSs. IHC expression of myogenin and MyoD1 was graded on the basis of percentage of tumor cells displaying positive intranuclear immunostaining i.e. grade 1 (1-25%); grade 2 (26-50%); grade 3 (51-76%) and grade 4 (76-100%).Clinical follow-up was available in 238 (79.3%) patients. Various clinicopathologic parameters were correlated with 3-year disease free survival (DFS) and overall survival (OS). There were 140 cases (46.7%) of alveolar RMS (ARMS), 90 of embryonal RMS (ERMS) (30%), 61 (20.3%) of spindle cell/sclerosing RMS and 9 cases (3%) of pleomorphic RMS. Most cases, barring pleomorphic RMSs, occurred in the first two decades (228 cases) (76%), frequently in males, in the head and neck region (126) (42%). By immunohistochemistry, desmin was positive in 292/299 (97.6%) tumors; myogenin in 238/267 (89.1%) and MyoD1 in 192/266 (72.2%) tumors. High myogenin expression (in ≥51% positive tumor cells) was significantly associated with ARMSs (95/121, 78.5%), as compared to other subtypes (48/117, 41%) (p value < 0.001). High MyoD1 expression (≥51% tumor cells) was seen in more cases of pure sclerosing, combined with spindle cell/sclerosing RMSs (10/10, 100%), as compared to the other subtypes (91/141, 67.4%) (p = 0.032). There was no significant difference between high myogenin expression and clinical outcomes. Patients without metastasis and harbouring tumors, measuring ≤5 cm showed a significant increase in OS, with p values = 0.01 and <0.001, respectively. ARMS was the most frequent subtype. There was a significant association between high myogenin expression and ARMSs and high MyoD1 expression and spindle cell/sclerosing RMSs. High myogenin expression did not correlate with clinical outcomes. Patients with smaller sized tumors and without metastasis had significantly better clinical outcomes.

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.

Benign liver tumors in children: outcomes after resection.

PURPOSE: Benign liver tumors in children are rare and data regarding the surgical outcomes are deficient. We reviewed our experience in the management of these tumors particularly the extent, safety, and effectiveness of surgical resection. METHODS: Between March 2005 and March 2014, 10/90 liver resections were performed for benign liver tumors. Three other patients received conservative treatment. Demographic characteristics, operative management, morbidity, and mortality were analyzed. RESULTS: The median age of the patients was 12 months. The distribution of pathology was infantile hepatic hemangioendothelioma/hemangioma (n = 7), mesenchymal hamartoma (n = 4), adenoma (n = 1) and focal nodular hyperplasia (n = 1). Median tumor size was 12.25 cm (range 3.5-21 cm) with a median tumor volume of 576.64 cm(3) (range 13.9-1822.64 cm(3)). Non-anatomic resection was performed in 6/10 patients and the median blood loss was 100 ml (range 10-850 ml). Median length of hospital stay was 7 days (range 5-9 days). There were no mortality, none of the patients had a local recurrence, and all are alive at a median follow-up of 33 months. CONCLUSIONS: Two-third patients with benign liver tumors were managed with surgical excision, which comprised 11% of our resectional practice. Non-anatomical resection whenever feasible can be performed safely and does not compromise the oncological outcomes.

Primary non-metastatic Ewing sarcoma of the jaw in children: results of surgical resection and primary reconstruction.

BACKGROUND AND OBJECTIVE: The rarity of Ewing sarcoma (ES) of the jaw coupled with the technical challenge of resection and associated functional and cosmetic impairment has resulted in deficient data on surgical management of these tumors. The purpose of this study is to describe the results of surgical excision and reconstruction of primary non-metastatic ES of the mandible and maxilla in children. METHODS: Consecutive patients (mandible = 6, maxilla = 5) treated with surgery from August 2005 to January 2013 were selected. All patients received induction chemotherapy and were selected for surgical resection based on the presence of specific criteria for operability. RESULTS: The median age was 11.5 years (range 5-16 years). Free fibular osteocutaneous flap was commonly used for reconstruction. There were no complications related to microvascular anastomosis or flap loss. Five patients had 100% tumor necrosis and did not receive radiotherapy. Teeth alignment, chewing, swallowing, and speech were normal in all and donor site morbidity occurred in one. The 5-year overall, event-free survival, and local control are 87.5%, 72.9%, and 90%, respectively. CONCLUSION: In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcome. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Outcome and morbidity of surgical resection of primary cervical and cervicothoracic neuroblastoma in children: a comparative analysis.

INTRODUCTION: Primary cervical (CN) and cervicothoracic neuroblastoma (CTN) is generally associated with good outcome; however, surgical resection can be challenging and not without morbidity. The aim of this study is to assess the overall outcome and compare the clinico-radiological features, treatment, and complications of CN and CTN. MATERIALS AND METHODS: Sixteen consecutive patients, (CN = 9, CTN = 7) treated between November 2006 and December 2012 were selected from the prospective database for this analysis. RESULTS: The 2-year overall and event-free survival of entire cohort is 100 and 72 %, respectively. Respiratory symptoms due to compression of airway and intraspinal extension were common in CTN. Gross total resection was feasible in all patients with CN; in contrast, incomplete excision along with significantly longer duration of surgery and more blood loss occurred in CTN. Postoperative morbidity was seen in three patients with CN and only one patient with CTN. The extent of surgery did not affect the overall and event-free survival of CTN (p = NS). CONCLUSION: CN and CTN have characteristic clinico-radiological presentation and surgical specification. However, both have a favorable outcome, even though with a distinct but acceptable morbidity. The favorable outcome in CTN is unrelated to the extent of surgical excision.

A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted EPOCH (+/-R) Regimen.

High-grade B-cell NHL's are more common in seropositive patients. They are biologically different from their seronegative counterparts. We report our analysis on our cohort of patients who were treated with DA-EPOCH(+/-R). We retrospectively analyzed treatment-naïve HIV-associated High-grade B-cell NHL patients (aged ≥ 18) treated with DA-EPOCH(+/-R) regimen from 2011 to 2015. Descriptive statistics were summarized with median and range; survival outcomes were analyzed with Kaplan-Meier method. The cohort comprised of 40 patients [DLBCL(19), Burkitt's Lymphoma(16), High-grade B-Cell Lymphoma-Unclassifiable(09), and Plasmablastic Lymphoma(01)] and the median CD4 + T cell count was 202/mm3. CNS prophylaxis was administered with intrathecal methotrexate to 90% of patients. With a median follow-up of 72 months, an estimated 5-year OS was 82.5%, and 5-PFS was 77.5%. There were 9 deaths, and 9 patients had progression. At least 4 cycles of chemotherapy were administered to 35 (93%) patients, with 28 (70%) receiving 6 cycles. Grade 3-4 toxicities were seen in 33 (83%) patients- febrile neutropenia (65%) being the most common followed by mucositis (25%) and peripheral neuropathy (13%). There was no difference in survival based on IPI, CD 4 + T cell count, CDI, or duration of HIV. DA-EPOCH(+/-R) is a highly effective regimen in seropositive high-grade B-cell lymphoma, even in the presence of adverse features. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01652-3.