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Aim: The outcome of patients with advanced gastrointestinal stromal tumor (GIST) has improved with the use of imatinib. Despite high response rates with this drug resistance eventually develops in nearly all patients. We present an analysis of prospectively collected data on sunitinib efficacy and safety in patients with imatinib-resistant GIST.Subjects and Methods: Between November 2006 and October 2007, patients with GIST were accrued in an approved sunitinib patient access protocol. Key eligibility criteria included tumor resistance to imatinib and/or patient intolerance to this drug. Patients received sunitinib at a starting dose of 50 mg once daily for 4 weeks in a 6 week cycle, with standardized dose modification titrated to toxicity. Patients were continued on sunitinib until disease progression or unacceptable toxicity. The endpoints were safety, overall survival (OS) and objective response rate (ORR).Results: Fifteen patients, all of whom had imatinib resistance and none intolerance, with median age of 48 (26-69) years, were treated on the protocol. The most common sites of primary disease were small intestine (40%), stomach (26.7%) and retroperitoneal (26.7%). A median of 10 (1-47) cycles of sunitinib were delivered, 9 (60%) patients required dose reductions due to toxicity whereas dose delay of > 2 weeks was required in only one (6.7%) patient. There were no toxicity-related drug discontinuations. Hypothyroidism (n = 4; 26.7%) and hand-foot syndrome (n = 3; 20%) were the most common toxicities. There were no complete and 4 (26.7%) partial responses while prolonged disease stability was seen in 8 (53.3%) patients. At a median follow-up of 81 months in surviving patients, the median progression-free and overall survivals were 15.5 and 18.7 months, respectively.Conclusions: Sunitinib appears to be an effective and well-tolerated treatment for Indian patients with imatinib-resistant GIST with outcomes similar to that reported previously. Adverse effects can be reasonably well managed using a dose modification strategy. [ABSTRACT FROM AUTHOR]

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Pleuropulmonary blastoma (PPB) is a rare and aggressive type of intrathoracic malignancy arising from pleuropulmonary mesenchyme predominantly seen in childhood. We evaluated the clinico-patho-radiological profile, treatment response, and overall outcomes for patients with PPB treated with curative intent protocols at the Tata Memorial Hospital (TMH). All patients with histologically confirmed PPB were retrospectively analyzed. Between December 2004 to June 2023, 26 patients (15 males) with histologically proven PPB in the age group of 2 to 22 years (Median 4 years) were evaluated at TMH. Clinico-radiological and treatment details were available for 19 patients. The mean tumor size in this cohort was 11.45cm. The presence of pleural effusion and intrathoracic nodes was observed in 10 (53%) and 5 (26%) patients, respectively. All of them presented with locally extensive and type II/III disease. Curative intent treatment was offered to 17 patients and 14 of them received upfront intensive multi-agent chemotherapy. Three patients underwent upfront surgery. Four out of fourteen (29%) patients progressed on induction chemotherapy and hence, did not undergo local treatment. Post neoadjuvant chemotherapy, out of the 9 patients, local treatment in the form of surgery was offered to 7 (64%) patients followed by adjuvant radiotherapy to 6 patients (38%), whereas 2 patients received definitive radiotherapy. At the time of last follow up only 5 out of 17 (29%) patients were alive and disease free. All patients who had progressive disease on chemotherapy and did not receive local treatment died of the disease. Of the 12 patients receiving local treatment, 4 died of local relapse. The 2-year and 3-year overall survival of the entire cohort were 47% and 35% respectively. PPB is associated with dismal outcomes. Patients responding to induction chemotherapy and receiving local treatment have better survival. [ABSTRACT FROM AUTHOR]

To evaluate treatment outcome of children diagnosed with unilateral retinoblastoma. Retrospective study of children diagnosed with unilateral retinoblastoma registered at our institute from January 2013 to December 2018 and completed the curative treatment protocol. For the 98 cases analyzed the median age was 24 months. At the time of presentation, 72 had intraocular and 26 had orbital. On imaging extra-scleral spread was observed in 16 patients whereas 18 patients had optic nerve (ON) involvement, 11 patients had both extra-scleral invasion and ON involvement. Majority we ICRB group E (71), and group D=21, group C= 2, group B=4. Majority were IRSS Stage 1(stage0=14, stage1=52, stage2=10, stage3a=21 and stage3b=1). High-risk features on surgical specimen histopathology were ON margin positivity in 6, ON involvement in 21, extra-scleral spread in 3, choroidal invasion in 38 and iris involvement in 10 patients. Eneucleation was offered to 78 (Primary=52, secondary=26). Chemotherapy was offered to 68 (chemoreduction=17, adjuvant chemotherapy=51). Intra-arterial chemotherapy was offered to 27 patients as a primary treatment or in conjugation with focal therapy (n=11). Definitive radiotherapy was offered to only 2 patients and 22 patients received adjuvant radiotherapy. At a median follow-up of 62 months, 2 patients had local relapse, which was salvaged by focal therapy in one and enucleation in the other. Ten patients who had leptomeningeal relapse had died. The 5-year local control (LC) is 97.6%, event-free survival (EFS) is 88% and overall survival (OS) is 89.5%. Globe was salvaged in only 16 cases. On univariate analysis, orbital disease, extra-scleral spread, ON involvement (imaging), and ON margin positivity, higher ICRB Group and IRSS stage had poor impact on OS. Retinoblastoma is curable with optimal globe salvage rates if detected early. Orbital disease, high risk features on surgical specimen histopathology and leptomeningeal relapse are associated with inferior outcomes. [ABSTRACT FROM AUTHOR]

This retrospective study evaluates the disease profile, treatment response, long term outcomes, and prognostic factors for patients ES of the head and neck region treated with curative intent and a homogeneous treatment protocol at our institute. From January 2005 to December 2020, 101 patients in the age group of 2months – 42years (Median 14years) were analysed after institutional ethics committee approval. Out of 101 patients, 62 (61%) were males and the mean tumour size was 5cms. All patients received multi-modality treatment, EFT 2001 systemic chemotherapy (CTh) and local treatment comprising of either surgery (Sx, n = 10), radiation therapy (RT, n = 43) or both (n =47) followed by maintenance CTh. One patient died during Induction CTh due to toxicity. RT alone was offered in cases where Sx was either not feasible or was deemed to be associated with significant morbidity. After a median follow-up of 61 months, the 5-year local control (LC), event free survival (EFS) and overall survival (OS) were 84.4%, 74% and 88.2% respectively. At last follow up, 77 (76%) patients were alive and disease free. Ten patients had local relapse only, 8 had distant metastases and 5 had both local plus distant relapse. The choice of local treatment (5-year OS - RT (89.9%) vs Sx plus RT(86.1%), p = 0.51) did not affect outcomes. On univariate analysis, stage, raised platelet-to-lymphocyte ratio and partial response to RT were significant prognostic factors for OS. There were no ≥ Grade 4 acute or late toxicities owing to local treatment modality. Multi-modality treatment using a combination of CTh, Sx and RT results in optimal disease control with acceptable toxicities. Definitive RT should be considered when surgery is not feasible or associated with significant morbidity. [ABSTRACT FROM AUTHOR]

The pathogenesis of gallbladder cancer presenting synchronously with malignancy of the bile duct has not been clearly understood. The possible causes for the simultaneous presence of these tumors could be due to local spread, metastases, de novo multifocal origin, or as part of a field change in the extrahepatic biliary apparatus. In this article, we discuss the cases of four patients with simultaneous gallbladder and bile duct malignancies and analyze their individual pathologies to provide an explanation into the mechanisms that may play a role in such conditions. [ABSTRACT FROM AUTHOR]

Background: The care of adolescents and young adults (AYAs) with bone sarcomas involves unique challenges. The objectives of this study were to identify challenges and evaluate long-term outcomes of these patients from India who received treatment with novel protocols., Methods: This prospective cohort study included AYA patients (aged 15-39 years) with osteosarcoma and Ewing sarcoma (ES), who were treated uniformly at the authors' institute using unique protocols (OGS-12 and EFT-2001) from 2011 to 2021 and from 2013 to 2018, respectively., Results: The cohorts included 688 of 748 (91.9%) treatment-naive AYA patients with osteosarcoma and 126 of 142 (88.7%) treatment-naive AYA patients with ES. Among 481 of 561 patients (85.7%) who had nonmetastatic osteosarcoma treated according to protocol, at a median follow-up of 59.7 months, the 5-year event-free survival (5-EFS) rate was 58.6% (95% confidence interval, 54.1%-63.5%) and for 142 patients (20.6%) who had metastatic osteosarcoma, the 5-EFS rate was 18.7%. The 5-EFS rate was 66.4% and 21.9% for 104 patients (73%) with nonmetastatic ES and 38 patients (27%) with metastatic ES, respectively. Treatment-naive patients had better outcomes, similar to compliance in the form of protocol completion (hazard ratio, 1.93 [p = .0043] and 2.66 [p < .0001], respectively. Only 230 of 377 (61.0%) male patients and 10 of 134 (7.4%) female patients reached out to fertility specialists. In addition, 17 of 161 (10.6%) eligible male survivors and 14 of 61 (22.9%) eligible female survivors got married posttreatment. Furthermore, 14 of 17 (82.4%) males and 14 of 14 (100%) females conceived. Among 311 patients who were working or attending school during diagnosis, greater than 90% had interruptions., Conclusions: Homogenous treatment with the OGS-12 and EFT-2001 protocols resulted in internationally comparable long-term outcomes in the cohorts with nonmetastatic and metastatic AYA bone sarcomas. Treatment compliance, timely referral to sarcoma reference centers (avoiding prior inadvertent treatment), and streamlining fertility-preservation practices constitute unmet needs that demand prioritization., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Histopathological response to neoadjuvant chemotherapy (NACT) measured as tumor necrosis (TN) has been reported to be prognostic post-high-dose methotrexate (HDMTX)-based chemotherapy. We studied this on a non-HDMTX chemotherapy backbone., Materials and Methods: Children ≤15 years, with osteosarcoma treated on OGS-2012 protocol and surgery post NACT from January 2013 to December 2020 were retrospectively analyzed. TN was expressed as percentage. Outcomes based on different TN cutoffs (used in a dichotomized manner dividing the cohort into two groups of less than/greater than the particular cutoff) and clinical-laboratory parameters predictive of TN were studied., Results: Analysis was done in 258 patients. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38 months (range: 34-45 months), 3-year event free survival (EFS) and overall survival (OS) of the whole cohort were 56.1% (SE: 3.3%) and 87.8% (SE: 2.4%). For entire cohort, TN-70% (29.3% vs. 60.7%), 90% (38.7% vs. 69.0%), 100% (50.8% vs. 84.1%), were prognostic for EFS (p = 0.0001), while TN-90% (80.3% vs. 92.9%, p = 0.006) and 100% (85.5% vs. 97.7%, p = 0.023) were prognostic for OS. For localized disease, TN-70% (35.4% vs. 66.4%), 90% (41.6% vs. 77.0%), 100% (54.8% vs. 96.2%) were prognostic for EFS (p = 0.0001) and OS (p = 0.0001). For metastatic disease, TN-70% was prognostic for EFS (16.6% vs. 50.1%, p = 0.0047). Receiver-operator curve derived cutoff of 85.5% TN for EFS, 83.5% TN for OS prognosticated whole and localized cohorts the best. For metastatic cohort, 84.5% TN best prognosticated EFS. Among clinical-laboratory parameters, male gender (OR: 1.9, p = 0.01) and amputation (OR: 2.1, p = 0.014) had a higher risk of less than 90% TN., Conclusions: Tumor necrosis at 90% cutoff in localized disease is prognostic of survival even on a non-HDMTX-based backbone, but exploring other cutoffs for survival predictive and prognostic value could guide future treatment modification strategies and resource allocation in LMICs. Amputation, male gender predicts poor histological necrosis., (© 2024 Wiley Periodicals LLC.)