Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

PURPOSE: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non-high-income setting, with international input to evaluate the necessity of MTB in clinical practice. METHODS: We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented. RESULTS: Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases). CONCLUSION: The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.

Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial.

The benefit of three-drug induction chemotherapy over a two-drug induction has not been evaluated in pediatric acute myeloid leukemia (AML). We, therefore, conducted a randomized controlled trial to ascertain the benefit of a three-drug induction regimen. Patients aged 1-18 years with newly diagnosed AML were randomized to two cycles of induction chemotherapy with daunorubicin and ara-C (DA) or two cycles of ara-C, daunorubicin, and etoposide (ADE). After induction, patients in both arms received consolidation with two cycles of high-dose ara-C. The study's primary objective was to compare the event-free survival (EFS) between the two arms. The secondary objectives included comparing the composite complete remission (cCR) rates, overall survival (OS), and toxicities. The study randomized 149 patients, 77 in the DA and 72 in the ADE arm. The median age was 8.7 years, and 92 (62%) patients were males. The median follow-up was 50.9 months. The cCR rate in the DA and ADE arm were 82% and 79% (p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm (p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively (p = 0.66). The 5-year OS in the DA and ADE arms was 41.4% and 42.09%, respectively (p = 0.74). There were no significant differences in toxicities between the regimens. There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric AML. The trial was registered with the Clinical Trial Registry of India (Reference number: CTRI/2014/11/005202).

A red herring, a wild-goose chase, and an unexpected diagnosis of concomitant malignancy and sarcoidosis.

A 49-year-old male was evaluated in our hospital for chronic cough, cervical lymphadenopathy, and a testicular mass. As a part of the management, he underwent a cervical lymph node biopsy, which showed metastatic deposits from papillary carcinoma thyroid. Subsequently, he underwent orchidectomy for suspected testicular malignancy, but the biopsy showed discrete granulomatous inflammation consistent with sarcoidosis. This was followed by total thyroidectomy with neck node dissection. Nodal histopathological examination, this time, revealed a single node containing both malignancy and granulomas. Prior to the thyroid surgery, he underwent a mediastinoscopic sampling of the mediastinal nodes, which also showed granulomatous inflammation consistent with sarcoidosis. Sarcoidosis affecting the genitourinary system is a rare entity. The coexistence of sarcoidosis and thyroid malignancy poses a diagnostic challenge. A thorough review of the literature was done, and there are no reports from India on the above association. This is a unique case, which could possibly suggest an association between sarcoidosis and malignancy and highlights the importance of obtaining a tissue diagnosis in such cases.

Management of a case of Candida albicans endogenous endophthalmitis with intravitreal caspofungin.

We report a case of Candida albicans endogenous endophthalmitis treated with intravitreal caspofungin. The patient was a known case of acute lymphoblastic leukemia on chemotherapy and presented to us with features suggestive of endogenous endophthalmitis. He was treated initially with intravenous (IV) caspofungin and intravitreal amphotericin B. Patients condition worsened after IV caspofungin was replaced by amphotericin B necessitating a core vitrectomy. The patient was given the option of off-label caspofungin intravitreal injection for which the patient consented. There was a gradual improvement in the clinical picture. The situation worsened after the injections were stopped necessitating a revitrectomy. The study demonstrates the clinical efficacy of intravitreal caspofungin for the first time in human eyes.

Acute Myeloid Leukemia in Children: Experience from Tertiary Cancer Centre in India.

There is paucity of data in pediatric Acute Myeloid Leukemia (AML) from developing countries. We analyzed the outcomes of 65 consecutive patients with pediatric AML treated at our centre from January-2008 to May-2013. The median event free survival (EFS) and overall survival (OS) were 12.6 and 14.6 months respectively. Patients with good-risk cytogenetics had a better EFS (p = 0.004) and OS (p = 0.01). Overall, these results are not comparable to that observed in other centres globally and leaves scope for further improvement. This includes implementing allogeneic bone marrow transplantation as a treatment for all children with high-risk AML.