Tata Memorial Hospital

About: Tata Memorial Hospital is a healthcare organization based out in Mumbai, India. It is known for research contribution in the topics: Cancer & Breast cancer. The organization has 3187 authors who have published 4636 publications receiving 109143 citations.

ALK Positive Lung Cancer: Clinical Profile, Practice and Outcomes in a Developing Country

Abstract: Objectives To evaluate the performance and treatment profile of advanced EML4—ALK positive Non-small cell lung cancer (NSCLC) patients in a developing country with potentially restricted access to Crizotinib. Materials and Methods A retrospective analysis of advanced ALK positive NSCLC patients who were treated from June 2012 to September 2015 was conducted. The primary goal was to evaluate outcomes of advanced ALK positive NSCLC in our practice and examine the logistic constraints in procuring Crizotinib. Results 94 patients were available for analysis. 21 (22.3%) patients were started on Crizotinib upfront, 60 (63.8%) on chemotherapy, 10 (10.6%) on Tyrosine kinase inhibitors (in view of poor PS) and 3 (3.2%) patients were offered best supportive care. Reasons for not starting Crizotinib upfront included symptomatic patients needing early initiation of therapy (23.3%), ALK not tested upfront (23.3%) and financial constraints (21.9%). 69 patients (73.4%) received Crizotinib at some stage during treatment. Dose interruptions (> 1 week) with Crizotinib were seen in 20 patients (29%), with drug toxicity being the commonest reason (85%). Median Progression free survival (PFS) on first line therapy for the entire cohort was 10 months, with a significant difference between patients receiving Crizotinib and those who did not ever receive Crizotinib (10 months vs. 2 months, p = 0.028). Median Overall Survival (OS) was not reached for the entire cohort, with 1 year survival being 81.2%. Patients with an ECOG Performance Status (PS) of >2 had a significantly reduced PFS compared to patients with PS < = 2 (1.5 months vs. 11 months, p< 0.001). 47 patients with financial constraints (68.1%) received Crizotinib completely free via various extramural support schemes. Conclusion A majority of our ALK positive NSCLC patients were exposed to Crizotinib through the help of various support mechanisms and these patients had similar outcomes to that reported from previously published literature.

Relative value of ultrasound, computed tomography and positron emission tomography imaging in the clinically node-negative neck in oral cancer.

Abstract: Aim To determine the most accurate noninvasive imaging modality for occult metastasis in clinically node-negative necks in oral squamous cell carcinoma from a granulomatous disease endemic region. Method Prospective, observational study comparing ultrasound (US), contrast enhanced computed tomography (CECT) and positron emission tomography-computed tomography (PET-CT). Level wise assessment of neck nodes with each imaging modality was performed and compared with final histopathology. Results Eighty-five necks were evaluated in 70 patients. Sensitivity, specificity and accuracy of the three modalities were 78.9, 68.75 and 73.25% for US, 73.6, 85.4 and 80.2% for CECT, and 81.5, 54.1 and 66.2% for PET-CT, respectively. CECT performed better than US and PET-CT scan particularly in levels IB and II (accuracy of 81.4 and 88.3% for CECT, 73.25 and 79.1% for US, and 68.6 and 68.6% for PET-CT scan, respectively). Concordance with histology was best with CECT (κ = 0.615) followed by US (κ = 0.461) and PET-CT (κ = 0.337). Conclusion The quest for the most accurate imaging modality in clinically node-negative necks continues. US alone is inadequate. While PET-CT may not be a specific imaging modality in detecting occult cervical nodal metastasis in endemic regions of chronic granulomatous diseases, the performance of PET CECT in this setting remains to be evaluated. CECT scan, routinely used in imaging for primary disease, is fairly accurate in detecting nodal metastasis. However, in early oral cancers that are generally treated without any imaging for the primary tumor, management of the neck will largely depend on clinical judgment.

Breakdown of Bragg–Gray behaviour for low-density detectors under electronic disequilibrium conditions in small megavoltage photon fields

Abstract: In small photon fields ionisation chambers can exhibit large deviations from Bragg-Gray behaviour; the EGSnrc Monte Carlo (MC) code system has been employed to investigate this 'Bragg-Gray breakdown'. The total electron (+positron) fluence in small water and air cavities in a water phantom has been computed for a full linac beam model as well as for a point source spectrum for 6 MV and 15 MV qualities for field sizes from 0.25 × 0.25 cm(2) to 10 × 10 cm(2). A water-to-air perturbation factor has been derived as the ratio of total electron (+positron) fluence, integrated over all energies, in a tiny water volume to that in a 'PinPoint 3D-chamber-like' air cavity; for the 0.25 × 0.25 cm(2) field size the perturbation factors are 1.323 and 2.139 for 6 MV and 15 MV full linac geometries respectively. For the 15 MV full linac geometry for field sizes of 1 × 1 cm(2) and smaller not only the absolute magnitude but also the 'shape' of the total electron fluence spectrum in the air cavity is significantly different to that in the water 'cavity'. The physics of this 'Bragg-Gray breakdown' is fully explained, making reference to the Fano theorem. For the 15 MV full linac geometry in the 0.25 × 0.25 cm(2) field the directly computed MC dose ratio, water-to-air, differs by 5% from the product of the Spencer-Attix stopping-power ratio (SPR) and the perturbation factor; this 'difference' is explained by the difference in the shapes of the fluence spectra and is also formulated theoretically. We show that the dimensions of an air-cavity with a perturbation factor within 5% of unity would have to be impractically small in these highly non-equilibrium photon fields. In contrast the dose to water in a 0.25 × 0.25 cm(2) field derived by multiplying the dose in the single-crystal diamond dosimeter (SCDDo) by the Spencer-Attix ratio is within 2.9% of the dose computed directly in the water voxel for full linac geometry at both 6 and 15 MV, thereby demonstrating that this detector exhibits quasi Bragg-Gray behaviour over a wide range of field sizes and beam qualities.

Application of the polymerase chain reaction on formalin-fixed, paraffin-embedded tissue in the recognition of tuberculous osteomyelitis

Abstract: A retrospective series of 45 cases of chronic osteomyelitis collected over a period of 14 years was histologically classified into tuberculous osteomyelitis (25) and chronic non-granulomatous osteomyelitis (20). The tuberculous osteomyelitis group was divided into three subgroups: a) typical granulomas (13 cases); b) ill-defined granulomas (seven cases), and c) suspected granulomas (five cases). An in-house polymerase chain reaction amplifying the 245 bp nucleotide sequence, and capable of detecting 10 fg of DNA of Mycobacterium tuberculosis, was used on the DNA extracted from the paraffin blocks. The polymerase chain reaction was positive in 72% of cases (18) of tuberculous osteomyelitis, but when typical cases of tuberculous osteomyelitis with confirmed granulomas were considered (13), this increased to 84.6% (11). The chronic non-granulomatous osteomyelitis group gave positive polymerase chain reaction results in 20% of the cases (4). Our preliminary study on tuberculous osteomyelitis shows that the polymerase chain reaction can be a very useful diagnostic tool, since a good correlation was seen between typical granulomas and polymerase chain reaction with a sensitivity of 84.6% and a specificity of 80%. In addition, our study shows that tuberculous osteomyelitis can be diagnosed in formalin-fixed paraffin-embedded tissues in the absence of typical granulomas.

Histopathological, immunohistochemical and molecular cytogenetic analysis of 21 spindle cell/sclerosing rhabdomyosarcomas.

Abstract: Recently, spindle cell/sclerosing rhabdomyosarcoma (RMS) has been recognized as another distinct variant of a RMS. We evaluated clinicopathological features of 21 cases of spindle cell and sclerosing RMS and performed fluorescent in situ hybridization (FISH) testing in 10 (47.6%) tumours. Twenty-one tumours occurred in 16 males and 5 females (mean age, 19.7 years); commonly in the head and neck region (8) (38%) and extremities (7) (33.3%), followed by paratesticular region (2) (9.5%), chest wall (1), abdomen (1), pelvis (1) and paraspinal region (1). Average tumour size was 7.9 cm. Histopathologically, tumours that were spindle cell type (8) (38%) mostly occurred in the head and neck region, while sclerosing type (10) (47.6%) mostly occurred in the extremities. Remaining three (14.2%) tumours were mixed (sclerosing with spindle cell type). Tumour areas resembling embryonal RMS (ERMS) and alveolar RMS (ARMS) were noted in eight and three tumours respectively. Immunohistochemically, tumour cells were positive for desmin (21/21) (100%), MyoD1 (19/19) (100%), myogenin (13/15) (86.6%), SMA (2/3) and MIC2 (1/8) (12.5%). On FISH testing, none of the 10 tumours exhibited RMS1 (PAX3-FOXO1) or RMS 2 (PAX7-FOXO1) fusion. Eighteen patients underwent surgical resection and were offered adjuvant chemotherapy (CT) (4 cases), adjuvant CT + radiotherapy (RT) (4 cases) and adjuvant RT (1 case). Two patients underwent CT and a single patient received CT + RT. On follow-up (16 cases) (2-36 months), six tumours recurred and nine metastasized. Spindle/sclerosing RMSs are aggressive tumours and occur commonly in the head and neck and extremity sites. These tumours are histopathologically interrelated. Their immunohistochemical and cytogenetic profile is closer to ERMS than ARMS.