Sushmita Pathy

Neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma: A pilot study

OBJECTIVE To evaluate role of dose dense neo-adjuvant chemotherapy (NACT) prior to standard concurrent chemo-radiation (CCRT) in locally advanced cervical cancer. METHODS Between June 2010 and December 2011, 28 patients (median age - 51 years, range, 35 to 67 years) with locally advanced cervical cancer received NACT using paclitaxel (60 mg/m(2)) and carboplatin (AUC-2) weekly for 6 doses. After a mean interval of 15 days (range 7-23 days), the patients then received definitive radiation and concomitant weekly infusion of cisplatin (40 mg/m(2) for 6 doses). Response to concurrent chemo-radiation and toxicity were end points. RESULTS Following NACT, 67.8% of patients responded; complete (CR) - 2(7.1%), Partial (PR) - 17 (60.7%), stable 7 (25.0%) and 2 patients (7.1%) progressed. 24 of 28 patients received CCRT; 23/24 achieved CR. 22 of 23 complete responders continue to be in CR at a median follow-up of 12 months (range, 7 to 24 months). Grade III/IV neutropenia was the main hematological toxicity seen in 28.5% and 29% of patients, respectively during NACT and CCRT. CONCLUSIONS Neoadjuvant chemotherapy with dose dense weekly paclitaxel and carboplatin followed by standard CCRT is a feasible approach and is associated with a high response rate in locally advanced cervical cancer.

Clinical presentation and survival of retinoblastoma in Indian children

Objective To study the clinical presentation and survival among Indian children with retinoblastoma (RB) and to determine factors predictive of poor outcome. Methods A retrospective review of children newly diagnosed with RB at a tertiary referral centre was undertaken. Demographic and clinical characteristics and treatment outcomes were studied. Results A total of 600 patients (unilateral 67.6%, bilateral 32.4%) was studied. 61% was boys. The median age at presentation was 29 months (18 months vs 36 months in bilateral and unilateral cases, respectively, p<0.001). leukocoria was most common (83%), followed by proptosis (17%). Tumours were intraocular in 72.3% and extraocular in 27.7% cases. In the intraocular group, 78% were advanced Group D or E disease. Metastasis to the central nervous system was noted in 15.7% of extraocular cases. A statistically significant difference was seen between intraocular and extraocular groups in the median age (24 months vs 37.5 months, p<0.001) and median lag period (2.5 months vs 7 months, p<0.001). The Kaplan-Meier survival probability was 83%, 73% and 65% at 1 year, 2 years and 5 years, respectively. On univariate analysis, age >2 years (p=0.002), lag period >6 months (p=0.004) and extraocular stage (p<0.001) were associated with poor outcome. On multivariate analysis, extraocular invasion was predictive of low survival (HR 5.04, p<0.001). Conclusions Delayed presentation is a matter of concern. Improving awareness about the early signs and creating facilities for diagnosing and treating RB at the primary and secondary levels of healthcare are required to reduce mortality and morbidity, and lead to improved outcomes that are comparable with the developed nations.

Primary orbital calcified synovial sarcoma: A case report

A 32-year-old woman presented with a progressively increasing recurrent swelling of the left eye. An orbital tumor was detected and histologically classified as a synovial sarcoma, confirmed by immunohistochemistry and electron microscopy. Isolated cases of synovial sarcoma have been reported in the retroperitoneum, mediastinum, pharynx and orofacial region. However, the orbit is an extremely rare site. The authors report a case of recurrent primary orbital calcified synovial sarcoma in a young lady treated with surgery and radiotherapy.

Comparative Evaluation of Two-dimensional Radiography and Three Dimensional Computed Tomography Based Dose-volume Parameters for High-dose-rate Intracavitary Brachytherapy of Cervical Cancer: A Prospective Study

BACKGROUND Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. MATERIALS AND METHODS Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. RESULTS Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. CONCLUSIONS Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Accelerated hypofractionated radiotherapy with concomitant chemotherapy in locally advanced squamous cell carcinoma of lung: evaluation of response, survival, toxicity and quality of life from a Phase II randomized study

OBJECTIVE To evaluate the feasibility and efficacy of accelerated hypofractionated radiation with concomitant chemotherapy (AHFx-RT-CT) in locally advanced squamous cell carcinoma (SCC) of the lung. METHODS 36 patients were enrolled in this study (CTRI/2013/11/004143). Patients in Arm A (n = 18) received neoadjuvant chemotherapy (NACT) (paclitaxel 200 mg m(-2) and carboplatin area under the curve 5) followed by external radiotherapy (60 Gy/30 fractions/6 weeks). Patients in Arm B (n = 18) received NACT as in Arm A followed by AHFx-RT (48 Gy/20 fractions/4 weeks) with concomitant chemotherapy (cisplatin 30 mg m(-2) weekly). Primary end points included comparative evaluation of overall locoregional response rates (ORRs) and progression-free survival (PFS). Secondary end points included toxicity, quality of life (QOL) and overall survival (OS). RESULTS The median follow-up duration was 15 months. The ORR at first follow-up (72.2% vs 44%, p = 0.06) and at 1 year after treatment completion (61% vs 5.5%, p = 0.04) were superior in Arm B. The median PFS (17 vs 5.36 months; p = 0.053) and OS (24.73 vs 12.33 months; p = 0.007) were also superior in Arm B. Grade ≥3 acute pharyngitis/oesophagitis was less in Arm B (p = 0.05). Improvement of emotional function, cognitive function and chest pain was observed in Arm B. CONCLUSION The study suggests that AHFx-RT-CT is feasible for locally advanced SCC of the lung with improved response rate, survival, QOL and favourable toxicity. ADVANCES IN KNOWLEDGE To the best of our knowledge, this is the first study comparing conventionally fractionated radiation with AHFx-RT-CT. Addition of low-dose weekly cisplatin as radiosensitizer may be the potential factor responsible for improved response rate, survival and favourable toxicity in the study arm despite lower biological effective dose.

High burden of metastases and poor outcome in pelvic PNET

Data on prognostic factors in pelvic PNET are minimal. We analyzed patients with pelvic PNET treated between June 2003 and November 2011 for prognostic factors. Forty‐eight (13%) of 374 patients with PNET were pelvic PNET with median age 14.5 years (range: 5–33); 31 (65%) had metastases. After median follow‐up of 20.4 months (range: 1.3–64.9), 3‐year EFS, OS, and local‐control‐rate were 13.5 ± 5.5%, 15.4 ± 9%, and 41.3 ± 14.9%, respectively. Hypoalbuminemia (≤3.4 g/dl) predicted inferior EFS and OS for both entire cohort and metastatic group. All patients with hypoalbuminemia (n = 10) had low BMI as compared to 23/38 without hypoalbuminemia (P = 0.02). Pediatr Blood Cancer 2013;60:E97–E99.

Alveolar soft part sarcoma of orbit: A rare diagnosis

OBJECTIVE Alveolar soft part sarcoma (ASPS) is an aggressive, rare tumour with unique morphological and histopathological features. METHODS We report a rare case of orbital ASPS and its management in a young male who presented with painless proptosis and progressive loss of vision. RESULT Twenty-two year male presented with a history of gradually increasing proptosis with loss of vision since 12months. He underwent radical re-excision of mass with right orbital exenteration and reconstruction using temporalis muscle flap. Adjuvant radiotherapy to a dose of 64Gy in 32 fractions over 6.5weeks was planned in view of positive surgical margins. Patient is free of disease and currently under follow up in multidisciplinary clinic. CONCLUSION Function preserving surgery remains the standard treatment approach in localised disease however the complex anatomy and locally aggressive nature makes it difficult to achieve clear surgical margin. Adjuvant radiotherapy has shown to improve local control in patients with positive surgical margins.

Radiation Therapy in Paediatric Orbital Granulocytic Sarcomas: Experience from a Tertiary Cancer Center.

INTRODUCTION Orbital Granulocytic Sarcoma (OGS) is an uncommon manifestation associated with haematological malignancies. Chemotherapy remains the cornerstone of the treatment. The role of radiation is not well-defined. AIM To evaluate the effect of radiation in OGS and to define an optimal dose for achieving adequate local control. MATERIALS AND METHODS This was a retrospective analysis of 11 patients who received radiation therapy to orbit for Granulocytic Sarcoma (GS) between 2007 and 2014 at a tertiary cancer center in India. Radiotherapy was planned by three dimensional conformal (3DCRT) techniques. Demographic and disease characteristics, including clinical, imaging, histopathology and treatment details in this patient cohort were recorded and their response to therapy was assessed. RESULTS The median age was 7 years (Range: 2-16 years). There were 3 female and 8 male patients. Eight patients were diagnosed as Acute Myelogenous Leukemia (AML), two patients had Primary Orbital Granulocytic Sarcoma (POGS) and one had bi-phenotypic leukemia. Median dose was 24.5Gy (Range-15-45 Gy). Two anterior oblique field design were used most commonly. Out of 11 patients, 5 (45.4%) had complete response, 3 (27.27%) had partial response, 1 patient had stable disease (9%) and 2 developed progressive disease (18%). Median follow-up was 24 months (Range 24-84 months). At last follow-up, 7 (63.6%) patients were alive and 4 patients (37.4%) were dead due to progressive disease. CONCLUSION In patients with residual orbital disease after chemotherapy, low dose radiation can be used to improve local disease control and improve quality of life. Local conformal radiotherapy of 24-30 Gy in conventional fractionation appears optimal with excellent local control and minimal morbidity.

Adjuvant Radiotherapy with Three-Dimensional Conformal Radiotherapy of Lacrimal Gland Adenoid Cystic Carcinoma.

BACKGROUND & AIM Adenoid cystic carcinoma (ACC) of lacrimal gland is a rare tumour with aggressive behaviour. There is sparse data to address optimum therapy for such tumours. So, the present study was aimed at evaluating the role of adjuvant three dimensional conformal radiotherapy (3D-CRT) in cases of incomplete (R1) resection along with review of literature pertaining to management of lacrimal adenoid cystic carcinoma. MATERIALS AND METHODS We retrospectively reviewed the demographic and treatment data of 10 biopsy proven ACC of lacrimal gland patients, treated from December 2006 to June 2013. They were treated with radiotherapy following surgical resection. Eight patients underwent gross total excision of the tumour mass (enbloc excision) followed by conformal radiotherapy to a dose of 60 Gray/30fractions/ 6 weeks. Two patients with advanced disease were treated with palliative radiotherapy after biopsy. RESULTS The median age was 32 years. There were equal numbers of male and female patients. The median duration of symptoms was 7 months. At a median follow up of 21 months, eight patients had no evidence of disease and had complete tumour response, two patients worsened, and one of the two had systemic failure with bone metastasis. CONCLUSION Despite a small sample size and short follow, enbloc surgical excision with adjuvant radiotherapy is well tolerated and shows good control in ACC of lacrimal gland.