Will health marketplace apps improve laboratories? Jacob McKnight, Ken Fleming Indian Journal of Cancer 2019 56(4):291-292

Revisiting adjuvant ovarian suppression in premenopausal breast cancer patients Waseem Abbas, Ranga Raju Rao Indian Journal of Cancer 2019 56(4):293-296 Adjuvant ovarian suppression, on addition to chemotherapy, reduces the risk of breast cancer in pre-menopausal women after surgery and adjuvant hormonal therapy. Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) showed greater benefit with exemestane in high risk females in comparison to Tamoxifen. Ovarian Function Suppression (OFS) and exemestane became the standard of care, with 30% patients experiencing grade 3 and more side effects. Much higher benefit was seen in high risk group. But there are concerns about incomplete OFS (estrogen escape) with exemestane plus OFS. Updated analysis of TEXT AND SOFT showed better survival benefit with OFS plus Tamoxifen as compared to OFS plus exemestane. Overall survival is a better end point. Should preference be given to Tamoxifen over exemestane? Further research is required to get the final answer.

Management of colon cancer at a tertiary referral center in India - Patterns of presentation, treatment, and survival outcomes Jarin Noronha, Ashwin deSouza, Prachi Patil, Shaesta Mehta, Reena Engineer, Vikas Ostwal, Anant Ramaswamy, Suman K Ankathi, Mukta Ramadwar, Avanish Saklani Indian Journal of Cancer 2019 56(4):297-301 AIM: To define the patterns of disease presentation, treatment strategies, and outcomes for patients with colon cancer at a tertiary referral center in India over 1 year period. MATERIALS AND METHODS: This is a retrospective analysis of a prospectively maintained database. All consecutive patients with proven or suspected colonic adenocarcinoma between July 2013 and July 2014 were evaluated in a dedicated analysed multidisciplinary clinic at the Tata Memorial Hospital, Mumbai. The demography, treatment plan, pathology, stage, and survival data were examined. RESULTS: The median age of presentation was 49 years with 60.1% male patients. In total, 151 cases (57.4%) underwent treatment with curative intent consisting of surgery with adjuvant chemotherapy as indicated. The rest were offered either palliative chemotherapy (36.9%) or best supportive care (5.7%). Approximately, 70% patients had advanced stage disease (Stage III/IV) at presentation and 41.8% presented with metastatic disease with the liver being the most common site of disease dissemination. With a median follow-up of 29 months, the estimated 3-year disease free survival for patients treated with curative intent was 67.1%. The median progression free survival was 12.3 months for patients treated with palliative intent. The estimated 3-year overall survival was 89.7%, 65.5%, and 22.8% for Stage I/II, Stage III, and Stage IV, respectively. CONCLUSION: Indian patients with colon cancer, at a tertiary referral center, tend to present at more advanced stages of the disease as compared to the West. However, curative treatment with surgery and chemotherapy offers similar survival outcomes when compared stage for stage.

Prognostic and predictive significance of microsatellite instability in stage II colorectal carcinoma: An 8-year study from a tertiary center in South India Roopa R Paulose, Divya A Ail, Shital Biradar, Anu Vasudevan, KR Sundaram Indian Journal of Cancer 2019 56(4):302-308 BACKGROUND: Microsatellite instability (MSI) accounts for 15–20% of colorectal cancer (CRC) and is considered to have favorable stage-adjusted prognosis compared to Microsatellite stable (MSS) CRCs. Determination of MSI in stage II CRC is important for management decisions regarding adjuvant chemotherapy administration. The aim of this study was to determine the prognostic and predictive significance of MSI in stage 2 CRC in the Indian scenario. MATERIALS AND METHODS: A total of 195 patients who underwent curative surgery for stage II CRC from 2010 to 2017 were included. MSI testing by immunohistochemistry (DNA MisMatch Repair proteins) was performed in all. Various clinicopathological factors and disease-free survival and overall survival were assessed between MSI and MSS groups. The effect of treatment in terms of survival benefits with adjuvant therapy in the MSI group was also assessed. RESULTS: 27.1% of the CRCs' showed MSI. Younger age (<50 years), family history of cancer, synchronous/metachronous malignancies, proximal (right sided) location, poor morphological tumour differentiation, mucin production, and presence of peritumoral (Crohn's-like) lymphocytic response showed statistically significant association with MSI. Majority (56%) of our patients showed combined loss of MLH1 and PMS2. Overall, survival among the MSI patients was significantly higher (76.6 ± 4.149 months) than the MSS patients (65.05 ± 3.555)P= 0.04. MSI patients did not show any differences in survival with or without treatment. CONCLUSION: This study highlights the distinct clinicopathological features of MSI-related CRC and the relevance of MSI testing of stage II CRC for management decisions and prognostication.

Microsatellite instability in young patients with mucinous colorectal cancers – characterization using molecular testing, immunohistochemistry, and histological features Nitty Skariah Mathews, Dipti Masih, Rohin Mittal, Benjamin Perakath, Dhananjayan Sakthi, Grace Rebekah, Rekha Pai, Anna B Pulimood Indian Journal of Cancer 2019 56(4):309-314 CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers – BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects.

An observational single-center study of nivolumab in Indian patients with recurrent advanced non-small cell lung cancer Naresh Somani, Pawan Agarwal, Harish Singhal, Abhishek K Singh, Abhilasha Sinha, Rajshri Somani, Jia Agarwal, Shaurya Dugar Indian Journal of Cancer 2019 56(4):315-319 Purpose: Limited treatment options are available for patients with advanced non-small cell lung cancer (NSCLC) after failure of first-line platinum-based chemotherapy. The treatment of recurrent advanced NSCLC progressed with the arrival of nivolumab and other immunotherapeutic agents. Our single-center prospective study aimed to present the effectiveness and safety of nivolumab in second-line setting after first-line platinum doublet in Indian patients with advanced NSCLC. Patients and Methods: Twenty-nine adult patients with stage IV NSCLC treated with nivolumab after failure of first-line platinum-based chemotherapy at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, India, between October 2016 and January 2018, were included in the study. Overall survival (OS), hematological, and nonhematological toxicities were evaluated. Results: A total of 29 patients (mean age of 59.6 years at enrollment) were evaluated. Histological evaluation revealed adenocarcinoma (44.8%) and squamous (55.2%) type of cancer. The Eastern Cooperative Oncology Group performance score was II in 7 patients (24.1%) and I in 22 (75.9%) patients. Patients received an average of four cycles of nivolumab. The median survival duration was 101 days, and OS rate in the study was 51.7%. Six patients (20.7%) had stable disease response, five patients (17.2%) had partial response, and three patients (10.3%) were lost to follow-up. Asthenia and cough were the most common nonhematological toxicities. Only three patients developed hematological toxicities (anemia and thrombocytopenia). Conclusion: Data from our study suggest nivolumab is well-tolerated and effective in Indian patients with recurrent advanced NSCLC after failure of the multiple first lines of platinum-based combination chemotherapy.

Higher incidence of syndrome of inappropriate antidiuretic hormone secretion during induction chemotherapy of acute lymphoblastic leukemia in indian children Shwetha Seetharam, Priyakumari Thankamony, Kaduveettil Gopinathan Gopakumar, K M Jagathnath Krishna Indian Journal of Cancer 2019 56(4):320-324 BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known adverse effect of vincristine (VCR). Literature suggests that Asians are predisposed to develop SIADH following VCR administration. However, data regarding the occurrence of SIADH in children with malignancy are limited. This study aims to analyze the incidence, clinical picture, risk factors, management, and outcome of SIADH during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A prospective study was conducted among the 166 newly diagnosed pediatric ALL patients who were treated at a tertiary cancer center in India between January 2015 and December 2015. Patients who developed hyponatremia during induction chemotherapy were further investigated for SIADH. RESULTS: The incidence of SIADH was 10.8% (n = 18) with a mean sodium level of 125 mEq/L (114–129 mEq/L). In the preceding 2 weeks, 72% of episodes were associated with the administration of two (n = 6) or three (n = 7) doses of VCR. One child presented with seizures. All the patients were managed with fluid restriction and only two patients required sodium correction with 3% saline. Girls older than 10 years of age showed a marginally significant correlation to develop SIADH (P-value = 0.059). CONCLUSION: We report a higher incidence of SIADH (10.8%) in Indian children, compared to that described in the literature, during induction chemotherapy for ALL. Regular monitoring of sodium levels during this period of chemotherapy is hence essential for the timely diagnosis and appropriate management of SIADH, which in turn will avert complications, including neurological symptoms secondary to SIADH.

Unusual loco-regional presentation in papillary carcinoma of thyroid: A case series Prateek V Jain, Rajeev Sharan, Kapila Manikantan, Gautam Biswas, Soumendranath Ray, Pattatheyil Arun Indian Journal of Cancer 2019 56(4):325-329 BACKGROUND: Papillary carcinoma of thyroid (PTC) is usually indolent with good prognosis and excellent long-term survival. However, PTC sometimes presents itself in unusual situations, posing diagnostic and therapeutic challenges. Owing to paucity of data, there is lack of consensus as to what treatment should be prescribed in patients with loco-regional spread other than the usual sites. MATERIALS AND METHODS: Six patients of PTC presenting with involvement of the aero-digestive tract, retropharyngeal, and para-pharyngeal lymph nodes and great vessels of the neck are included in this case series. RESULTS AND CONCLUSION: Though rare, unusual loco-regional presentation of PTC poses challenges in diagnosis and treatment. A keen clinical sense is paramount in effectively diagnosing these cases. Aggressive surgical resection and reconstruction results in good functional and aesthetic outcomes. Further studies are required for establishing specific guidelines on the approach to the treatment of these cases.

Biological tailoring of adjuvant radiotherapy in head and neck and oral malignancies – The potential role of p53 and eIF4E as predictive parameters Bindhu Joseph, Rekha V Kumar, G Champaka, Ashok Shenoy, KS Sabitha, V Lokesh, C Ramesh, CR Vijay Indian Journal of Cancer 2019 56(4):330-334 BACKGROUND: Recent advances in radiation technology has allowed to significantly reduce toxicity and improve the efficacy of radical radiotherapy in head and neck and oral squamous cell cancers. Insights into molecular biology of carcinogenesis has opened a window for identifying aggressive clinical situations that may benefit with larger clinical target volume (CTV ) margin, broader levels of nodal coverage, or alternative radiation sensitizers. AIM: To evaluate the potential role of eukaryotic translation initiation factor 4E (elF4E) and p53 as predictive biomarkers in resected margins of head and neck and oral cancers. MATERIAL AND METHODS: Forty patients with oral cancers and 26 patients with head and neck cancers were evaluated for p53 and eIF4E in their negative surgical margins, for pattern of distribution and outcome. RESULTS: In oral cancers, 27 patients (67.5%) were positive for p53 and 10 (25%) for eIF4E in surgically negative margins. For head and neck cancer, the values were 13 (50%) for p53 and 9 (34.6%) for eIF4E. Twelve patients with oral cancers and 8 patients with head and neck cancers had local failure or death. The association with these biomarkers did not achieve statistical significance. However, adjuvant radiotherapy had a significant protective value. It improved median survival from 15 to 21 months in patients positive for p53 (P = 0.018) and from 12 to 20 months (P = 0.03) in those with eIF4E. There was no predictive association of subsite, tumor size, or nodal status. CONCLUSION: The overexpression of p53 and eIF4E in pathologically negative margins may represent a subset of patients who would benefit from early initiation of adjuvant radiation and tailored intensity-modulated radiotherapy (IMRT).

Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India Anuj Verma, Santosh Menon, Bharat Rekhi, Trupti Pai, Amita Maheshwari, Jaya Ghosh, Sudeep Gupta, Kedar Deodhar Indian Journal of Cancer 2019 56(4):335-340 Background: Endometrial stromal sarcoma (ESS) is a common uterine mesenchymal malignancy. According to World Health Organisation (WHO) 2014 classification, ESSs are further subdivided into low-grade ESS (LGESS) and high-grade ESS (HGESS). HGESS is defined by the presence of YWHAE gene rearrangement and has a poorer prognosis compared to LGESS. METHODS: Twenty-four cases comprising of 16 endometrial stromal sarcoma and 8 lesions mimicking ESS were retrieved from the archives of the Department of Pathology and subjected to fluorescent in situ hybridization (FISH) analysis for YWHAE gene rearrangement. Immunohistochemistry for CD10, ER, PR, Cyclin D1, SMA, H-Caldesmon, Desmin, Ki-67, and Pan Cytokeratin was performed. RESULTS: Two cases with histological features similar to HGESS were positive for YWHAE gene rearrangement while 1 was indeterminate. No cases of LGESS and histological mimics of ESS were positive for this rearrangement. CONCLUSIONS: HGESSs are defined by the presence of YWHAE rearrangement. These tumors present at higher stage and have poorer prognosis. They may not respond to hormonal therapy and may be treated with chemotherapy. Cyclin D1 though not specific remains a sensitive tool to triage endometrial stromal sarcomas for this FISH study.