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   Table of Contents - Current issue
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July-September 2017
Volume 6 | Issue 3
Page Nos. 93-138

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REVIEW ARTICLE  

Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations Highly accessed article p. 93
Vedang Murthy, Adnan Calcuttawala, Kirti Chadha, Anil d'Cruz, Arvind Krishnamurthy, Indranil Mallick, Sudhir Nair, Tanuja Teni, Sagar Pawar, Kaustav Talapatra, Asawari Patil, Amit Bhatt, Sanjoy Chatterjee, Monali Swain, Prasad Narayanan, Nikhil Ghadyalpatil, Manish Singhal, Moni Kuriakose, Kumar Prabhash, Jaiprakash Agarwal, Purvish Parikh
DOI:10.4103/sajc.sajc_96_17  PMID:28975111
Human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) have become increasingly common in the West, but the same cannot be said about India. These cancers have a different biology and confer a better prognosis, however, its current role in the management of patients in India is not clearly defined. At the 35th Indian Cooperative Oncology Network conference held in September 2016, a panel of radiation, surgical and medical oncologists, pathologists, and basic scientists from across the country having experience in clinical research with respect to HPV in HNSCC reviewed the available literature from India. All the ideas and facts were thereafter collated in this report. Various topics of controversy in dealing with the diagnosis and management of HPV-associated HNSCC have been highlighted in this report in context to the Indian scenario. Furthermore, the prevalence of the same and its association with tobacco and high-risk sexual behavior has been touched on. Conclusively, a set of recommendations has been proposed by the panel to guide the practicing oncologists of the country while dealing with HPV-associated HNSCC.
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ORIGINAL ARTICLE: BONE AND SOFT TISSUE SARCOMAS Top

Topical vancomycin: Does it reduce surgical site infection in bone tumors? p. 99
Suman Byregowda, Ajay Puri, Ashish Gulia
DOI:10.4103/2278-330X.214572  PMID:28975112
Introduction: We retrospectively analyzed a consecutive group of patients operated for bone tumors of extremity and pelvis who received only perioperative antibiotics (Group A) against a similar group that had additional 1 g topical vancomycin sprinkled in the wound before closure (Group B). The aim was to determine if the addition of topical vancomycin decreases the incidence of deep surgical site infection (SSI). Materials and Methods: A total of 221 patients operated between January 2011 and December 2011 were analyzed in Group A and 254 patients operated between April 2012 and March 2013 were analyzed in Group B. Any patient who required operative intervention for wound discharge was considered to be infected. All patients had a 1 year follow-up to determine the incidence of SSI. Results: The overall rate of SSI was 7% (31 of 475 patients). Seventeen (8%) of Group A patients had SSI as against 14 (6 %) of Group B patients (P = 0.337). A subgroup analysis of endoprosthetic reconstructions, internal fixation implants (plates/intramedullary nails), extracorporeal radiation treated bones and strut allografts showed no difference between the two groups of patients. Conclusion: Our data suggest that the addition of topical vancomycin before wound closure in patients operated for bone tumors does not decrease the incidence of SSI. Further investigation of this technique using a case–controlled methodology with an increase in the dose of vancomycin may be warranted.
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LETTERS TO THE EDITOR Top

Testicular metastasis in Wilms' tumor p. 101
Shikha Dhal, Maitrik J Mehta, Ankita Parikh, Maitri Bhagat, Aryakumar Banidutta
DOI:10.4103/sajc.sajc_85_17  PMID:28975113
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ORIGINAL ARTICLES: BREAST CANCER Top

Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor-positive metastatic breast cancer – A retrospective pilot analysis and viewpoint p. 102
Jyoti Bajpai, Anant Ramaswamy, Arun Chandrasekharan, Surya Mishra, Tanuja Shet, Sudeep Gupta, RA Badwe
DOI:10.4103/sajc.sajc_113_17  PMID:28975114
Introduction: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. Materials and Methods: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. Results: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6%) patients and retained in 2/13 patients (15.4%). mTOR activity was absent in four patients (30.7%), weak in six patients (46.1%), and moderate in 3 patients (23.2%). Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months) than those with weak and moderate activity, respectively (P = 0.043). There was no correlation between loss of PTEN expression and PFS. Conclusions: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.
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LETTERS TO THE EDITOR Top

Primary intraosseous squamous cell carcinoma in a dentigerous cyst p. 105
Karthika Panneerselvam, Anantanarayanan Parameswaran, B Kavitha, Elavenil Panneerselvam
DOI:10.4103/2278-330X.214579  PMID:28975115
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ORIGINAL ARTICLES: BREAST CANCER Top

Breast cancer risk factor evaluation in a Western Himalayan state: A case–control study and comparison with the Western World p. 106
Purnima Thakur, Rajeev Kumar Seam, Manoj K Gupta, Manish Gupta, Mukesh Sharma, Vikas Fotedar
DOI:10.4103/sajc.sajc_157_16  PMID:28975116
Context: Breast cancer incidence is increasing rapidly in India. The lifestyle, built, genetic makeup, reproductive and breastfeeding patterns are quite different in Indian females when compared to the Western population. Generalizing the Western data to the population residing in the Himalayan region would breed inaccuracies. Aim: The aim of our study was to identify risk factors in our own population in a Western Himalayan state of Himachal Pradesh, India. Subjects and Methods: A case–control study with 377 cases of invasive breast cancer and 346 hospital-based controls was conducted for 1 year. The data were collected by interviewing the individuals during their visit to hospital using a questionnaire. The data were analyzed using standard statistical techniques using SPSS version 17 software. Results: Factors found to have strong association with invasive breast cancer on multivariate analysis are late age at first childbirth >30 years, which is the strongest risk factor associated, late age of menopause > 50 years, high socioeconomic class, and age of female above 50 years. Conclusion: In our females, age >50 years, late age of menopause (>50 years), late age at first childbirth (>30 years), and high socioeconomic status were found to be major risk factors associated with breast cancer. Several factors implicated in the Western data were not found to be significant in our study. We need to identify such aspects in reproductive and breastfeeding patterns of women and spread awareness regarding the same.
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ORIGINAL ARTICLES: GI CANCER Top

Clinical practice and outcomes in advanced gastrointestinal stromal tumor: Experience from an Indian tertiary care center p. 110
Subhadeep Bose, Anant Ramaswamy, Arvind Sahu, Omshree Shetty, Saurabh S Zanwar, Jimmy Mirani, Chaitali Nashikkar, Vikas Ostwal
DOI:10.4103/sajc.sajc_323_16  PMID:28975117
Background: Management of advanced Gastrointestinal stromal tumors (GIST) has been revolutionized with the use of Imatinib guided by mutation analysis. Data from India remains scarce. Materials and Methods: Patients with metastatic GIST who were treated at Department of Gastro-intestinal & Hepaticopancreaticobiliary Oncology Unit at Tata Memorial Hospital, Mumbai between December, 2004 and December 2015 were included in the analysis. Clinical and radiological data was retrieved from stored medical records and charts. Results: A total of 83 patients with metastatic GIST were available for analysis. Median age was 54 years with a 3:1 male predominance. Stomach was the most common site of primary with liver being the most common site of metastasis. c-Kit mutation analysis results were available for 44 patients with exon 11 mutant being the most common mutation. With a median follow up of 33 months, the 10 years estimated progression free and overall survival (OS) was 18% and 51% respectively. Overall response rate to first line imatinib was 37.6% and estimated 3 years OS to first line therapy was significantly better for Exon 11 mutated patients (p=0.016). 34 patients received second line therapy in the form of either sunitinib, pazopanib or increased dose imatinib with a clinical benefit rate of 73.5%. C-Kit mutated patients had a better median OS compared to non mutated patients. Conclusions: GIST diagnosed and treated in the Indian subcontinent appears to show improved outcomes. The importance of c-Kit mutation analysis in determining the prognosis and outcomes of patients with advanced GIST is emphasized.
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Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience p. 113
Trupti Pai, Munita Bal, Omshree Shetty, Mamta Gurav, Vikas Ostwal, Anant Ramaswamy, Mukta Ramadwar, Sangeeta Desai
DOI:10.4103/sajc.sajc_275_16  PMID:28975118
Background: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. Materials and Methods: Morphological and immunohistochemically confirmed GIST cases (n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape® and Chromas Lite. Results: KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502–503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. Interpretation and Conclusions: First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series.
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LETTERS TO THE EDITOR Top

Comparison of the applicability of Hasford score and European Treatment and Outcome Study score in Indian patients with chronic phase chronic myeloid leukemia on imatinib therapy p. 117
Neha Chopra Narang, Mrinalini Kotru, Meera Sikka, Usha Rusia
DOI:10.4103/sajc.sajc_57_17  PMID:28975119
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ORIGINAL ARTICLES: GI CANCER Top

Metastatic gastrointestinal stromal tumor: A regional cancer center experience of 44 cases p. 118
MC Suresh Babu, Tamojit Chaudhuri, K Govind Babu, KC Lakshmaiah, D Lokanatha, Linu Abraham Jacob, AH Rudresha, KN Lokesh, LK Rajeev
DOI:10.4103/sajc.sajc_290_16  PMID:28975120
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Historically, a poor prognosis for metastatic disease has been reported with systemic chemotherapy. Significant advances have been made in the last decade, since the introduction of different tyrosine kinase inhibitors (TKIs). Unfortunately, even though the TKIs have been used for a long time, there are very few published data of the experience of TKI therapy in metastatic GIST from India. Materials and Methods: Patients diagnosed with metastatic GIST from January 2005 to October 2016 at our center, who received first-line therapy with imatinib 400 mg/day, were reviewed retrospectively. Patients' profile, response to treatment, toxicity of TKI therapy, time to progression, and survival were evaluated. Results: Of the 44 metastatic GIST patients, 23 (52.2%) were males. Median age at diagnosis was 48 years. The most common presenting symptom was an abdominal pain (52%), followed by weight loss (23%). Most frequently affected metastatic site was liver (57%), followed by peritoneum (16%), and lungs (4.5%). Metastases to both liver and peritoneum were found in 10 patients (22.5%). All patients were initially treated with imatinib at a dose of 400 mg/day. Disease stabilization was documented in 21 cases (48%), and 13 patients (29%) achieved a partial response. TKI therapy was well-tolerated in most cases. Median progression-free survival (PFS) was 26 months, and estimated median survival was 48 months. Patients with lung metastases have a significantly inferior median PFS and overall survival, in comparison to patients with other metastatic sites (P < 0.05). Conclusions: Imatinib therapy was well tolerated and induced a sustained clinical benefit in more than half of the patients with metastatic GIST. Lung metastases seemed to be a poor prognostic factor in this patient population.
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ORIGINAL ARTICLES: HEAD AND NECK CANCER Top

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India p. 122
Rudresha Antapura Haleshappa, Aditi Harsh Thanky, Lakshmaiah Kuntegowdanahalli, Govind Babu Kanakasetty, Lokanatha Dasappa, Linu Jacob
DOI:10.4103/2278-330X.214578  PMID:28975121
Context: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. Settings and Design: Retrospective analysis. Materials and Methods: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. Results: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3–4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. Statistical Analysis Used: SPSS software version 20. Conclusion: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted.
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Serum alkaline phosphatase in oral squamous cell carcinoma and its association with clinicopathological characteristics p. 125
Swetha Acharya, Jyoti Kale, Pragati Rai, Venkatesh Anehosur, Kaveri Hallikeri
DOI:10.4103/2278-330X.214574  PMID:28975122
Context: Biochemical changes occur in biological fluids and tissues of different types of malignancies. Tumor markers in serum, tissue, and other body fluids during neoplastic process are of clinical value in the management of patients with cancers. Serum alkaline phosphatase (ALP) activity is potentially a useful indicator for detection of malignancies, but its status in oral squamous cell carcinoma (OSCC) is less explored. Aims: The aim of this study is to evaluate the serum level of ALP in OSCC patients and assess its relation with the clinicopathological features. Settings and Design: A total of 175 participants (145 OSCC patients and 30 healthy controls) were included in the study. One hundred and forty-five patients with OSCC who underwent treatment at our institution were included to obtain the clinicopathological data. Materials and Methods: Fasting blood ALP activity was evaluated using ALP assessment kit and biochemistry analyzer. Statistical Analysis Used: The data were analyzed by SPSS-21 software (SPSS Statistics for Windows, Version 21.0, Armonk, NY, USA), using t-test, Mann–Whitney U, and Kruskal–Wallis tests. Results: Raised ALP was seen in 24% of OSCC patients. The mean ALP in OSCC was significantly higher than the control. ALP level in patients with advanced stage was significantly higher than with early stage. The serum ALP level in OSCC patients with bone involvement (BI) by local extension of tumor was significantly higher than without BI. Conclusion: ALP showed statistically significant differences in relation to tumor stages and BI. Hence, ALP could be useful in advanced stage disease for expressing the endurance of patient and tumor expansion. Elevated ALP in OSCC patients may indicate BI.
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ORIGINAL ARTICLES: LEUKEMIA AND LYMPHOMA Top

Systemic and primary cutaneous anaplastic large cell lymphoma: Clinical features, morphological spectrum, and immunohistochemical profile p. 129
Kanwardeep Singh Kwatra, Preethi A. M. Paul, Nalini Calton, Joseph M John, James D Cotelingam
DOI:10.4103/2278-330X.214575  PMID:28975123
Background: T-cell lymphomas with anaplastic morphology typically comprise of anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL), ALK-negative ALCL (ALK- ALCL), and primary cutaneous ALCL (PC-ALCL). However, other entities such as diffuse large B-cell lymphoma, peripheral T-cell lymphoma, Hodgkin lymphoma, and undifferentiated carcinoma can also show similar anaplastic features. Aims: To study the clinical features and histological spectrum of ALCL and emphasize the role of immunohistochemistry (IHC) in their diagnosis and categorization. Setting and Design: Eight cases of ALCL diagnosed over a period of 4 years were selected for the study. Materials and Methods: Histopathological review and IHC was performed on all cases. Two ALK+ ALCL cases were tested by fluorescent in situ hybridization (FISH) for t(2;5)(p23;q35). Results: There were four cases of ALK+ ALCL and two each of ALK- ALCL and PC-ALCL. Histologically, all the subtypes showed pleomorphic and “hallmark” cells with strong CD30 expression and variable loss of T-cell antigens. One case of PC-ALCL was leukocyte common antigen (LCA) negative. Epithelial membrane antigen was positive in all the six systemic ALCL cases. Two cases tested for t(2;5)(p23;q35) by FISH were positive. Conclusions: Diagnosis of ALCL is based on recognizing the key morphological features, especially the presence of “hallmark” cells. IHC is essential for confirmation of diagnosis and excluding other malignancies with anaplastic morphology. The inclusion of CD30 in the initial IHC panel will help identify LCA negative cases and avoid misdiagnosis.
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A comparative study of bloodstream infections in acute myeloid leukemia according to different phases of treatment: Can we predict the organism? p. 132
Preetam Kalaskar, Asha Anand, Harsha Panchal, Apurva Patel, Sonia Parikh, Sandip Shah
DOI:10.4103/2278-330X.214584  PMID:28975124
Introduction: The treatment of acute myeloid leukemia (AML) consists of induction therapy with anthracyclines and cytarabine followed by two to four cycles of consolidation therapy with high-dose cytarabine after achieving remission. There have been very few studies comparing infections during induction and consolidation. We have analyzed blood cultures of patients with AML during episodes of fever occurring during induction and consolidation, for comparing the bloodstream infections in both the phases. Materials and Methods: Blood cultures of patients during febrile episodes were collected from central venous catheters and peripheral blood, both during induction and consolidation therapy of AML. Results: The study population included 52 AML patients. During induction, there were 52 episodes of fever and 25 (48%) blood cultures were positive, 15 of these blood cultures reported Gram-negative organisms, 9 reported Gram-positive organisms and 1 as yeast. During consolidation, 47 episodes of fever were recorded and blood cultures were positive in 12, of which 7 were Gram-negative, 5 were Gram-positive. Conclusion: The incidence of blood culture positive infections during therapy of AML at our center was higher. The predominant organism isolated was Gram-negative both during induction and consolidation. The incidence of blood culture positive infections had decreased by 50% during consolidation.
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ORIGINAL ARTICLE: MELANOMA AND SKIN CANCER Top

Experiences of two different modalities in the management of choroidal melanoma in the Asian Indian population p. 134
Prajna Meeralakshmi, Parag K Shah, Venkatapathy Narendran
DOI:10.4103/sajc.sajc_160_16  PMID:28975125
Background: Choroidal malignant melanoma is a rare intraocular cancer in Asian Indian population. There is a paucity of data from our population comparing iodine 125 (I-125) brachytherapy and enucleation. Aim: This study aims to compare two groups of choroidal melanoma patients treated with either I-125 brachytherapy or enucleation in the Asian Indian population. Objectives: To evaluate the long-term morbidity and mortality rates in choroidal melanoma patients treated with either I-125 brachytherapy or enucleation. Methods: It is a retrospective study involving forty four eyes, diagnosed with choroidal melanoma from May 2008 to February 2015. All were evaluated preoperatively for metastasis. Twenty-two underwent globe salvaging I-125 brachytherapy surgery whereas remaining 22 underwent globe destructive primary enucleation procedure. Results: At a mean follow-up 39 months, 2 of 22 cases (9%) died in the brachytherapy group. One was secondary to metastasis in the liver while the other case died of a natural cause. In the enucleation group also, there were two deaths (9%) secondary to metastasis. The metastasis free survival was 95% in the brachytherapy group and 91% in the enucleation group, which was not statistically significant (P = 0.3577). Kaplan–Meier survival at 3 years and 5 years was 95% and 89% for brachytherapy group and 94% and 89% for enucleation group. Conclusion: This study found no difference in the long-term survival of choroidal melanoma patients treated with either brachytherapy or enucleation in the Asian Indian eyes.
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ORIGINAL ARTICLE: SUPPORTIVE CARE Top

Pattern of occurrence and treatment outcome of second primary malignancies: A single center experience Highly accessed article p. 137
Prekshi Chaudhary, Sweety Gupta, Nitin Leekha, Ruchir Tandon, Malay Nandy, Sudarsan De
DOI:10.4103/2278-330X.214583  PMID:28975126
Background: The incidence of cancer survivors is increasing, but these individuals, unfortunately, face the risk of second primary malignancies (SPMs). This increasing incidence can be credited to increased survival rates of cancer patients, environmental factors, host factors, and genetic predispositions. Hence, vigilance on the part of the patient as well as clinician for the development of new signs and symptoms is mandatory. Aims: Retrospective analysis of the pattern of incidence and clinical outcome of patients diagnosed with SPM and to review the literature. Settings and Design: A hospital-based retrospective collection of prospective data of patients diagnosed with SPM. Materials and Methods: Thirty-six patients with histopathologically proven SPM from January 2009 to July 2015 were included in this study. Factors such as age, sex, site, stage, histology, treatment received, and outcome were recorded. Statistical Analysis Used: Basic statistical tools have been used for analyzing the data. Results and Conclusions: The likelihood of occurrence of second malignancy, either synchronous or metachronous, should always be kept in mind while evaluating a cancer patient. Appearance of new signs and symptoms during the initial evaluation as well as during follow-up should raise a suspicion, and both patient and oncologist should have a low threshold for further assessment. Early diagnosis and treatment will reduce morbidity and mortality and lead to better survival outcome.
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