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   Table of Contents - Current issue
October-December 2019
Volume 8 | Issue 4
Page Nos. 203-260

Online since Wednesday, October 23, 2019

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Droplet digital polymerase chain reaction offers an improvisation over conventional immunohistochemistry and fluorescent in situ hybridization for ascertaining Her2 status of breast cancer p. 203
Moushumi Suryavanshi, Jiten Jaipuria, Anurag Mehta, Dushyant Kumar, Manoj Kumar Panigrahi, Haristuti Verma, Mumtaz Saifi, Sanjeev Sharma, Simran Tandon, Dinesh Chandra Doval, Bhudev C Das
Background: Droplet digital polymerase chain reaction (DDPCR) is a recent modality for detecting Her2 expression which is quantitative, cheaper, easier to standardize, and free from interobserver variation. Purpose: The purpose of this study is to incorporate DDPCR in the current diagnostic paradigm with clinical benefit. Materials and Methods: Fifty-four consecutive patients were tested by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and DDPCR. With FISH result as gold standard, receiver operating characteristic curves for DDPCR ratio were analyzed to label Her2-negative, equivocal, and positive cases as DDPCR score 1, 2, and 3, respectively. Proportion of patients labeled unequivocally as Her2 positive or negative was defined to have “clinically benefitted” from the test. Drawing parallel to inter-relationships between DDPCR, IHC, and FISH in the test cohort, four diagnostic pathways were defined – (1) initial IHC followed by FISH, (2) initial DDPCR followed by FISH, (3) initial IHC followed by DDPCR followed by FISH, and (4) initial DDPCR followed by IHC followed by FISH. Results: Clinical benefit of DDPCR as an initial test in the test cohort was 57%, while it was 65% if used as a second-line test among those with an initial inconclusive IHC result. Sensitivity analysis in the simulation cohort revealed that if DDPCR cost was ≤0.6 times the cost of IHC, then a three-step pathway with DDPCR upfront would near certainly prove most cost beneficial. If DDPCR cost was >0.6 but ≤2 times the cost of IHC, then a three-step pathway with DDPCR as second-line test had a higher probability to prove most cost beneficial. If DDPCR cost was >2 times the cost of IHC, then conventional pathway had a higher probability to prove most cost-effective. Conclusion: Incorporating DDPCR in the current clinical diagnostic paradigm has the potential to improve its cost-effectiveness and benefit.
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The evolving role of pathologic complete response in breast cancer p. 210
Nisha Hariharan, T Subramanyeshwar Rao
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Use of lorlatinib subsequent to crizotinib in anaplastic lymphoma kinase-positive non-small cell lung cancer: Indian experience p. 211
Vikas T Talreja, Vanita Noronha, Amit Joshi, Vijay Patil, Abhishek Mahajan, Kumar Prabhash
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Organochlorine pesticide exposure as a risk factor for breast cancer in young Indian women: A case–control study p. 212
Navneet Kaur, Srikant K Swain, Basudev D Banerjee, Tusha Sharma, Thammineni Krishnalata
Background: Incidence rates of breast cancer are showing an increasing trend in young women (≤40 years) in India. Risk for breast cancer in this age group can be attributed only partially to various known risk factors. Environmental exposure to organochlorine (OC) compounds has been identified as a potential risk factor. However, the possible role of OC compounds in increasing breast cancer risk in young women has not been explored. This case–control study was planned with the objectives to assess the serum levels of OC compound in a North Indian population of young women. Materials and Methods: Forty-two patients of breast cancer ≤ 40 years age and 42 age-matched controls were evaluated for exposure to OC compounds by performing assays in blood samples for pesticides such as dichlorodiphenyltrichloroethane (DDT) and its metabolites DDD and DDE; dieldrin; aldrin; methoxychlor, heptachlor; α-endosulfan; β-endosulfan; and hexachlorocyclohexane and its isomers (α, β, and γ). Results: Young women with breast cancer were found to have significantly higher serum levels of all the OC compounds except aldrin, p, p' DDT, and methoxychlor. Conclusions: Exposure to OC pesticides could be an important modifiable risk factor for breast cancer, especially in younger women.
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Cancer trends in Eastern India: Retrospective hospital-based cancer registry data analysis p. 215
Avinash Pandey, Shraddha Raj, Richa Madhawi, Seema Devi, Rajesh Kumar Singh
Background: Trends of cancer cases vary across several hospital-based cancer registries (HBCRs). There is a paucity of demographic data to evaluate trends of cancer in Eastern India. Aim: The aim of this study is to evaluate trends and pattern of cancer cases with respect to time from HBCR from Bihar. Objectives: The objective of this study is to evaluate the numbers of consecutive patients registered with eight most common type of cancer in our HBCR in Regional Cancer Centre, Bihar, and to evaluate trends of cancer cases registered with respect to time. Materials and Methods: Demographic profile of consecutive cancer patients registered from January 2014 to December 2016 (3 years) in HBCR was obtained. Patients diagnosed with common malignancies including head-and-neck cancer, gallbladder, breast, cervix, ovary, esophagus, stomach, hematolymphoid, and colorectal were analyzed. Frequency distribution, crosstabs, and line diagram were used to evaluate the trends of these common cancers with respect to time. Results: Sixty-six thousand and twenty-nine consecutive patients were registered between 2014 and 2016. Carcinoma gallbladder was the most common malignancy (21%), followed by head-and-neck cancer (19%) and breast cancer (15%). Median age at the diagnosis was 55 years for carcinoma gallbladder while 53 years and 46 years for head-and-neck and breast cancer, respectively. Male-to-female ratio was 0.6 for carcinoma gallbladder and 1.8 for head-and-neck cancer. A number of gallbladder and head-and-neck cancer registered increased by 36% (between 2014 and 2015) and 5% (between 2015 and 2016) and 24% (between 2014 and 2015) and 4% (between 2015 and 2016), respectively. Carcinoma breast and cervix showed decreasing trend with fall in registration up to 13% (between 2015 and 2016) and 27% (between 2015 and 2016), respectively. Conclusion: Carcinoma gallbladder is the most common cancer in Bihar. Head-and-neck cancer and carcinoma gallbladder are increasing while breast and cervical cancers are decreasing with respect to time.
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Performance of colposcopic scoring by modified International Federation of Cervical Pathology and Colposcopy terminology for diagnosing cervical intraepithelial neoplasia in a low-resource setting p. 218
Prabhakaran Nair Rema, Aleyamma Mathew, Shaji Thomas
Introduction: Colposcopy is a tool to evaluate women with cervical pre-cancer and cancer. To interpret the colposcopic findings, various scoring systems are used but with inter observer variations. To improve the quality of colposcopy, International Federation of Cervical Pathology and Colposcopy (IFCPC) has introduced a colposcopic nomenclature in 2011. Colposcopic scoring helps to select patients who need treatment for cervical intraepithelial neoplasia. Aim of the Study: The study aimed to evaluate the agreement between colposcopic diagnosis with the modified IFCPC terminology and cervical pathology in patients with abnormal screening tests and to assess the utility of this colposcopic scoring system in low resource settings. Methodology: Patients with abnormal screening tests who underwent colposcopic assessment in the department of Gynaecological oncology were included in the study. Colposcopic scoring was done by the modified IFCPC nomenclature. The results were compared with cytology and the final histopathology. Results: 56 patients were included in the study. The colposcopic scoring when compared to histopathology showed agreement in 65.7% which indicated the agreement was substantial and was statistically significant (P = 0.0001). With cytology the colposcopic score showed agreement in 35.6% indicating a fair agreement and this was also statistically significant (P = 0.001). Conclusion: Colposcopic scoring by modified IFCPC 2011 criteria showed substantial agreement with cervical histopathology. Compared to traditional methods, 2011 international terminology of colposcopy could improve colposcopic accuracy.
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Barriers and explanatory mechanisms in diagnostic delay in four cancers – A health-care disparity? p. 221
Abhishek Basu, Debjit Ghosh, Bidyut Mandal, Pratyusha Mukherjee, Avik Maji
Introduction: Most cancer disparities research has traditionally focused on two key outcomes, access to appropriate treatment and survival, but they do not encompass important aspects of patient-centered care such as the timeliness of diagnosis and treatment. Prolonged time intervals between symptom onset and treatment initiation increase the risk of poorer clinical outcomes and are associated with worse patient experience of subsequent cancer care. This study aims to assess the delay from symptom onset to the start of definitive treatment and to identify the possible contributory factors and its impact on response in cancers of head and neck, breast, cervix, and lung. Materials and Methods: This was a retrospective study of patients enrolled between 2015 and 2017. A questionnaire was filled in about socioeconomic aspects, patient history, tumor data, professionals who evaluated the patients, and the respective time delays. Statistical test included Mann–Whitney U test, univariate and multivariate test, and one-way ANOVA to evaluate the correlations. Results: Stage migration was significant with patient delay (P < 0.01). In head and neck squamous cell carcinoma (HNSCC) and Carcinoma lung, a significant correlation was found between referral delay and residence (P < 0.01) and treatment delay and reason for referral (HNSCC only) (P = 0.04). Referral delay and treatment delay were correlated to response in breast and cervix, respectively (P < 0.01). Conclusion: Social awareness, regularly updating primary care physicians about alarming symptoms of cancer, developing guidelines to identify these symptoms, promoting continuity of care, and enabling access to specialist expertise through prompt referral should all help prevent delays in cancer diagnosis.
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Tamoxifen and fulvestrant induced steatohepatitis with cirrhosis: A rare case report p. 225
Somnath Roy, Jaya Ghosh, Nitin Shetty, Munita Bal Menon, Anant Ramaswamy, Sudeep Gupta
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Usefulness of narrow-band imaging in transurethral resection of bladder tumor: Early experience from a tertiary center in India p. 226
Kanuj Malik, Anand Raja, Sivakumar Mahalingam, LS Ravishankar
Background: The current standard for diagnosis and treatment of urinary bladder cancer is transurethral resection of bladder tumor (TURBT) using white light guidance. Narrow band imaging (NBI) has emerged as a promising method for identifying additional bladder lesions. Various studies have been published to evaluate its sensitivity in identifying new lesions and its impact on decreasing recurrences. In this study, we evaluated our early experience using NBI in TURBTs. Aims and Objective: The aim of the study is to determine the accuracy of NBI in identifying additional malignant lesions during TURBT. Materials and Methods: We retrospectively collected data for all patients who underwent either TURBT or repeat TURBT with white light and NBI from November 2016 to July 2017 at Cancer Institute (WIA). The number of additional lesions identified using NBI was evaluated along with its correlation with the final histopathology. Results: Forty patients were analysed of which 20 underwent TURBT and 20 underwent repeat TURBT. Of these, 36 patients had complete resection of tumour. Additional lesions were detected in 6 patients (14%) by NBI of which 2 (33%) were malignant histology. The additional lesions detected were carcinoma in situ and no patient was upstaged. Conclusion: The inclusion of NBI to conventional white light TURBT increases the sensitivity for identifying additional lesions. The limitation of NBI is high false positivity and its availability. Long term follow up studies with larger subset of patients are required to evaluate its role in decreasing recurrences and justification in routine clinical practice.
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Late toxicities among laryngopharyngeal cancers patients treated with different schedules of concurrent chemoradiation at a rural tertiary cancer care center p. 229
Geetha Muttath, NV Vinin, Kalpita Shringarpure, Joneetha Jones, Satheesan Balasubramanian, Sajithbabu Thavarool, Shilpa Ajaykumar
Background: Concurrent chemoradiation is the treatment of choice for laryngeal-pharyngeal cancers. Apart from survival organ preservation remains major aims of the treatment. Advanced radiation techniques like VMAT have shown to reduce morbidity. The purpose of our study is to assess the late toxicities in patients treated with concurrent chemoradiation and its association with dose to organs at risk. Aims: Assessment of late toxicities following concurrent chemoradiation in patients with laryngopharyngeal cancers. Materials and Methods: Retrospective study at a tertiary cancer centre on patients with laryngeal and pharyngeal cancers treated with concurrent chemoradiation with VMAT upto a total dose of 69.3 -70 Gy in 33-35 fractions and concurrent chemotherapy with Cisplatin was done. Severe late toxicities and its association with demographic and clinical parameters and dose to OAR were studied. Data was analysed using EpiData analysis v2.2.2.182. Results: Of the 93 patients studied majority were males above 55 years. Oropharynx was the commonest site (58%) with T3 and N2 in majority. Late dysphagia and odynophagia was seen in 18(21%) and 23(27%) patients respectively. 16 (17%) had tube dependence and nine (9.6%) had aspiration pneumonia. D60, V50 and V60 along with site , node positivity and weight loss were found to be significantly associated with severe late toxicity. Conclusion: Oropharyngeal cancers, node positivity and weight loss were found to have significant grade III and above toxicities including tube dependency. Dose to larynx showed association with severe late toxicities, though dose to constrictors could not.
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A meta-analysis on efficacy of auto fluorescence in detecting the early dysplastic changes of oral cavity p. 233
Nallan C. S K. Chaitanya, Sunanda Chavva, Elizabeth Surekha, Vedula Priyanka, Mule Akhila, Hari Kiran Ponnuru, Charan Kumar Reddy
Background: Light-based detection agents using autofluorescence may be helpful in the detection of early dysplasia, which would otherwise be misdiagnosed as nondysplastic by conventional oral examination (COE) with white light. Visually-enhanced lesion scope (VELscope) is one of such an aid used for the purpose. A meta-analysis was carried out on the sensitivity and specificity of VELscope that would enable in providing evidence of its usage in oral dysplasia. Materials and Methods: MeSH terms such as auto florescence in oral dysplasia, VELscope, Oral ID, Identifi, in a different medical database such as PubMed, Cochrane, EBSCO, and Google scholar was carried out by four research associates. The total articles available were 242, of which, 230 were excluded based on strict criteria of randomized control trials and proper design. Finally, only 12 studies were chosen for the present analysis. Of 1643 patients from 12 studies, 1264 patients had undergone the autofluorescence examination after the COE. Only 774 patients have shown the loss of fluorescence with VELScope examination and 487 had retained the fluorescence. Biopsy was performed on 1176 patients after the autofluorescence examination in the areas where there was the loss of fluorescence. The available data were subjected to software Review Manager for analysis. Results and Discussion: Of the 11 studies analyzed, majority of them showed that the autofluorescence device were sensitive enough > 0.70; however, the values of sensitivity and specificities varied significantly. With the VELscope the diagnostic performance of the inexpert examiner was not improved, obtaining a sensitivity of 0.40 (95% of confidence interval [CI]: 0.406–0.773) and a specificity of 0.80 (95% CI: 0.614–0.923). Conclusion: The new technique may help as an adjunct to histopathology in detecting the dysplasia initially and stop further progression to the carcinoma.
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Head-and-neck paragangliomas: An overview of 54 cases operated at a tertiary care center p. 237
Shuchita Singh, Renu Madan, Manoj Kumar Singh, Alok Thakar, Suresh Chandra Sharma
Background: Head-and-neck paragangliomas (HNP's) are rare autonomic neoplasms associated with high morbidity and mortality. We aimed to study epidemiology, clinicopathological correlation, and management of HNP to assist clinicians in advocating the most appropriate therapy. Materials and Methods: Epidemiological parameters, including age and sex distribution, clinical presentation, tumor classification, familial predisposition, multicentricity, and treatment modalities adopted, were analyzed in this retrospective analysis of 54 patients of HNP. Results: Age ranged from 15 to 85 years, with a female preponderance. Among all HNP, carotid body tumor (CBT) (48.1%) was the most common, followed by Glomus Jugulare (24.1%). Majority of the patients presented with neck swelling associated with nerve palsies. A preoperative neurological deficit was most commonly observed with Glomus jugulotympanicum (68.4%). Conclusion: CBT is the largest and most common paraganglioma in our study. The familial occurrence warrants meticulous screening for multifocality. Tumor location, neurovascular involvement, malignant potential, and patient factors should guide the designing of management options.
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Metachronous muscle metastasis in a case of metastatic gallbladder cancer with TP35 gene mutation: A rare case report p. 240
Joydeep Ghosh, Sandip Ganguly, Deepak Dabkara, Bivas Biswas, Arghya Chatterjee, Sumit Mukhopadhyay, Aditi Chandra, Saugata Sen, Debdeep Dey
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Clinico-epidemiological features and response in childhood acute lymphoblastic leukemia at regional cancer center of Northeast India p. 241
Bhargab Jyoti Saikia, Partha Sarathi Roy, Gaurav Kumar, Rakesh Kumar Mishra, Anupam Sarma
Introduction: Acute lymphoblastic leukemia (ALL) comprises 19.3% of all childhood cancers in Northeast India. Methods: We analyzed clinicoepidemiological features and early response to the treatment of all the cases of childhood ALL (age <15 years) diagnosed and treated at Dr. B Borooah Cancer Institute over 1 year. Results: Of 52 eligible cases, 69% were male (male:female ratio of 2.2:1) and the mean age was 7.1 years. Thirty-three children (63%) had baseline white blood cell count ≥20 × 109/L. Precursor B-cell was most the common subtype seen in 61% of children. Seven cases (14%) had high-risk (HR) cytogenetics, with t (9,22) being the most common one. Male sex and HR cytogenetics were significantly associated with poor early responses. Conclusion: ALL is a common childhood malignancy with high cure rates. However, poor socioeconomic status and the presence of higher proportions of disease-related factors lead to poor outcome in this part of the country.
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Hyperprogression after immunotherapy Highly accessed article p. 244
Waseem Abbas, Ranga Raju Rao, Swati Popli
Introduction: Checkpoint inhibitors demonstrate very good anticancer effects, and some patients are long-time responders. As our experience to use these drugs increases, we see more and more patients having different kind of side effects which are usually not seen with chemotherapy. We have observed a subset of patients who appear to be “hyper-progressors,” with a greatly accelerated rate of tumor growth and clinical deterioration compared to pretherapy, which was also recently reported by Institut Gustave Roussy. Materials and Methods: Medical records from all patients (N = 50) prospectively treated in our hospital by anti-PD-1/PD-L1 were analyzed. The tumor growth rate (TGR) prior (“REFERENCE;” REF) and upon (“EXPERIMENTAL”; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR and overall survival (OS) were computed. Results: Hyperprogressive disease (HPD) was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 50 evaluable patients, four patients (8%) were considered as having HPD. At progression, patients with HPD had a higher rate of new lesions. HPD was associated with a worse outcome (OS). Conclusion: Hyperprogression was seen in 4 of 50 (8%) of patients, three of which had urothelial cancer and one malignant melanoma, treated with anti-PD-1 or anti-PD-L1 monotherapy. Patients, on immunotherapy, qualifying for hyperprogression had shorted OS. It is important to have a better understanding of hyperprogression on immunotherapy which shall be addressed in the ongoing immunotherapy studies.
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Detection of clinically relevant epidermal growth factor receptor pathway mutations in circulating cell-free tumor DNA using next generation sequencing in squamous cell carcinoma lung p. 247
Kanakasetty Babu Govind, Deepak Koppaka, Lokanatha Dasappa, Linu Abraham Jacob, Suresh M C. Babu, N Kadabur Lokesh, Rudresha Antapura Haleshappa, LK Rajeev, Smitha Carol Saldanha, Anand Abhishek, Vikas Asati, R Chethan, Vedam Laxmi Ramprasad
Background: Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA). Materials and Methods: In this prospective observational study, patients with squamous cell carcinoma lung, either newly diagnosed or having a progressive disease on prior therapy were eligible. Cf-DNA was extracted from peripheral blood and analyzed for EGFR, KRAS, NRAS, and BRAF mutations using NGS. Results: Sixteen patients were enrolled over a period of 1 month. The mean cf-DNA quantity extracted from the plasma was 96.5 ng (range, 15–200 ng). Eight clinically relevant mutations in the EGFR pathway were identified. These include Exon 21 mutations in 4 patients, Exon 20 mutation in onepatient, complex mutations with coexisting Exon 21 and Exon18 in one patient and KRAS Exon 2 mutations in two patients. Conclusion: cf-DNA is a minimally invasive technique for detection of clinically relevant mutations in lung cancer patients. The use of novel advanced techniques such as NGS may help in detecting EGFR pathway mutations in patients with squamous cell carcinoma lung.
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Predictive biomarkers in nonsmall cell carcinoma and their clinico-pathological association p. 250
Anurag Mehta, Nayana N Sriramanakoppa, Poojan Agarwal, Gayatri Viswakarma, Smreti Vasudevan, Manoj Panigrahi, Dushyant Kumar, Mumtaz Saifi, Irfan Chowdhary, DC Doval, Moushumi Suryavanshi
Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Genome-directed therapy is less toxic, prolongs survival and provides a better quality of life. Predictive biomarker testing, therefore, has become a standard of care in advanced lung cancers. The objective of this study was to relate clinical and pathological features, including response to targeted therapy (TT) and progression-free survival (PFS) with positive driver mutation. Materials and Methods: Archival data of nonsmall cell carcinoma patients with Stage IV disease were retrieved. Those who tested positive for one of the four biomarkers (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], MET, and ROS) were included. Patient demographics and clinical features were reviewed. Tumor histomorphology was correlated with oncological drivers. Treatment response, PFS, and overall survival were studied in three subcohorts of patients who received computed tomography (CT), CT followed by TT and those who received TT in the first line. Results: A total of 900 patients underwent biomarker evaluation of which 288 tested positive. Frequency of the four biomarkers observed was 26.6% (229/860), 6.6% (51/775), 6.6% (5/75), and 5.1% (3/59) for EGFR, ALK, MET, and ROS-1, respectively. The median PFS for EGFR-mutated cohort was 12 months, whereas it was 21 months for ALK protein overexpressing cases. Patients treated with first-line tyrosine kinase inhibitors performed better compared to those who were switched from chemotherapy to TT or those who received chemotherapy alone (P < 0.05). Conclusion: Biomarker testing has improved patient outcome. Genome-directed therapy accords best PFS with an advantage of nearly 10 months over cytotoxic therapy.
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Reverse sural flap – A feasible option for oncological defects of the lower extremity, ankle, and foot: Our experience from Northeast India p. 255
Abhijit Talukdar, Jitin Yadav, Joydeep Purkayastha, Niju Pegu, Pritesh R Singh, Revanth K Kodali, Dwipen Kalita, Srinivas Bannoth
Background: Soft-tissue management around the lower third of the leg and foot presents a challenge to the surgeon. To achieve local control of tumor, additional surgical margins are required, thus creating large soft-tissue defects. The reverse sural artery flap (RSAF) is a popular option for many of these defects. Materials and Methods: This is a retrospective study of 26 patients who underwent resection of tumor around the lower leg, ankle, and foot, and reconstruction with RSAF was performed at our institute from 2012 to 2018. Results: Among the 26 studied patients, aged between 22 and 71 (mean age: 50.8) years, 5 were female and rest were male. The most common site of involvement by tumor was heel (42.3%), followed by sole (26.9%). The most common histopathological diagnosis was melanoma (61.5%), followed by squamous cell carcinoma (26.9%) and soft-tissue sarcoma (11.5%). Conclusion: The distally based sural flap is a reliable flap for the coverage of soft-tissue defects following oncological defects of the distal lower extremity and foot.
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Primary signet-ring adenocarcinoma of the lung: A rare lung tumor p. 257
Varun Rajpal, Rahul Kumar Sharma, Charul Dabral, Deepak Talwar
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Advances in soft-tissue sarcoma – There are no mistakes, onlylessons to learn! p. 258
Sameer Rastogi, Parisa Manasa, Aditi Aggarwal, Kaushal Kalra
Background: In this decade the treatment of advanced sarcoma has seen many highs and lows in terms of successful trials and failed trials. This is possible due to great collaborations, newer therapies and histology focused trials. Methods: In ASCO 2019 many sarcoma trials were presented and we chose 3 challenging clinical trials that widen our perspective on soft tissue sarcoma. We have critically analyzed the data and have discussed the implications of these trials on current practice. First trial was ANNOUNCE trial which was done to confirm the efficacy of olaratumab after its dramatic success in advanced soft tissue sarcoma in a phase 2 trial. Another trial STRASS trial, which was unique because of being first successfully conducted randomized trial addressing preoperative radiotherapy in retroperitoneal soft tissue sarcoma. Third trial was phase 2 trial SARC 028 trial exploring the role of immunotherapy in pleomorphic undifferentiated sarcoma and liposarcoma subgroup. Result: ANNOUNCE trial failed to show OS benefit in olaratumab/doxorubicin arm as compared to doxorubicin/placebo arm . Based upon this FDA has revoked the approval of olaratumab leading to nihilism and disappointment amongst oncologists. In STRASS trial failed to meet the primary end point though there was a benefit in the liposarcoma subgroup in terms of abdominal recurrence free survival. There are several reasons that this trial might have failed. First, RPSs are not homogeneous population. RPSs might behave very differently as per the histopathology ranging from well differentiated LPS to leiomyosarcoma. Since the event rate in well-differentiated liposarcoma might happen late, the median follow-up of 43 months might not be sufficient. In SARC trial ORR in pleomorphic undifferentiated sarcoma (PUS) cohort was 9/40 (22.5%), while response rates in liposarcoma cohort were 4/39 (10.2%). There was poor correlation between the response and the tumor cells' PD-L1 positivity. Simultaneously, we must not take for granted the role of pembrolizumab in PUS as the previous study (PEMBROSARC) had also showed dismal outcomes with immunotherapy. Conclusion: In this paper we discuss the intricacies of these trials and how they affect the rapidly changing landscape in advanced soft tissue sarcoma.
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