Clinical Spectrum, Pattern, and Level-Wise Nodal Involvement Among Oral Squamous Cell Carcinoma Patients - Audit of 945 Oral Cancer Patient Data.

Oral Squamous cell carcinoma (OSCC) is a locoregionally aggressive malignancy. Timely management of neck node dissemination, an important prognostic factor, impacts survival. The aim of the current study was to obtain comprehensive data on patterns or level-wise involvement of neck nodes to optimize neck management in OSCC. It was a retrospective analysis of a prospectively maintained database in a hospital-based setting. The current study evaluated patterns of spread to neck nodes in 945 pathologically proven OSCC patients who underwent neck dissection between 1995 and 2013. Clinical, surgical, pathological, level-wise information of neck nodes was available, and records of these patients were analyzed in relation to the pattern of involvement. Absolute/relative frequency distribution was used to describe the distribution of categorical variables. Continuous measures were organized as mean (standard deviation) and/or median (range). Buccal mucosa (28.78%) was the most common, whereas lip (5.08%) was the least common oral subsite. Modified neck dissection (69.75%) was the most common type of neck dissection. Pathological node positivity was documented in 39.8% patients and Level I(62.54%) and level II(57.33%) are the most common neck levels for nodal involvement. Involvement of Level III to V was seen less often (7.17%). There was no significant association between node positivity among different subsites of oral cancer. Neck level I and II are the most commonly involved levels. Sensitivity and specificity of clinical assessment are 83.51% and 30.05%, respectively. In view of this void in clinical assessment and a predictable nodal spread, alternate node assessment methodology must be explored.

Genetic Polymorphism in TNF-α-308 G/A and TNF-ß +252 A/G, as Prognostic Biomarker in Breast Cancer Patients among Indian Population.

BACKGROUND: Cytokines are the key regulator molecules that modulate immune response. Tumor necrosis factor (TNF- α-308 G/A and TNF-ß +252 A/G ) are inflammatory cytokine that control the progression of several types of cancer. They play a vital role in both tumor progression and destruction based on their concentrations. The role of TNF-α-308 G/A and TNF-ß +252 A/G gene polymorphism in the etiology of breast cancer (BC) is not clearly understood. Therefore, present study investigates the association of TNF-α -308 G/A and TNF-ß +252 A/G and the clinical features with Breast cancer patients. METHODS: In a case- control study, we have investigated 150 breast cancer patients and 300 age and ethnically matched healthy controls for duration of 3 years from North India. Promoter polymorphisms of tumor necrosis factor gene (TNF-α -308 G/A and TNF-ß +252 A/G) were genotyped using allele specific oligonucleotide polymerase chain reaction ASO and restriction fragment length polymorphism (PCR-RFLP). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI) using SPSS. RESULTS: Patients with different clinico-pathological variables and healthy controls were analyzed. Significant association was observed in A allele of TNF-α -308 G/A in breast cancer patients as compared to healthy controls (p<0.0001). However, no association was seen in TNF-ß +252 A/G both at genotypic and allelic level. The GG genotype of TNF-ß +252A/G is higher in grades III (p<0.01) patients. CONCLUSION: Our results suggest that TNF-α-308G/A polymorphism showed significant association with breast cancer patients.

Multimodality management of incidentally detected gall bladder cancer: long term results from a tertiary care cancer centre.

BACKGROUND: Gall bladder cancer (GBC) is the most common biliary tract malignancy in India. GBC present either with incidental diagnosis after simple cholecystectomy (SC) or with a primary gall bladder mass. Incidentally detected gall bladder cancer (ICGB) has traditionally been thought to be a relatively early stage disease but there are controversies associated with various aspects of its management. In this article we describe our experience with multimodality management of ICGB. METHODS: A retrospective analysis of incidentally detected GBC patients was performed to analyze the profile of presentation and treatment outcome. After initial radiological evaluation for operability, all the patients underwent surgical exploration. If found resectable, revision surgery including 2 cm wedge resection of liver and lymphadenectomy was done followed by concurrent chemo-radiation for tumors T2 and above stages. RESULTS: A total of 54 patients with incidentally detected GBC with a male to female ratio of 1:3 and mean age of 47.5 years were included in the study. Thirty-four (63%) patients underwent curative resection followed by adjuvant chemoradiotherapy. The remaining 20 patients had metastatic/unresectable disease. The 5 years disease free and overall survival (OS) for patients receiving curative treatment was 64% and 72% respectively. On univariate analysis, presence of residual disease in the gallbladder fossa and liver were significant risk factors for disease recurrence. Depth of invasion, adjuvant treatment received and stage were significant prognostic factors for OS. CONCLUSIONS: Incidentally detected GBC is increasing in incidence. A multi-modality approach with revision surgery and adjuvant chemo-radiation treatment may yield better outcome. Presence of residual disease is a poor prognostic factor. Optimal evaluation before SC and early referral to specialty center is therefore important in patients with suspicion of gallbladder malignancy because first chance is probably the best chance.

Aberrant Promoter Methylation of YAP Gene and its Subsequent Downregulation in Indian Breast Cancer Patients.

BACKGROUND: YAP, a potent oncogene and major downstream effector of the mammalian Hippo tumor suppressor pathway can act as either oncogene or tumor suppressor gene based on the type of tissue involved. Despite various studies, the role and mechanism through which YAP mediates its tumor suppressor or oncogenic effects are not yet fully understood. Therefore in the present study we aimed to investigate YAP at DNA, mRNA and protein level and also attempted to correlate our molecular findings with various clinicopathological variables of the patients. METHODS: The study comprised of a total 137 genetically unrelated women with sporadic breast cancer cases and normal adjacent tissues not infiltrated with tumor. Mutation of YAP gene was analyzed by automated DNA sequencing. YAP promoter methylation was studied using MS-PCR. Expression at mRNA and protein level was studied using qPCR and IHC respectively. RESULTS: In our study YAP mRNA expression was found to be 8.65 ± 6.17 fold downregulated in 67.15% cases. The expression of YAP when analyzed at the protein level by IHC was found to be absent in 78.83% cases. Results from MS-PCR analysis showed that YAP promoter methylation plays an important role in declining the expression of YAP protein. The absence of YAP protein coincided with 86.60% methylated cases thereby showing a very strong correlation (p = 0.001). We also investigated YAP mutation at the major check point sites in the Hippo pathway and observed no mutation. A significant association was observed on correlating mRNA expression with clinical stages (p = 0.038) and protein expression with ER status (p = 0.018) among Indian breast cancer patients. CONCLUSION: The expression of YAP was found to be downregulated in response to aberrant promoter methylation. The downregulation of YAP are consistent with previous studies suggesting it to have a tumor suppressive role in breast cancer. We did not observe any mutation at the major check point sites in the Hippo pathway.

Minimizing Post-operative Complications of Groin Dissection Using Modified Skin Bridge Technique: A Single-Centre Descriptive Study Showing Post-operative and Early Oncological Outcomes.

INTRODUCTION: Historically, groin dissections are associated with high morbidity. Various modifications have been described in the literature with inconsistent outcomes. The aim of this paper is to highlight modified skin bridge technique to minimize all post-operative complications of groin dissection without compromising early oncological outcomes. METHODS: A retrospective descriptive study of the computerized cancer database was performed to retrieve details of all the cancer patients who had undergone groin dissections during January 2012 to September 2016. Data pertaining to clinical profile including demographics, clinical and histopathological details, treatment profile, procedure-related morbidity and relapse patterns were extracted and analysed. RESULTS: A total of 75 patients underwent 105 groin dissections during this period. Out of 105 groin dissections, 43 were inguinal lymph node dissection (ILND) and 62 were combined ilio-inguinal lymph node dissection (IILND). The most common diagnosis was carcinoma penis (25%) followed by malignant melanoma (14.6%) and squamous cell carcinoma (13.33%) of lower extremities. Overall, the most common complications were seroma (14.28%) and skin edge necrosis (7.61%) followed by surgical site infection (4.76%). After a median follow-up of 17.64 months (IQR 5-61.53), a total of 18 patients (24%) developed recurrence. CONCLUSION: Groin dissection still remains an important diagnostic as well as therapeutic procedure justifying its potential of morbidity. Modified skin bridge technique is a very effective method to minimize all post-operative complications with optimal early oncological outcomes.

Operable Oral Tongue Squamous Cell Cancer: 15 Years Experience at a Tertiary Care Center in North India.

The aim of the present study was to provide insight into various demographic, clinical, and management profile of Indian patients with oral tongue squamous cell cancer (OTSCC). All the OTSCC patients who had undergone surgical treatment during 1995 to 2010 at a tertiary care center in North India were considered for the present study. The details of the patients were retrieved from a prospectively maintained computerized database. A total of 124 patients were included in the present study. Mean age of the patients was 50.4 ± 12.0 years. Lateral border of the tongue was the most common sub-site involved in 110 (88.7%) patients. Neck nodes were clinically palpable in 56.4% patients. Hemiglossectomy and anterior partial glossectomy were common surgical procedure undertaken in 57.2 and 25.8% patients. Negative resection margin was achieved in 97.5% patients. Pathological neck metastasis was seen in 40.3% patients. Occult neck metastasis was present in 25.9% patients among clinical N0 neck. At a mean follow-up of 29.8 months (SD 3.1), 20.1% developed disease relapse and 4.0% patients developed second primaries. Kaplan-Meier analysis estimated a 5-year disease-free survival of 81.5% and a 5 years overall survival of 78.6%. Cox proportional regression analysis predicted tumor size and number of positive nodes to be independent predictive variables for disease recurrence. Quality controlled surgery, coupled with adjuvant treatment when required, provides a safe and effective treatment of OTSCC with a good disease-free survival and loco-regional control.

Clinical Spectrum, Treatment and Relapse Patterns in 353 Patients with Squamous Cell Carcinoma of the Alveobuccal Complex Treated with a Curative Intent: A Retrospective Study.

AIMS AND OBJECTIVES: Oral cancer is one of the most common cancers in Indian subcontinent with alveobuccal complex as most common cancer sub site. Cancers of Alveobuccal complex provides maximum challenge and management guidelines are not clear. The aim of the present study is to provide comprehensive demographic, clinical and treatment outcome data of alveobuccal squamous cell carcinoma (SCC) patients treated at a tertiary care cancer center in North India. MATERIALS AND METHODS: An analysis of prospectively maintained database in department of surgical oncology at Dr BRA-IRCH, AIIMS, Delhi, India was performed. All alveobuccal cancer patients who had undergone surgery from 1995 to 2010 were included for analysis. RESULTS: A total of 353 patients were included for analysis. Mean age was 49.75 years (SD ±12.04) with male and female ratio of 4:1. Composite resection without mandible was done in 25 % patients and 75 % underwent mandibular resection. Neck dissection was performed in 347 patients. Nodal deposits were identified in 124 (35.73 %) neck dissection specimens. Margin negative resection was performed in 89.5 % cases. After a median follow up of 30 months, 87 (24.64 %) patients developed disease relapse and 25 (7.08 %) patients developed second primaries. Overall 5-year disease free survival (DFS) was 57.65 % and 5 year overall survival (OS) was 59.86 %. CONCLUSION: Among Indian oral cancer patients alveobuccal complex is most common sub site. Majority presents in locally advanced stage and reasonably good outcomes can be achieved with quality control surgery and judicious use of radiotherapy.

Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer and accounts for 10%-15% of all breast cancers in the west. There is a scarcity of data on ILC from the Indian subcontinent. This report intends to present the patterns of care, survival outcomes, and prognostic factors of ILC treated in a tertiary care institute. MATERIALS AND METHODS: This retrospective analysis included consecutive patients diagnosed with ILC and registered at our Institute between 2009 and 2016. RESULTS: We included 97 patients with a median age of 53 years (range 28-80). American Joint Committee on Cancer (7th edition) stage distribution was stage I-8.24%, stage II-45.36%, stage III- 34.10%, and stage IV-12.30%. Bilateral breast cancer was seen in 8 cases. Estrogen receptor, progesterone receptor, and HER 2/neu positivity was 90%, 85%, and 9%, respectively. Triple-negative breast cancer constituted 5% of cases. Twenty-nine events were recorded (systemic and locoregional relapse) with a median follow-up of 3.5 years. Three years relapse-free survival (RFS) and overall survival were 80% and 60%, respectively. Bones were the most common site of metastasis. Age <45 years [HR-1.4 (0.8-2.1), P < 0.001] and advanced clinical tumor stage [T4, HR-2.1 (1.1-3.8), P = 0.001] were associated with poor RFS. CONCLUSION: ILC constituted 2.5% of breast cancer cases at our institute. Triple negativity and HER-2/neu positivity were seen in 9% and 5% of cases, respectively. Age <45 years and advanced clinical tumor stage were associated with poor RFS.

Extraskeletal orbital mesenchymal chondrosarcoma: surgical approach and mini review.

Extraskeletal orbital mesenchymal chondrosarcoma (MC) is an extremely rare and highly aggressive tumour. It has characteristic radiological features and pathognomic histological biphasic pattern. Radical resection with negative margins is the mainstay of treatment; role of adjuvant chemotherapy and radiotherapy is yet not well defined. We report a rare case of 18-year-old man who was diagnosed to have orbital MC. He presented with locally advanced disease with no vision in the affected eye. He underwent right orbital exenteration; a transcranial intradural approach was used to divide the optic nerve, and the temporalis muscle flap was utilised to fill the exenterated orbit. Though optic nerve involvement is rare in orbital MCs, a transcranial approach may be used effectively to avoid traction on optic chiasma and ensure margin-free resection in case of optic nerve involvement up to orbital apex. Unfortunately, prognosis remains dismal in MCs despite treatment.

A Comparative Study of Clinical Profile and Relapse Patterns in TRIPLE-NEGATIVE and Non-Triple-Negative Breast Cancer Patients Treated with Curative Intent.

Molecular subtyping in breast cancer is recently emerging as an important determinant of treatment and outcomes, and triple negative breast cancer (TNBC) has been established as a distinct clinical entity with unique features and adverse outcomes. A retrospective analysis of a prospectively maintained computerized breast cancer database was performed, and all the non-metastatic female breast cancer patients undergoing potentially curative multimodality treatment between 2005 and 2012 were included for analysis. Patients with incomplete information regarding ER, PR, and HER2/neu status were excluded. All the eligible patients were divided into TNBC and non-TNBC group based on molecular subtyping. A comparative analysis between the two groups was performed to analyze the clinical spectrum and patterns of relapse. A total of 861 patients qualified for the final analysis and the proportion of TNBC was 254 (29.5%) and non-TNBC was 607 (70.5%). Patients in the TNBC group were slightly younger than the non-TNBC group (median age 46 vs. 49, p value = 0.006). TNBC group had a higher breast conservation surgery (BCS) rate, and there was no difference in the need for chemo and radiotherapy between two groups. The overall recurrence rates were significantly higher in TNBC group compared to non-TNBC group (26.8 vs. 19.3%, p value = 0.01). Local disease recurrences were significantly higher in TNBC compared to non-TNBC (7.9 vs. 3.1%, p value = 0.002). Both the regional and systemic recurrences were higher in TNBC group compared to non-TNBC, though the difference failed to attain statistical significance (for regional recurrences 2.4 vs. 1.5%, p value = 0.36; for systemic recurrences 23.2 vs. 17.8%, p value = 0.06). The brain metastasis was significantly higher in TNBC group (6.7 vs. 3.3%, p value = 0.02). In addition, time to relapse was also significantly less in TNBC cohort (16.1 vs. 22.1 months). TNBC accounts for almost one-third of the breast cancer patients with a relatively younger age at presentation, higher volume of disease burden and high breast conservation rates. Despite a standard multimodality therapy the local, systemic, and CNS recurrence rates are high in TNBC and majority relapse within first 2 years after completion of therapy.

Deep Vein Thrombosis in Indian Cancer Patients Undergoing Major Thoracic and Abdomino-Pelvic Surgery.

The aim of the study was to determine the incidence of postoperative deep vein thrombosis (DVT) in Indian patients undergoing surgery for thoracic and abdomino-pelvic malignancies. A prospective observational study was conducted in a tertiary care cancer centre in North India. Two hundred and fifty consecutive patients who underwent curative surgery for thoracic and abdomino-pelvic malignancies during the period March 2014 to March 2015 were enrolled in the study. Perioperative pharmacological antithrombotic prophylaxis was not prescribed to any of the patient as per the institutional protocol. All the patients underwent colour duplex ultrasound of the bilateral lower limbs - preoperatively to determine the baseline status, and on 7th and 28th day postoperatively to look for presence of DVT. None of the patient in the study cohort showed clinical or radiological evidence of lower limb deep vein thrombosis. Our study suggests very low incidence of deep vein thrombosis in Indian patients undergoing surgery for thoracic and abdomino-pelvic malignancy.

End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we observed overexpression of End Binding Protein (EB1) in OSCC. In the present study we investigated the diagnostic and prognostic significance of alterations in expression of EB1 in oral cancer. METHODS: In this retrospective study, the expression of EB1 protein was evaluated in 259 OSCCs, 41 dysplasia, 166 hyperplasia and 126 normal tissues using immunohistochemistry and correlated with clinical-pathological parameters and prognosis of OSCC patients over a follow-up period of up to 91months. RESULTS: Significantly higher expression of cytoplasmic EB1 was observed in hyperplasia [p<0.001, OR=7.2, 95% CI=4.1-12.8], dysplasia (p<0.001, OR=21.8, CI=8.8-50.2) and OSCCs (p<0.001, OR=10.1, CI=5.8-17.4) in comparison with normal mucosa. Univariate analysis revealed cytoplasmic EB1 association with tumor grade, tumor size and recurrence of the disease. Kaplan Meier survival analysis of EB1 expression showed significantly reduced disease free survival (DFS) (p=0.003). Notably, OSCC patients showing cytoplasmic EB1 overexpression demonstrated significantly reduced DFS (p=0.004, HR=2.1). CONCLUSION: EB1 overexpression is an early event in oral tumorigenesis and cytoplasmic EB1 accumulation is associated with poor prognosis and tumor recurrence in OSCC patients.

Staging PET-CT Scanning Provides Superior Detection of Lymph Nodes and Distant Metastases than Traditional Imaging in Locally Advanced Breast Cancer.

BACKGROUND: This study was designed to evaluate the role of a single 18-FDG positron emission tomography and computed tomography (PET-CT) scan in comparison to multiple organ-directed conventional investigations (CI) as a staging tool in locally advanced breast cancer (LABC) to detect regional and distant metastasis. METHODS: All eligible patients were subjected to CI (chest X-ray, abdominal sonography, and bone scintigraphy) followed by a single 18-FDG PET-CT scan. Standard imaging criteria were used for diagnosis of metastasis. Histopathological confirmation was undertaken for suspicious lesions. An exploratory analysis was done to assess the impact of PET-CT on the staging of LABC and how it resulted in a change in management. RESULT: The study included 79 patients of LABC. PET-CT detected distant metastasis in 36 (45.5 %) patients while CI could identify distant metastasis in 20 (25.3 %) patients. Two of the 36 patients in whom PET-CT detected distant metastasis were false positive. Overall PET-CT upstaged the disease in 38 (48.1 %) patients as compared to CI: stage III to stage IV migration in 14 (17.7 %) patients due to identification of additional sites of distant metastasis, and within stage III upstaging in 24 (30.3 %) patients due to identification of additional regional lymphadenopathy. PET-CT led to a change in management plan in 14 (17.7 %) patients. CONCLUSION: PET-CT has a role in identifying additional sites of regional lymphadenopathy and distant metastasis to upstage the disease in a significant number of LABC patients in comparison to CI; this would help in accurate staging, selecting optimal treatment, and better prognostication of disease.

Recurrent sebaceous carcinoma of the eyelid: Outcome after postoperative reirradiation.

BACKGROUND: The purpose of this study was for us to describe a case of recurrent sebaceous carcinoma treated with postoperative reirradiation. METHODS: A 38-year-old man was diagnosed with sebaceous carcinoma of the right lower eyelid. The patient developed local recurrence 4 times, with the first one at 30 months after the excision. The first local recurrence was treated with excision and postoperative radiotherapy with 60 Gy/30 fractions/6 weeks. He manifested preauricular nodal metastasis with the third local recurrence, which was confirmed with (18)F-fluorodeoxyglucose positron emission tomography-CT ((18)F-FDG PET-CT). He received 2 courses of adjuvant reirradiation to the right orbit with 45 Gy/25 fractions/5 weeks and 30 Gy/15 fractions/3 weeks, respectively. RESULTS: The patient was successfully treated with no evidence of locoregional recurrence at 2 years after the cancer-directed therapy. The patient's follow-up from the date of diagnosis has been 9 years. CONCLUSION: Adjuvant reirradiation with modest doses may be considered with a view to provide disease control and long-term survival.

Nuclear heterogeneous nuclear ribonucleoprotein D is associated with poor prognosis and interactome analysis reveals its novel binding partners in oral cancer.

BACKGROUND: Post-transcriptional regulation by heterogeneous ribonucleoproteins (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal mucosa; its role in oral carcinogenesis remains unknown. Here in we determined the hnRNPD associated protein networks and its clinical significance in oral squamous cell carcinoma (OSCC). METHODS: Immunoprecipitation (IP) followed by tandem mass spectrometry was used to identify the binding partners of hnRNPD in oral cancer cell lines. Ingenuity pathway analysis (IPA) was carried out to unravel the protein interaction networks associated with hnRNPD and key interactions were confirmed by co-IP-western blotting. hnRNPD expression was analyzed in 183 OSCCs, 44 oral dysplasia and 106 normal tissues using immunohistochemistry (IHC) and correlated with clinico-pathological parameters and follow up data over a period of 91 months. Kaplan-Meier survival and Cox-multivariate-regression analyses were used to evaluate the prognostic significance of hnRNPD in OSCC. RESULTS: We identified 345 binding partners of hnRNPD in oral cancer cells. IPA unraveled novel protein-protein interaction networks associated with hnRNPD and suggested its involvement in multiple cellular processes: DNA repair, replication, chromatin remodeling, cellular proliferation, RNA splicing and stability, thereby directing the fate of oral cancer cells. Protein-protein interactions of hnRNPD with 14-3-3ζ, hnRNPK and S100A9 were confirmed using co-IP-western blotting. IHC analysis showed significant overexpression of nuclear hnRNPD in oral dysplasia [p = 0.001, Odds ratio (OR) = 5.1, 95% CI = 2.1-11.1) and OSCCs (p = 0.001, OR = 8.1, 95% CI = 4.5-14.4) in comparison with normal mucosa. OSCC patients showing nuclear hnRNPD overexpression had significantly reduced recurrence free survival [p = 0.026, Hazard ratio = 1.95, 95% CI = 1.0-3.5] by Kaplan-Meier survival and Cox-multivariate-regression analyses and has potential to define a high-risk subgroup among OSCC patients with nodal negative disease. CONCLUSIONS: Our findings suggest novel functions of hnRNPD in cellular proliferation and survival, besides RNA splicing and stability in oral cancer. Association of nuclear hnRNPD with poor prognosis in OSCC patients taken together with its associated protein networks in oral cancer warrant future studies designed to explore its potential as a plausible novel target for molecular therapeutics.

A phase 2 randomized study to compare short course palliative radiotherapy with short course concurrent palliative chemotherapy plus radiotherapy in advanced and unresectable head and neck cancer.

BACKGROUND: Treatment of unresectable HNSCC is not well defined and has a poor outcome. This study has been designed to address the unmet needs of such groups of patients with primary end points of (a) proportion of patients eligible for radical treatment in each arm (b) loco-regional disease control at 6months between two arms. MATERIALS AND METHODS: Locally advanced and unresectable HNSCC patients (except Nasopharynx and Larynx) unfit for radical treatment were randomized to arm A [short course RT alone (4Gy/#/day for 5days)] or arm B [RT as arm A+concurrent cisplatin at 6mg/m(2)/day IV bolus for 5days]. Those with at least PR were taken for further RT to complete biological equivalent dose of 70Gy, in both the arms. In arm B, concurrent CDDP at a dose of 40mg/m(2)/week was administered. RESULTS: 114 patients (57 in each arm) were randomized but 111 were analyzable. 15 (27.27%) patients in arm A and 28 (50%) patients in arm B had ⩾PR (p=0.01) however patients taken for FRT were 14 (25.45%) and 26 (46.42%) in arms A and B respectively (p=0.02). Locoregional control i.e. (CR+PR) at 6months was 16.36% in arm A versus 32.14% in arm B (p=0.15). Median PFS (arm A - 3.2months, arm B - 6.2months; p=0.02) and OS (arm A - 5.9months, arm B - 10.1months; p=0.03) was significantly more in arm B. There was relative improvement in quality of life for most parameters in arm B. CONCLUSION: Concurrent low dose CTRT can be an effective treatment modality in advanced and incurable HNSCC. However, a larger phase III trial is required.

Perioperative high-dose-rate interstitial brachytherapy combined with external beam radiation therapy for soft tissue sarcoma.

PURPOSE: The aim of our study was to evaluate the role of perioperative high-dose-rate interstitial brachytherapy (PHDRIBT) in combination with external beam radiation therapy (EBRT) in patients with localized soft tissue sarcoma (STS). METHODS AND MATERIALS: From year 2004 to 2010, 52 patients with localized STS were treated with wide local excision plus PHDRIBT followed by EBRT. Median size of the tumor was 8 cm (range, 4-19 cm). A single-plane interstitial brachytherapy implant with an average of nine catheters was performed during the surgical resection. The PHDRIBT was started on third postoperative day to deliver a high-dose-rate dose of 16 Gy in four fractions over 2 days using twice-a-day fractionation schedule. After 4 weeks, EBRT was started for a prescription dose of 50 Gy by conventional fractionation. Subsequently, chemotherapy was administered, if indicated as per our institutional policy. Patients were followed up regularly to study local control, survival, and toxicity. RESULTS: At a median followup of 46 months, no patient developed local recurrence, but 12 patients developed distant metastases. The 5-year overall survival and disease-free survival were 67% and 63%, respectively. Main acute toxicity was delayed wound healing observed in 3 patients (5.7%). Commonest late toxicity was chronic skin/subcutaneous fibrosis noticed in 5 patients (9.6%). CONCLUSIONS: The PHDRIBT combined with EBRT provides excellent local control and survival rates with acceptable acute and late toxicity in patients with localized STS.

Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients.

BACKGROUND: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and 5-year survival rates are about 50%. Identification of patients at high risk of recurrence will enable rigorous personalized post-treatment management. Most novel biomarkers have failed translation for clinical use because of their limited successful validation in external patient cohorts. The aim of this study was to determine the prognostic significance of alterations in sub-cellular expression of S100A2, a pro-tumorigenic calcium binding protein, identified as a candidate biomarker in our proteomic analysis in OSCC and validation of its clinical utility in an external cohort. METHODS: In a retrospective study, immunohistochemical analysis of S100A2 was carried out in 235 Indian OSCC (Test set) and 129 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 122 months for OSCC patients following the REMARK criteria. The findings were validated in an external cohort (Validation set 115 Canadian OSCC and 51 normal tissues) and data analyzed using the R package. RESULTS: Significant increase in cytoplasmic and decrease in nuclear S100A2 expression was observed in OSCC in comparison with normal tissues. Cox multivariable regression analysis internally and externally validated cytoplasmic S100A2 association with tumor recurrence. Kaplan Meier analysis of patients stratified to high and low risk groups showed significantly different recurrence free survival (Test set- log rank test, p = 0.005, median survival 16 and 69 months respectively and Validation set - p < 0.00001, median survival 9.4 and 59.9 months respectively); 86% and 81% of patients who had recurrence were correctly stratified into the high risk group. Seventy percent and 81% patients stratified into low risk group did not show cancer recurrence within 1 year in Test and Validation sets. CONCLUSIONS: Our study provided clinical evidence for the potential of cytoplasmic S100A2 overexpression as a predictor of recurrence risk in OSCC patients. A unique translational aspect of our study is validation of S100A2 as prognostic marker in two independent cohorts (Canadian and Indian) suggesting this protein is likely to find widespread utility in clinical practice for identifying oral cancer patients at high risk of disease recurrence.

Pulmonary metastasectomy: review of experience at a tertiary cancer care center.

BACKGROUND: Thirty to 40% of all extra thoracic cancers lead to secondary pulmonary lesions and approximately 20% of these cases feature metastases that are confined to the lungs. There is benefit of pulmonary metastasectomy in a select subset of patients. AIMS: The goal of this study was to evaluate the patient profile, treatment patterns, and outcomes following surgical treatment of lung metastasis and to identify prognostic factors for long-term survival. MATERIALS AND METHODS: Retrospective analysis of a prospectively maintained computerized database at a tertiary cancer care centre was done. 36 patients underwent curative resection for isolated pulmonary metastasis from January 1999 to December 2009. All metastasis were detected by non-contrast CT scan of the chest. Lung function tests were performed in all patients. Posterolateral thoracotomy was performed for resection of pulmonary metastasis by lung sparing procedures. A routine protocol of complete resection of all visible and palpable lung metastasis with a margin of 0.5 to 10 mm was followed in all patients. Staged thoracotomy was done for bilateral metastases. All palpable nodules were resected by wedge resection except in one case where pneumonectomy was done to achieve R0 resection. All patients underwent complete resection. CONCLUSIONS: Disease-free interval of more than 1 year along with less than 2 malignant nodules in patients with non-visceral pulmonary metastasis are variables identified in the present study which have enabled pulmonary metastasectomy to be offered as a safe therapeutic lifeline to patients.