Recurrence pattern with respect to two different dose fractionations in patients with locally advanced head and neck cancer treated with chemoradiation using image-guided volumetric arc therapy.

BACKGROUND: Patients with head and neck cancer were treated with either 70 Gy in 35 fractions (Arm A) or 66 Gy in 30 fractions (Arm B). MATERIALS AND METHODS: Total 168 patients of carcinoma oropharynx, larynx, and hypopharynx treated with radical chemoradiation in two Arm A versus B (65 vs. 103 patients). RESULTS: With a median follow-up of 16 months (0-67), 2 year disease-free survival (DFS) and overall survival (OS) was 56.3% versus 62.1% (p = 0.64) and 44.5% versus 53.0% (p = 0.51) in Arm A versus B. Total 22 (33.8%) versus 28 (27.2%) failed locoregionally. Majority of failures were infield for both primary (17 vs. 23 cases) and nodes (13 vs. 12) in Arm A versus B. Ten (71.4%) vs. 10 (76.9%) had nodal failure in index nodal level only. CONCLUSION: Commonly seen failure in head-neck radical chemoradiation is within infield high-risk volume, nodal failure being most common in index nodal level.

Docetaxel/Oxaliplatin/Capecitabine (TEX) triplet followed by continuation monotherapy in advanced gastric cancer.

INTRODUCTION: Docetaxel/oxaliplatin/capecitabine (TEX) is a commonly used combination chemotherapeutic regimen in advanced gastric cancer (AGC). Application strategies in routine clinical practice are reported in this study. MATERIALS AND METHODS: Patients diagnosed with AGC, receiving biweekly TEX (docetaxel - 60 mg/m (2)-D1; oxaliplatin - 85 mg/m (2)-D1, and capecitabine 500-625 mg/m (2) orally twice daily for 14 days) between July 2012 and May 2016 were retrospectively analyzed for tolerance, prognostic factors, event-free survival (EFS), and overall survival (OS). The proportion of patients continuing and terminating chemotherapy at various time-points was enumerated. RESULTS: Overall, 208 patients were started on TEX. Median EFS was 6.34 months (95% confidence interval [CI] 5.80-6.87), and median OS was 15.31 (95% CI 12.65-17.96). Post 8 cycles of TEX, further 30 patients (14.4%) were continued on chemotherapy (docetaxel, capecitabine, or TEX) whereas 47 patients (22.6%) were on observation only, and there was a statistically significant difference in the median OS of these two groups (22.55 months vs. 14.89 months; P = 0.028). Raised serum alkaline phosphatase (SAP) levels (>100 U/L) predicted inferior survival (P = 0.006). CONCLUSION: TEX chemotherapy is a feasible, efficacious triplet regimen that can be used in clinical practice. SAP levels >100 U/L is a poor prognostic factor, as observed in this study. An initial "induction" such as combination chemotherapy regimen followed by monotherapy as continuation requires further evaluation.

Clinical practice and outcomes in advanced gastrointestinal stromal tumor: Experience from an Indian tertiary care center.

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.

Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib.

BACKGROUND: The exon 11 KIT mutant gastrointestinal stromal tumors (GIST) is a heterogeneous cohort with variable biological behavior based on different mutational subtypes. METHODS: Patients with histologically proven GIST with KIT exon 11 mutations were selected from a prospectively maintained database, and evaluated for clinical characteristics and event free survival (EFS). Patients were divided into mutations upstream to codon 557 (G1), mutations involving codon 557-558 (G2) and mutation downstream to codon 558 (G3). RESULTS: A total of 90 patients satisfied the inclusion criteria for study. Substitutions, indels and duplications were seen in 23 patients. Deletions were seen in 67 patients, of which 44 patients had large deletions (>6 base pairs), while 23 has small deletions (<6 base pairs). Complex mutations were seen in 15 patients. G2 mutations were noted in 33 patients, while G1 and G3 mutations were seen 32 and 25 patients respectively. With a median follow-up of 26 months, estimated median EFS for the entire cohort was 55 months. The G2 cohort had an inferior EFS compared to the G1 and G3 cohorts (46 vs. 55 months), but this did not achieve statistical significance (univariate analysis: P=0.075). On multivariate analysis, patients undergoing radical intent surgery vs. no surgery (58 vs. 55 months; P=0.005) and G1 or G3 vs. G2 cohort (P=0.058) showed trend towards improved EFS. CONCLUSIONS: In patients with GIST exon 11 codon 557-558 mutation subset there is a trend towards an inferior survival even when treated with imatinib mesylate (IM).

Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis.

PURPOSE: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. MATERIALS AND METHODS: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. RESULTS: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. CONCLUSIONS: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resection, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

Nontrial, real-world outcomes in unresectable locally advanced pancreatic cancer: Chemotherapy and chemoradiation is the standard while surgery is uncommon.

BACKGROUND: Outcomes and survival of truly unresectable locally advanced pancreatic cancers (LAPC) is often reported along with borderline resectable pancreatic cancers especially from a real world cohort. METHODS: The audit of LAPC patients, diagnosed based on the NCCN criteria between February 2013 and January 2016 was used to identify patients starting and continuing treatment in our institution. Practice patterns, outcomes and prognostic factors for overall survival were evaluated. RESULTS: Of the 83 patients, 52 were available for inclusion in the analysis. Median age was 56 years (range 30- 77), with males constituting 75% of patients. Baseline comorbidities seen were diabetes mellitus, hypertension and cardiac dysfunction in 46.1%, 69.1% and 52% of patients respectively. 84.6% of patients had arterial vascular involvement as criteria for unresectable LAPC. 50% of patients received chemotherapy only, while the remainder received chemotherapy and concurrent chemoradiation. One patient was able to undergo curative R0 resection. FOLFIRINOX was the most commonly used chemotherapy regimen (53.8%). With a median follow up of 15.9 months, median progression free survival (mPFS) was 7.26 months (95% CI: 5.75-8.76) and median OS was 11.8 months (95% CI: 9.96 - 13.61). None of the potential prognostic factors evaluated, i.e., age, gender, nodal status, pre-treatment CA 19.9 levels, showed correlation with OS. CONCLUSION: This analysis shows outcomes in unresectable LAPC comparable to existing literature. Surgery in unresectable LAPC patients is less common than seen in previously published studies, more likely due to this cohort being truly 'unresectable' in terms of major arterial involvement.

Personalized treatment approach to gastroenteropancreatic neuroendocrine tumors: a medical oncologist's perspective.

The medical management of gastroenteropancreatic neuroendocrine tumors involves treatment of symptomatic disease related to hormone secretions or bulky unresectable metastatic disease. Combining gallium DOTA with fluorine-18 fluorodeoxyglucose-PET along with histopathological grading helps to determine tumor heterogeneity and seek reasons for poor response to therapy. In the light of adding chemotherapy in selected patients with intermediate-grade tumors, the newer scan helps in personalization of the therapy along with the biopsy. The tumor dedifferentiation over the particular time period leading to aggressive behavior, a well-known entity, is contrasted with the redifferentiation phenomenon in some patients as a result of chemotherapy or targeted drug therapy. This may support the basis for combining peptide receptor-targeted radiotherapy/octreotide therapy with chemotherapy or mTOR inhibitors such as everolimus.