A significant number of patients with colorectal cancer (CRC) benefit from adjuvant therapy. While 6 months of FOLFOX is standard of care, newer regimens like CAPOX and SOX allow for shorter durations. Trials of importance include SCOT (U.K., Denmark, Spain, Sweden, Australia, New Zealand), TOSCA (Italy), Alliance/SWOG80702 (U.S., Canada), IDEA (France), ACHIEVE (Japan), and HORG (Greece). Management recommendation is also based on patient preferences, dividing them into fighters and fatalists. Better patient selection is possible with the use of novel molecular-based biomarkers and circulating tumor deoxyribonucleic acid monitoring of minimal residual disease. There also needs to be special consideration for the geriatric patients—especially due to their limited mobility, comorbidities, and polypharmacy.
e15101 Background: There is no standard second-line chemotherapy after progression on 1st line therapy Gemcitabine and platinum combination chemotherapy, in locally advanced (unresectable) and metastatic Gall bladder cancer (LA/MGBC) patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. Methods: In this prospective study, patients of LA/MGBC, with performance status ≤2, who progressed on first line therapy, were randomly enrolled from May 2012 to June 2013. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. The response rates(RR), time to tumour progression(TTP) and overall survival (OS) were analyzed. Toxicity profile was recorded as per common toxicity criteria version 4. Results: Total 50 patients were enrolled. The median age of patients was 52 yrs (32yrs – 66yrs), out of which 16 (32%) were males and 34 (68%) were females. The median no. of cycles could be given were 11 (2-12). Only 50% patients in this study completed full twelve cycles of chemotherapy. 12 patients (24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 31(62%) patients, with CR in none, PR in 12 (24%), SD in 19 (38%) and PD in 19 (38%) patients. The median TTP was 3.8 months, median OS was 6 months. The main grade 3/4 side effects seen were hematological in 28% (n=14) and gastrointestinal in 26% (n=13) patients. Majority of patients (44%) had grade 1/2 peripheral neuropathy. Conclusions: FOLFOX-4 is an effective and well tolerated regimen as a second line treatment in LA/MGBC patients.
3062 Background: Post curative-intent surgery and therapy, the presence of circulating tumor DNA (ctDNA) load represents Minimal Residual Disease (MRD). Conversely, presence of Circulating Tumor Cells (CTCs) in I-II cancer stage or even in disease free survival (DFS) patients indicates occult Cellular Residual Disease (CRD) with undetectable micro-metastasis. Thus these complementary biomarkers undergoing treatment are the indicators of non-responsiveness outcome suggesting the treatment modifications. Methods: Retrospectively, we monitored a cohort of 46 cancer patients for MRD using ctDNA and CTCs- treated or undergoing treatment (e.g. lung, breast, colon, HNC (n = 14, 7, 6, 4, respectively). OncoMonitor test detected single nucleotide variation (SNVs), small insertions and deletions (INDELs), copy number variations (CNVs), and translocations (fusions). Libraries were prepared using a hybridization-capture method covering 1000 targets with mean sequencing depth 5000X on Illumina Nextseq 2000 in a pair-end mode (150 x2). Variant calling was performed using a proprietary bioinformatics pipeline iCare. CTCs were isolated using the OncoDiscover platform possessing anti EpCAM antibody based immunomagnetic system per 1.5 mL blood. CTCs were confirmed with CK18+, PD-L1 and CD45 using a motorized fluorescence microscope. Results: From ctDNA, 47.82% (n = 22) of patients identified with at least 1 actionable genomic finding. 13.04% (n = 6) patients showed EGFR driver mutations. Also, 19.56% (n = 9) patients were identified with either EGFR driver/KRAS/PI3K passenger mutations with 4.34% (n = 2) identified with ALK-EML4 fusion. The average ctDNA load obtained in patients with progressive disease (n = 26) was 8.2 molecules per 1mL of plasma. At least 1 CTC was detected in 61.53% (n = 16) of progressive disease patients with the highest of 4 CTCs identified in 7.69% (n = 2) of patients. Only 30% (n = 6) of patients with stable disease were identified with at least 1 genomic finding from a total of 20 patients upon ctDNA analysis with an average ctDNA load of 2.2 molecules per 1mL of plasma. Patients with clinically progressive disease showed ctDNA load ~4 fold higher than in patients with stable disease upon treatment. No patients were identified with 4 CTC in the stable disease cohort as opposed to 7.69% in progressive disease patients upon treatment. Conclusions: We observed ctDNA and CTCs complementing MRD status, even post curative-intent surgery and therapy with prophecy for such patients likely to progress. Our findings are strongly indicative of positive correlation between ctDNA load, number of CTC detected, and disease progression from radiological findings for practical and clinical decisions. More studies in this direction are imperative to attain the follow ups for better clinical outcome.
ABSTRACT A 30-years-old female with diagnosis of carcinoid tumor of right bronchus was planned to undergo right pneumonectomy under combined epidural and general anesthesia. A pediatric transesophageal echocardiography (TEE) probe was inserted for intraoperative monitoring of the right ventricular function. It also showed spinal canal structures (dura matter, epidural and subarachnoid space and spinal cord) and helped in visualization of local anesthetic spread in the epidural space. How to cite this article Kumar B, Goswami V, Rana SS, Puri GD. Utility of Transesophageal Echocardiography in Confirmation of Spread of Local Anesthetic in the Epidural Space. J Perioper Echocardiogr 2013;1(2):72-74.
The preservation of irrigation water is often of primary importance to the agriculture development of a country. The reduction or eliminate of seepage losses in irrigation canals by means of linings assures better utilization of the conveyed water and an improved economic situation, seepage losses from earthen irrigation channels depend on a number of factors and vary from (30 to 50) percent of the discharge available at the head of an irrigation system. The main focus of the study was to determine the seepage losses through lined canal. The studies on estimation and measurement of seepage losses were of much interest to the irrigation scientist. The research workers have done lot of work on the seepage aspect of the irrigation water management. The main objective of this investigation study is to measure seepage losses between Masitawali (Hanumangarh) head to Bridhwal head (Shri Ganga Nagar), to determine the rate of conveyance losses at a limited section of Indira Gandhi Nahar Project, the comparison of measurement of water losses with inflow-outflow and ponding method, to check out the conveyance efficiency of earthen watercourse and to determine the total quantity of water lost from earthen water course with seepage alone.
Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors are a unique class of therapeutic agents that focus on tumors with deficiencies in the homologous recombination DNA repair mechanism. Genomic instability outlines high-grade serous ovarian cancer, with 50% of all tumors displaying defects in the important DNA repair mechanism of homologous recombination. Earlier research studies have demonstrated considerable efficiency for PARP inhibitors in patients with germ line breast-related cancer antigens 1 and 2 (BRCA-1/BRCA-2) mutations. It has also been observed that BRCA wild-type patients with other defects in the homologous recombination repair mechanism get benefited from this therapy. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The selection of PARP inhibitor is mainly dependent upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of cases which are most likely to get benefited from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The purpose of this review is to focus and describe the current evidences for PARP inhibitors in ovarian malignancy, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolving resistance.
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