282 CERVICAL ESOPHAGECTOMY USING “LARYNX ROTATION METHOD” CAN OBTAIN GOOD CLINICAL OUTCOMES.

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
Y Nakajima ◽  
K Ogiya ◽  
H Endo ◽  
T Okada ◽  
A Hoshino ◽  
...  
Keyword(s):  
Survival Rate ◽  
Clinical Outcomes ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Therapeutic Modality ◽  
Laryngeal Function ◽  
Larynx Preservation ◽  
Rotation Method ◽  
Significant Difference ◽  
Cervical Esophagectomy

Abstract   In the treatment of cervical esophageal carcinoma (CEC), preservation of laryngeal function is required as well as curability. Therefore, chemoradiotherapy (CRT) is often selected for larynx-preservation. In our department, larynx-preserving surgery using “larynx-rotation method” is aggressively carried out even when the oral side of the tumor margin extends beyond the esophageal orifice. In this study, we analyzed the clinical outcomes of the resectable CEC and examined ``Which therapeutic modality should be selected, surgery or CRT?'' Methods In the present study, 40 patients whose primary tumor was resectable Stage II/III CEC treated in our department since 2008, whose advanced primary tumor lesion was limited within cervical esophagus, and who undergo surgery or curative CRT were enrolled. The clinical outcomes were retrospectively analyzed. Results The Op group included 25 patients. All of the Op group patients could preserve the larynx. In the CRT group, 2 patients were performed pharyngo-laryngo-cervical esophagectomy as the salvage surgery. 1- and 3-year progression-free survival rate was 80.1 and 69.3% in the Op group, and 63.0 and 31.5% in the CRT group. 1-, 3- and 5-year overall survival rate was 95.8, 80.9 and 67.4% in the Op group and 78.6, 64.3 and 46.9% in the CRT group, respectively. Although there was no significant difference, the Op group showed relatively better clinical outcomes. Conclusion Cervical esophagectomy using “larynx-rotation method” could obtain good therapeutic outcomes while preserving the larynx. Especially in case cervical esophagectomy is sufficient as the curative resection, because the surgical invasion is little and the postoperative quality of life is good while preserving the larynx and the whole stomach, surgery is considered useful treatment modality.

scholarly journals A meta-analysis indicating extra-short implants (≤ 6 mm) as an alternative to longer implants (≥ 8 mm) with bone augmentation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoran Yu ◽  
Ruogu Xu ◽  
Zhengchuan Zhang ◽  
Yang Yang ◽  
Feilong Deng
Keyword(s):  
Survival Rate ◽  
Clinical Outcomes ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Bone Augmentation ◽  
Moderate Quality ◽  
Short Implants ◽  
Significant Difference ◽  
Complications Rate

AbstractExtra-short implants, of which clinical outcomes remain controversial, are becoming a potential option rather than long implants with bone augmentation in atrophic partially or totally edentulous jaws. The aim of this study was to compare the clinical outcomes and complications between extra-short implants (≤ 6 mm) and longer implants (≥ 8 mm), with and without bone augmentation procedures. Electronic (via PubMed, Web of Science, EMBASE, Cochrane Library) and manual searches were performed for articles published prior to November 2020. Only randomized controlled trials (RCTs) comparing extra-short implants and longer implants in the same study reporting survival rate with an observation period at least 1 year were selected. Data extraction and methodological quality (AMSTAR-2) was assessed by 2 authors independently. A quantitative meta-analysis was performed to compare the survival rate, marginal bone loss (MBL), biological and prosthesis complication rate. Risk of bias was assessed with the Cochrane risk of bias tool 2 and the quality of evidence was determined with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. 21 RCTs were included, among which two were prior registered and 14 adhered to the CONSORT statement. No significant difference was found in the survival rate between extra-short and longer implant at 1- and 3-years follow-up (RR: 1.002, CI 0.981 to 1.024, P = 0.856 at 1 year; RR: 0.996, CI 0.968 to 1.025, P  = 0.772 at 3 years, moderate quality), while longer implants had significantly higher survival rate than extra-short implants (RR: 0.970, CI 0.944 to 0.997, P < 0.05) at 5 years. Interestingly, no significant difference was observed when bone augmentations were performed at 5 years (RR: 0.977, CI 0.945 to 1.010, P = 0.171 for reconstructed bone; RR: 0.955, CI 0.912 to 0.999, P < 0.05 for native bone). Both the MBL (from implant placement) (WMD: − 0.22, CI − 0.277 to − 0.164, P < 0.01, low quality) and biological complications rate (RR: 0.321, CI 0.243 to 0.422, P < 0.01, moderate quality) preferred extra-short implants. However, there was no significant difference in terms of MBL (from prosthesis restoration) (WMD: 0.016, CI − 0.036 to 0.068, P = 0.555, moderate quality) or prosthesis complications rate (RR: 1.308, CI 0.893 to 1.915, P = 0.168, moderate quality). The placement of extra-short implants could be an acceptable alternative to longer implants in atrophic posterior arch. Further high-quality RCTs with a long follow-up period are required to corroborate the present outcomes.Registration number The review protocol was registered with PROSPERO (CRD42020155342).

Clinical outcomes of NSCLC patients with acquired RET rearrangement after resistance to osimertinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20626-e20626
Author(s):  
Chang Lu ◽  
Jia-Tao Cheng ◽  
Jin Kang ◽  
Yi-Hui Yao ◽  
Xiang-Meng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcomes ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Line Treatment ◽  
Significant Difference ◽  
Ret Rearrangement ◽  
Egfr Mutant

e20626 Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non- RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions: RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies. [Table: see text]

The impact of primary tumor site on outcomes of treatment with etoposide and cisplatin in grade 3 gastroenteropancreatic neuroendocrine carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 213-213
Author(s):  
Sang Eun Yoon ◽  
Jung Hoon Kim ◽  
Joon Young Hur ◽  
Su Jin Lee ◽  
Jeeyun Lee ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Neuroendocrine Carcinoma ◽  
Primary Tumor ◽  
Medical Center ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Significant Difference ◽  
The Impact

213 Background: Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a heterogeneous disease in terms of embryonic origin, aggressiveness, prognosis, and genomic profiling. Data regarding the efficacy of etoposide and cisplatin (EP) as a standard treatment of the primary tumor site in GEP-NEC are limited. Methods: We analyzed 64 patients with histopathologically confirmed metastatic GEP-NEC who received EP at Samsung Medical Center, Seoul, Korea, between January 2010 and January 2018. Based on primary tumor site, outcome of treatment with EP was evaluated. Results: Primary sites included 22 foregut-derived GEP-NECs (stomach, n = 6; duodenum, n = 4; pancreas, n = 12), 4 midgut-derived GEP-NECs, 5 hindgut-derived GEP-NECs of the rectum, 25 GEP-NECs originating from the hepatobiliary (HB) tract, and 12 GEP-NECs involving only intra-abdominal lymph nodes. No patient had a complete response (CR) and 17 had a partial response (PR), resulting in a 27.9% response rate (RR). When evaluating the efficacy of EP based on primary tumor site, the RR was most favorable in GEP-NECs involving only intra-abdominal lymph nodes, followed by GEP-NECs originating from foregut, midgut, HB, and hindgut. However, no statistically significant difference was observed for RR based on primary tumor site (p = 0.821). Similarly, no significant differences were found for progression-free survival (PFS) among patients with GEP-NECs arising from various primary tumor sites. Conclusions: Results from this study showed thatRR and PFS associated with EP treatment were not different based on the primary tumor site in patients with advanced or metastatic GEP-NEC.

scholarly journals Ten-Year Experience of Stereotactic Body Radiotherapy at a Single Institution: Impact of Technological Development on the Outcome of Patients With Early Lung Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382097916
Author(s):  
Keiichiro Koiwai ◽  
Yuuki Endo ◽  
Kai Mizuhata ◽  
Hironobu Ina ◽  
Ayumu Fukazawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Clinical Outcomes ◽  
Technological Development ◽  
Progression Free Survival ◽  
Strong Impact ◽  
Conventional System ◽  
Free Survival ◽  
Local Progression ◽  
Advanced System

Purpose: Advanced radiotherapeutic techniques and apparatus have been developed and widely applied in stereotactic body radiation therapy for early-stage non-small cell lung cancer, but their clinical benefits have not necessarily been confirmed. This study was performed to review our 10-year experience with therapy for the disease and to evaluate whether the advanced radiotherapeutic system implemented in our hospital 5 years after we began the therapy improved the clinical outcomes of patients. Materials and Methods: Patients who underwent the therapy at our hospital between April 2008 and March 2018 were retrospectively reviewed. They were divided into 2 groups treated with the conventional system or the advanced system, and the characteristics and clinical outcomes were compared between the groups. The same analyses were also performed in propensity-matched patients from the 2 groups. Results: Among the 73 patients eligible for this study, 42 were treated with the conventional system and 31 with the advanced system. All were treated as planned, and severe adverse events were rare. The local progression-free survival rate in the advanced system group was significantly higher than in the conventional system group (P = 0.025). In the propensity-matched patients, both the local progression-free survival rate and the overall survival rate were significantly higher compared in the advanced system group than the conventional system group (P = 0.089 and 0.080, respectively). Conclusion: The advanced system improved the outcomes of patients with the disease, suggesting that technological development has had a strong impact on clinical outcomes.

Association of telomere length (TL) with clinical outcomes in patients with colorectal carcinoma (CRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 418-418
Author(s):  
Mahadi Ali Baig ◽  
Amartej Merla ◽  
Titto A Augustine ◽  
Gil Atzmon ◽  
Temuri Budagov ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Copy Number ◽  
Tandem Repeats ◽  
Progression Free Survival ◽  
Housekeeping Gene ◽  
Tissue Samples ◽  
Paired Samples ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Metastatic Sites

418 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem.” During aberrant cell proliferations the normal check points of cell cycle is compromised leading to unrestricted cell division with extremely short T and subsequent genomic instability. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 122 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (>/< median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs. 5295 p=0.04). There was a trend towards increased overall survival (>/< median) with longer TL (4934 vs. 4117; p=0.08). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. Conclusions: TL is a potential biomarker predictive of clinical outcome (PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

Association of basophil to lymphocyte ratio (BLR) with clinical outcomes in metastatic hormone sensitive prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17049-e17049
Author(s):  
Katherine Emilie Rhoades Smith ◽  
Limeng Wan ◽  
Yuan Liu ◽  
Jacqueline T Brown ◽  
Greta Russler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Laboratory Data ◽  
Progression Free Survival ◽  
Continuous Variable ◽  
Cancer Center ◽  
Lymphocyte Ratio ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Hormone Sensitive

e17049 Background: There is limited biomarker data available for metastatic hormone sensitive prostate cancer (mHSPC). Inflammatory markers found on routine clinical lab data, including leukocyte to lymphocyte ratios calculated from complete blood counts (CBC), is associated with clinical outcomes (CO) in different malignancies. We investigated the association between basophil-to-lymphocyte ratio (BLR) and CO in a racially diverse patient population with mHSPC. Methods: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014 – 2020). Demographics, disease characteristics, and laboratory data were collected at the start of upfront therapy with either docetaxel (DOC) or abiraterone (ABI). Overall survival (OS) and progression-free survival (PFS) were used to measure CO. Results: Included were 165 patients with mHSPC with a median follow-up time of 22.6 months. 89 (53.9%) were Black and 76 (46.1%) were Non-Black (White, Asian, or Hispanic). 106 (63%) had Gleason scores of 8-10 and 105 (63.6%) were classified as high-volume disease (per CHAARTED trial criteria). 92 (55.8%) received DOC and 73 (44.2%) received ABI. Worse CO were associated with high BLR at an optimal cut of 0.0265 (range 0 – 0.81 , mean of 0.03, standard deviation 0.09). Elevated BLR is associated with decreased OS (HR 3.51, 1.79 – 6.91, p <0.001) and PFS (HR 1.85, 1.14 – 3.00, p 0.013) in multivariable analyses (MVA). High BLR and low BLR groups were similar except for age as a continuous variable, which was associated with high BLR. Otherwise, there were no significant difference for all reported clinical characteristics, including drug (DOC vs ABI), race (Black vs Non-Black), Gleason, disease volume (per CHARRTED criteria), ECOG, or BMI. Conclusions: In mHSPC, high baseline BLR is associated with worse OS and PFS. Our results are the first to identify that BLR is associated with CO in mHSPC. Further study is needed to validate BLR as a potential biomarker.[Table: see text]

Baseline neutrophil-to-eosinophil ratio (NER) and its association with clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (CPI).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16569-e16569
Author(s):  
Deepak Ravindranathan ◽  
Yuan Liu ◽  
Dylan J. Martini ◽  
Jacqueline T Brown ◽  
Bassel Nazha ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Clinical Benefit ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
P Value ◽  
Proportional Hazard ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Significant Difference

e16569 Background: Inflammatory markers have been studied as prognostic markers in patients with mRCC treated with CPIs. Recently, eosinophilia has been found to be associated with improved survival of patients with melanoma treated with CPIs. We reported baseline NER in patients with mRCC treated with CPIs and its association with clinical outcomes. Methods: We conducted a retrospective analysis of patients with mRCC treated with CPIs at Winship Cancer Institute from 2015-2018. Clinical outcomes were measured as overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from CPI-initiation to date of death and radiographic or clinical progression, respectively. Patients with baseline NER were categorized into high or low; high defined as NER > 49.2 and low defined as NER < 49.2. Univariate (UVA) and multivariate (MVA) analyses were carried out for OS and PFS using Cox proportional hazard model. Results: A total of 184 patients were studied with a median follow up of 25.4 months. Median age was 63 years old with 72% male and 20% black. About 25% were in high NER group. The high NER patients had significantly shorter OS in both UVA (HR: 0.58, p-value=0.017) and MVA (HR: 0.62, p-value=0.046) (Table). There was no significant difference between groups for PFS. Clinical benefit was seen in 47.3% of patients with low baseline NER and 40% with high NER. Conclusions: High baseline NER was associated with worse OS in patients with mRCC treated with CPIs. Larger, prospective studies are warranted to validate this hypothesis generating data.[Table: see text]

Interferon Alpha May Improve the prognosis of Advanced Myeloproliferative Neoplasm Patients with JAK2V617F Mutations

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5547-5547
Author(s):  
Liu Xiaoli ◽  
Li Ding ◽  
Na Xu ◽  
Bintao Huang ◽  
Xuan Zhou ◽  
...  
Keyword(s):  
Survival Rate ◽  
Adverse Reactions ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Essential Thrombocytosis ◽  
Free Survival ◽  
Overall Response ◽  
Significant Difference ◽  
Hydroxyurea Therapy

Abstract Objective Whetherinterferon alpha (IFN-α) has special therapeutic effect formyeloproliferative neoplasm (MPN) patients with JAK2V617F mutations was not widely confirmed. Our purpose was to evaluate the therapeutic effect of interferon alpha (IFN-α) in MPN patients with JAK2V617F mutations. Methods A total of 99 advanced MPN patients (including 68 polycythemia vera (PV) patients with 34 JAK2V617F mutations and 68 essential thrombocytosis (ET) with JAK2V617F mutations) patients) were enrolled to the study during 2007 to 2013 with informed consent, then they were divided into two groups: the IFN-α group (patients received a standard dose of IFN-α with (30-50)ug/d ) and the Hydroxyurea (HU) group (patients received a a dose of (0.25-0.5)g/d for HU). The progression-free survival rate were analyzed for a median of 32.0 (6.0 to 60.0) months follow-up period. Results The overall response rate between IFN-α and Hydroxyurea therapy groups of essential thrombocytosis (ET) patients with JAK2V617F mutations had no significant difference (88.2% vs 85.0%, P>0.05), but the 5-year progression-free survival rate of two groups showed significant difference (88.2% vs 55.0%, P<0.05). The overall response rate (78.6% vs 82.4% ) and 5-year progression-free survival rate (57.1% vs 58.8%) between IFN-α and Hydroxyurea therapy groups of ET patients without JAK2V617F mutations had no significant difference (P>0.05). The overall response rate between IFN-α and Hydroxyurea therapy groups of polycythemia vera (PV) patients with JAK2V617F mutations had no significant difference (80.0% vs 75%, P>0.05), but the 5-year progression-free survival rate of IFN-α and Hydroxyurea therapy groups showed significant difference (86.7% vs 50.0%, P<0.05). After the treatment of IFN-α and HU for six months, the ratio of Interferon-treated patients need to continue phlebotomy was significantly lower than hydroxyurea therapy group (8.3% vs 58.3%, P<0.05). The thromboembolic events,splenomegaly, bone marrow fibrosis of interferon treatment group were lower than hydroxyurea treatment group showed significant difference (P<0.05). The adverse reactions of IFN-α was moderate, most of the patients in this study could tolerate the therapy. The major side effect of hydroxyurea was hematologic adverse reactions (Grade 1-2) with mainly reduce of white blood cells and thrombocytopenia, which showed difference between IFN-α and hydroxyurea (P<0.05). Conclusions IFN-α may improve the prognosis of ET and PV patients with JAK2V617F mutations. Moreover, patients with PV and JAK2V617F mutations may be benefit for the treatment of IFN-α and could be recommended for an effective choice. Disclosures No relevant conflicts of interest to declare.

Marimastat as First-Line Therapy for Patients With Unresectable Pancreatic Cancer: A Randomized Trial

2001 ◽  
Vol 19 (15) ◽  
pp. 3447-3455 ◽  
Author(s):  
S. R. Bramhall ◽  
A. Rosemurgy ◽  
P. D. Brown ◽  
C. Bowry ◽  
J. A.C. Buckels ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Randomized Study ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Survival Times ◽  
Significant Difference

PURPOSE: The prognosis for unresectable pancreatic cancer remains dismal (1-year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer performed to date, compares marimastat, the first of a new class of agents, with gemcitabine. PATIENTS AND METHODS: Four hundred fourteen patients with unresectable pancreatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m2. The primary end point was survival. Progression-free survival, patient benefit, and safety were also assessed. RESULTS: There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P = .19). Median survival times were 111, 105, 125, and 167 days, respectively, and 1-year survival rates were 14%, 14%, 20%, and 19%, respectively. There was a significant difference in survival rates between patients treated with gemcitabine and marimastat 5 and 10 mg (P < .003). Both agents were well tolerated, although grade 3 or 4 toxicities were reported in 22% and 12% of the gemcitabine- and marimastat-treated patients, respectively. The major toxicity of marimastat was musculoskeletal (44% of marimastat patients, compared with 12% of gemcitabine patients; musculoskeletal toxicity was severe in only 8% of marimastat patients). CONCLUSION: The results of this study provide evidence of a dose response for marimastat in patients with advanced pancreatic cancer. The 1-year survival rate for patients receiving marimastat 25 mg was similar to that of patients receiving gemcitabine. In view of the manageable tolerability of marimastat and its ease of administration, further studies are warranted.

Association of telomere length with clinical outcomes in patients with colorectal carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14540-e14540
Author(s):  
Mahadi Ali Baig ◽  
Titto A Augustine ◽  
Amartej Merla ◽  
Gil Atzmon ◽  
Temuri Budagov ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Copy Number ◽  
Tandem Repeats ◽  
Progression Free Survival ◽  
Housekeeping Gene ◽  
Tissue Samples ◽  
Paired Samples ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Metastatic Sites

e14540 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem”. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 118 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (>/< median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Stage at diagnosis (localized Vs Metastatic) had a statistically significant difference in TL (mean BP 4047 vs. 5704; p=0.03). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs 5295 p=0.022). Patients treated with cetuximab/panitumumab who had Shorter TL were also found to have significantly decreased Overall Survival (OS) (101.1 Months vs 153.02 Months p<0.0001). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. There was no difference of TL seen with size of the tumor. Furthermore there was no difference in TL between various metastatic sites. Conclusions: TL is a potential biomarker predictive of clinical outcome (OS & PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

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