tbuckley/cabot-search huggingface dataset:
Retreatment after the failure of initial epidermal growth factor receptor inhibitor in non-small cell lung cancer.
Authors: T. An, J. Wang, H. Bai, M. Wu, J. Zhao, J. Duan, Y. Wang, Z. Wang, L. Yang
Journal: Journal of Clinical Oncology (2011)

e18048 Background: The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) including gefitinib and erlotinib shows favorable antitumor activity against cheomrefractory non small cell lung cancer (NSCLC). More recently, EGFR-TKI also shows antitumor activity in first-line therapy. However, patients with advanced NSCLC have few treatment options available if they are refractory to EGFR-TKI. Methods: This study retrospectively analyzed 71 patients who experienced treatment failure from their initail use of EGFR-TKI. After more than 1 month from the time of discontinuation of the initial TKI treatmenT, they were retreated with TKI as further tumor progression was observed. Results: Of the 71 patients, 26 (36.6%) patients were well controlled by retreatment with TKI monotherapy for more than 3 months. 5 (7.1%) patients had partial response. Exon 21 mutation, PFS more than 6 months during initial treatment TKI, and the interval more than 3months between initial treatment and retreatment with TKI was associated with a good progression free survival based on univariate Cox analysis (P=0.034; P=0.013; P=0.046). Conclusions: This study suggest the possibility that retreatment with TKI might be useful when 1) initial treatment shows a favorable PFS(more than 6 months), and 2) there has been a period of time (more than 3 months) following the termination of the initial TKI treatment, and 3) Exon 21 has active mutation.
High relapse rates and poor survival of native Hawaiian (NH) women with HER2-positive breast cancer.
Authors: C. D. K. Chong, L. Loo, L. Wilkens, C. Caberto
Journal: Journal of Clinical Oncology (2011)

e11116 Background: The Hawaii Tumor Registry reports of higher mortality rates and advanced disease at diagnosis for Native Hawaiian (NH) women with breast cancer may represent a biologically more aggressive cancer complimented by HER2 overexpression. This study investigates the association of HER2 overexpression potentiating NH breast cancer leading to early relapses and poor survival. Methods: This retrospective study analyzed data for women diagnosed with breast cancer from 2000-2005, and followed through 2007 (n=1488), at the Queen’s Medical Center in Honolulu, Hawaii. This study focused on three major ethnicities: NH (n=359), Japanese (JA; n=609) and Caucasian (CA; n=520) women. Demographics on tumor grade, stage, ER, PR, and HER2 expression were obtained from the hospital’s cancer registry. Cox regression models of 1) relapse; 2) death for these patients were used to evaluate the association of intrinsic breast cancer subtypes and ethnicities. Survival time was the interval between diagnosis and death or cessation of follow-up at 2007. Results: We compared the frequency distribution of tumor subtypes (Luminal A, Luminal B, HER2-positive, and Triple Negative). Triple Negative breast cancers were associated with increased risk of death for the NH women (Hazard Ratio (HR)=2.8, p=0.046) and JA (HR=2.2, p=0.052). HER2-positive breast cancers were associated with increased risk of death for NH (HR=2.6, p=0.044) and CA (HR=2.9, p= 0.018) women, but not for the JA women. In HER2+ tumors, we observed that there was a significant increase in the frequency of relapse for NH (23.6%) compared to JA (9.8%) or CA (10%) women. Cox regression analysis indicate that NH women are more likely to relapse (HR=3.28) compared to JA (HR=1.05) or CA (HR=1.2) women. Conclusions: These data illustrate the importance of cross-ethnic studies in understanding racial/ethnic based differences in breast cancer incidence and mortality. We observed that Her2 overexpression is associated with disproportionately higher relapse and mortality rates in NH women with breast cancer. An ethnicity - HER2 interaction is suggested by this data and further molecular studies are indicated.
Time to first-line chemotherapy and travel distance to the cancer center and their relationship to subsequent-line therapies in stage IV CRC.
Authors: Mahjabeen Fatima Iqbal, Aleksi Emil Suo, Neha Papneja, Nayyer Iqbal, Tahir Abbas, Kamal Haider, Adnan Zaidi, Shahid Ahmed
Journal: Journal of Clinical Oncology (2016)

724 Background: Second and third line therapies in stage IV colorectal (CRC) have been associated with significant improvement in survival. However, not all patients receive all available therapies. Delay in starting treatment and travel burden can affect patient access and use of future therapy. Little is known about time to first line chemotherapy (TC) and travel distance to cancer center (TD) and their relationship to future therapies in stage IV CRC. The study aims to determine relationship between TC and TD with second and subsequent line of therapies. Methods: A patients cohort diagnosed with synchronous stage IV CRC during 2006-2010 in the province of Saskatchewan, Canada was studied. Patients with ECOG performance status of &gt; 1 or who did not receive chemotherapy were excluded. The logistic regression analyses were performed to assess relationship between TC and TD and subsequent line therapies. Results: 569 patients were diagnosed with synchronous stage IV CRC. 326 patients received first line chemotherapy (mostly FOLFIRI ± bevacizumab). Of 326 patients 62 with ECOG performance status (PS) &gt; 1 were excluded. The median age of 264 eligible patients was 62 yrs (IQR:53-72). 61% were male and 38% had ECOG PS of 0. Mean Charlson score was 9±1.3. 24% underwent metastasectomy. Median TC was 77 days (IQR: 53-107) and median TD was 64.4 km (IQR:4.8-166). 42.8% patients had to travel &gt; 100 km for their treatment. Of 326 patients 144 (55%) received future therapies. On multivariate analysis absence of comorbid illness (as per Charlson comorbid index), odd ratio (OR) 1.45 (95% CI: 1.19-1.77), no metastasectomy, OR 1.89 (1.03-3.46) and TD &lt; 100 km, OR 1.69 (1.003-2.84) were correlated with the utility of 2 nd and subsequent line therapies. Conclusions: Our result revealed that although time to first line chemotherapy did not correlate with future systemic therapies, travel distance to Cancer Center &gt; 100 km was associated with low rate of second or subsequent line therapies in statge IV CRC patients with good performance status.
Use of perioperative therapy in gastric cancer: A retrospective comparison of ECF and chemoradiation.
Authors: V. Siripurapu, J. C. Watson, J. P. Hoffman
Journal: Journal of Clinical Oncology (2011)

112 Background: Gastric Cancer (GC) remains a major cause of cancer related morbidity and mortality in Western Countries with five year survival rates between 30%-40%. Preoperative therapy has been championed by groups extrapolating data from the Intergroup 0116 and the MAGIC trials, with a view to enhancing completion of therapy and improving survival in locally advanced tumors. Methods: Patients with preoperative treatment of GC were reviewed from our tumor registry. Stages were assigned by AJCC 7 th edition. A comparison between the ECF regimen and non-ECF chemoradiation regimens was performed to view patterns of pathologic complete response (pCR), recurrence, toxicity and overall survival. Results: Forty-two patients were identified and stratified into two groups; Group 1 ECF treatment arm (n = 16) compared to group 2 non-ECF chemo-radiation arm (n = 26). No statistical difference was noted in age, ethnicity or stage stratification. All of Group 1 received their chemotherapy regimen after 2005. In contrast, 60% of Group 2 patients received their treatment pre-2005. Only 56% the ECF group completed their treatment course (19% received other postoperative therapy). Seventy percent of group 2 received adjuvant chemotherapy. A grade 2 or higher toxicity was noted in 16% of Group 1 compared to 60% in Group 2 (p = 0.035). Seven complications were noted in the group 1 compared to 10 in group 2 (p = NS). The differentiation of tumor between groups was not significant (p = 0.97). Length of stay was significant (Group 1:9 days, Group 2:12 days, p = 0.02). More nodes were retrieved from group 1 versus group 2 (20.2 versus 15.2, p = 0.03). Group 1 had 3 recurrences (19%) while Group 2 had 11 recurrences (42%, p = 0.94). In both groups 80% of recurrences were distant. Group 1 had a 19% pCR versus 23% in group 2 (p = 0.79). Two-year survival was 70% in both groups, with a median survival of 51 months for group 2. Median survival was not reached for group 1. Conclusions: No difference was noted in pCR, recurrences, or survival between these two regimens. If this can be confirmed in larger, prospective, randomized trials, use of radiation and its potential morbidity may be avoided. No significant financial relationships to disclose.
Using an online portal and nurse navigators to improve access to cancer care between network hospitals.
Authors: Eleanor Miller, Margaret Rummel
Journal: Journal of Clinical Oncology (2014)

126 Background: Nurse navigation-facilitated access to cancer care is an emerging trend in healthcare. One way to improve access to specialized cancer care is through nurse navigators in collaboration with affiliated network hospitals. The Abramson Cancer Center (ACC) has a network of 15 community hospitals in the tri-state area that provides patients access to an academic medical center for subspecialty care that is not always available the community cancer center. Methods: In 2010, a navigation referral process was developed using nurse navigators from the ACC and the network hospitals. Then in 2012, an online portal was developed to further streamline physician referrals to and from the ACC. Updates were made to the online portal in 2013 and 2014 for continued improvement. Results: Prior to the online portal, no central repository for network referrals existed to ensure that patients were scheduled with the correct provider(s). Now with the portal patients are referred, assessed, and scheduled with appropriate providers by the nurse navigator. This has increased accountability and streamlined the scheduling process. Now, patients can be seen by multiple providers during one visit to the ACC. It has also provided a network for the ACC nurse navigators to connect patients back to the community setting for ongoing care once consults or treatments at the ACC are completed. Since the navigation process was implemented, over 1200 patients have been referred (over 500 in the past year alone) for second opinions, clinical trials, proton radiation, bone marrow transplants, surgical options, and cutting- edge technology that may not have otherwise been available. Conclusions: Using nurse navigators at the core of the process ensures that patients are triaged and scheduled in a timely and medically-appropriate manner, thus enhancing their access to specialized cancer care.
Assessment of bowel disorders following radial cystectomy and urinary diversion for muscle-invasive transitional cell carcinoma of the bladder.
Authors: Mario W. Kramer, Mohammad Kabbani, Abdul-Rahman Kabbani, Christoph A. J. von Klot, Hossein Tezval, Inga Peters, Thomas R. W. Herrmann, Markus A. Kuczyk, Axel S. Merseburger
Journal: Journal of Clinical Oncology (2014)

347 Background: Articles reporting and specifying bowel disorders after radical cystectomy as long-term complications are sparse. However, numerous patients report on bowel function alteration and/or defecation disorders or even stool incontinence. For better qualification and quantification we present our data of a large cohort of patients evaluated with a newly developed questionnaire. Methods: For this purpose a novel non validated questionnaire was developed. The questionnaire was sent to 253 patients who had been treated with radical cystectomy between 2006 and 2012 to assess possible changes in bowel function and its impact on health related quality of life. Of those, 89 patients reported on their current status. Questions were related to their overall satisfaction as well as to their quality and severity of bowel disorders following pelvic surgery for bladder cancer. Results: In total 40 (44.9%) patients reported of a persistent change in bowel function after surgery. Most frequent were constipation (28.9%), diarrhea (18.4%) or both (21.1%) followed by flatulence (31.6%). Patients who experienced bowel function alteration but who are still satisfied reported predominantly of constipation (35.3%) and flatulence (41.2%) but not diarrhea. Twenty-three (25.8%) patients are currently not satisfied with their bowel function. Of those, 82.6% complaint about frequent flatulence, 75% report on softer stools, 65.2% have irritable bowel symptoms, 26.1% experience faecal incontinence and 73.9% are affected by serious life restrictions due to bowel disorder. Defecation frequency increased significantly (p&lt;0.001). There is a significant reduction in life quality (p=0.004), medical condition (p=0.008) and energy level (p=0.035). A significant correlation could be found for higher T-stage (p&lt;0.05) and positive lymph nodes (p&lt;0.03). No differences could be observed between patients who received ileal-conduit vs. orthotopic neobladder or MAINZ I pouch urinary diversion. Conclusions: Long-term bowel disorders after cystectomy are an underestimated issue. A better understanding might lead to modifications of surgical procedures.
The effects of <i>H. pylori</i> CagA on DNA amplification and protein expression status of the HER2 gene in gastric cancer.
Authors: Jung Ho Shim
Journal: Journal of Clinical Oncology (2014)

67 Background: We investigated whether Cag A contributes to the DNA copy change and expression of the HER2 gene mRNA transcript and, consequently, affects HER2 protein expression to evaluate the significance of H. pylori Cag A and HER2 amplification in gastric cancer. Methods: We used the AGS gastric cancer and HFE-145 immortalized non-neoplastic gastric mucosa cell lines to investigate whether Cag A regulates DNA copy number and HER2 expression. We also confirmed the effects of Cag A on gastric cancer tissues. Immunohistochemistry with or without fluorescence in situ hybridization (FISH) was conducted to determine the level of HER2 protein expression based on the revised criteria in the HER2 test guidelines. Results: H. pylori CagA transfected AGS cells showed a significant increase in HER2 gene copy number and expression. In addition, Cag A expression was detected in 17 (56.7%) of 30 gastric cancer (GC) tissues, and eight (47%) showed HER2 DNA amplification of more than two-fold (P = 0.013). A positive correlation was observed among DNA copy number, the mRNA transcript, and HER2 gene protein expression (p &lt; 0.05). HER2 overexpression was detected in 12 (40%) of 30 gastric cancers by Hoffman’s criteria. Conclusions: These results suggest that H. pylori CagA may induce overexpression of the HER2 gene protein by increasing HER2 DNA and mRNA copy number. To overcome the weakness of the current HER2 assessment criteria, we propose to test HER2 DNA copy number changes with immunohistochemistry, instead of FISH.
A randomized phase II trial of pre-operative docetaxel and cisplatin (DP) or docetaxel alone (D) in clinical (c-) stage IB/II non-small cell lung cancer (NSCLC): Initial report of Japan Clinical Oncology Group trial (JCOG 0204)
Authors: H. Kunitoh, H. Kato, M. Tsuboi, H. Asamura, H. Tada, K. Nagai, T. Mitsudomi, T. Koike, N. Ishizuka, N. Saijo
Journal: Journal of Clinical Oncology (2005)

7119 Background: There are few data on optimal pre-operative chemotherapy (Cx) in early c-stage NSCLC. We conducted a randomized phase II trial in order to evaluate the safety and efficacy of the preoperative platinum-based doublet Cx and D monotherapy in c-stage IB/II, resectable NSCLC. Methods: Patients (pts) with pathologically documented c-stage IB/II NSCLC, performance status (PS) 0–1 and ample organ functions were eligible. Mediastinal nodes >=1cm on CT scan must be biopsied and proved to be negative via mediastinoscope. Pts were randomized to receive either two cycles of DP given q4 (q3 allowed) weeks: P 80mg/m2 and D 60mg/m2 on day 1, or, three cycles of D 70mg/m2 q3weeks. Pts went on to thoracotomy 4–5 weeks (DP) or 3–4 weeks (D) after completion of the Cx. Preoperative Cx could be stopped and switched to surgery when tumor size increased >=10% in diameter. Primary endpoint was 1-year disease-free survival (DFS) rate. Results: From Oct./02 to Nov./03, 80 pts were randomized. Median age 65 (range 30–74), M/F 62/18, c-IB/II 45/35, PS 0/1 66/14, histology Ad/Sq/Others 54/21/5 (including 1 ineligible sarcoma). As of Dec./04 monitoring, all 79 eligible pts (40 in DP and 39 in D) were reported to be treatment-off and followed up for 1 year. Cx toxicities were mainly hematologic and well tolerated. 5 pts (4 in DP, 1 in D) experienced major (>1L) intraoperative bleeding. Major post-operative morbidity was reported in 2 DP pts, which included empyema and pulmonary edema. There were 2 toxic deaths, both in DP; 1 intraoperative bleeding and 1 empyema. Efficacy endpoints are summarized in the table. P-N2 was documented in 8/39 (DP) and 9/35 (D) of the operated pts. Conclusions: These results suggest that platinum-based doublet is superior in resection rate and short-term DFS and thus should be selected as optimal preoperative Cx for future phase III trials. No significant financial relationships to disclose.
Effects of statin, aspirin, or metformin use on recurrence free and overall survival in patients with biliary tract cancer (BTC).
Authors: Mairead Geraldine McNamara, Priya Aneja, Lisa W Le, Anne M Horgan, Elizabeth McKeever, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2014)

303 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Statins, aspirin and metformin may have antineoplastic properties. The impact of their use on overall survival and the recurrence free survival of patients who had curative resection of BTC has not been evaluated. Methods: Baseline demographics and use of statins, aspirin or metformin at diagnosis were evaluated in 913 patients with BTC from 01/87 - 07/13 treated at Princess Margaret Cancer Center, Toronto. Their prognostic significance for recurrence free and overall survival was determined using a Cox proportional hazards model. Results: The median age at diagnosis for the entire cohort was 65.7 years (range 23.7-93.7). 795 patients had a performance status &lt; 2 and 461 (50.5%) were male. The primary site was GBC in 310 (34%) patients, DBD in 212 (23%), IHC in 200 (22%) and hilar in 191 (21%). Curative surgical resection was performed in 355 (39%) patients. Among the entire cohort of 913 patients, 151 (16.5%) reported statin use at diagnosis. Atorvastatin was the statin used in 55% of patients. 146 (16%) reported aspirin use and 81 (9%) reported metformin use at diagnosis. Age (p=0.05, p&lt;0.01), and stage (p&lt;0.001, p&lt;0.001) were prognostic on multivariable analysis for recurrence free and overall survival respectively. GBC (p=0.01), DBD (p&lt;0.01) primary and performance status ≥ 2 (p &lt; 0.0001) were also prognostic for overall survival. Recurrence free and overall survival among statin users and nonusers was similar (Hazard Ratio (HR) 1.07, 95% confidence interval (CI) 0.78-1.48, p=0.68) and (HR 0.84 (95% CI 0.67-1.05, p=0.12) respectively. Recurrence free and overall survival among aspirin users and nonusers was similar (HR 0.91, 95% CI 0.64-1.29, P=0.58) and (HR 0.98 (95% CI 0.80-1.22, P=0.88) respectively. Recurrence free and overall survival among metformin users and nonusers was also similar (HR 0.71, 95% CI 0.43-1.17, p=0.18) and (HR 0.81 (95% CI 0.60-1.08, p=0.14) respectively. Conclusions: In this large retrospective cohort of BTC patients, statin, aspirin or metformin use was not associated with improved recurrence free or overall survival.
The risk of debilitating falls in Manitobans living with prostate cancer (pc).
Authors: Joel Roger Gingerich, Pascal Lambert, Malcolm Doupe, Paul Joseph Daeninck, Marshall W. Pitz, Piotr Czaykowski, Alison Bertram-Farough
Journal: Journal of Clinical Oncology (2013)

244 Background: Falls and fall-related injuries are important patient safety problems. Some studies suggest that pc patients have higher fall rates, however the severity of these falls is unknown. We sought to measure if pc patients are at increased risk of a debilitating fall requiring hospitalization. Methods: This is a retrospective population-based study utilizing the Manitoba Cancer Registry and Manitoba Health administrative databases. Our cohort consists of all community-dwelling patients living in Manitoba Canada who were diagnosed with pc between 2004 and 2008. These individuals were matched by age, sex, and time of diagnosis with up to three cancer-free controls. Debilitating falls were defined as falls/fractures requiring hospitalization and were identified using ICD-9 and -10 billing codes. A competing risk model was used to compare debilitating falls between the pc and cancer-free cohorts and expressed as sub-hazard ratios. Follow-up ended December 31, 2009. Results: 2,903 pc patients were identified along with 8,686 matched controls. The mean age was 69.3 and 68.8 respectively. The median follow-up was 3.05 years. Debilitating falls were identified in 109 patients (3.8%) with pc and 345 (4%) matched controls. The cumulative incidence of debilitating falls for those with pc vs cancer-free controls were: 1.08% vs. 1.13% at 1-year and 5.25% vs. 5.96% at five years of follow-up (SHR = 0.95, 95% CI = 0.77 – 1.18, p = 0.65). On univariate analysis, patients with stage IV pc were at higher risk of falls compared to matched controls. This difference was not significant on multivariate analysis though (SHR = 1.19, 95% CI = 0.74 – 1.89, p = 0.48). On multivariate analysis, patients with a Gleason score of ≤6 experienced a reduced risk of debilitating falls compared to matched controls (SHR = 0.44, 95% CI = 0.27 – 0.72, p = 0.001), whereas patients with other Gleason scores did not. The analysis was similar when patients with fractures were excluded. Conclusions: In this large population-based study, the 1- and 5-year cumulative incidence of debilitating falls did not differ significantly for patients with vs without pc. In fact, compared to matched controls, low grade pc patients were less likely to experience a debilitating fall.