tbuckley/cabot-search huggingface dataset:
Head and neck cancer in the elderly: Survival and toxicity with biochemoradiation therapy.
Authors: Lara Iglesias, Beatriz Castelo, Ruth Alvarez, Silvia Garcia Adrian, Juan A. Núñez, Ismael Ghanem, Alberto San Juan del Moral, Asuncion Diaz Serrano, Andrés Redondo, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2014)

e17054 Background: There is an increasing number of older patients diagnosed of locally advanced head and neck cancer (LA-HNC) due to the growing life expectancy. The aim of this study is to assess the suitability of bio-chemoradiation therapy (BCRT) for these patients (Pt). Methods: This multicenter retrospective study was performed in three Spanish hospitals. LA-HNC Pt ≥ 70 years (ys) treated between 2009 and 2011 were included. Demographics, comorbidity, treatment strategies and mortality were recorded. Results: Fifty-two Pt were studied (median age, 74.1 ys; range, 70-88; male, 69%; ECOG PS 0-1, 90.4%; stage IVA/IVB, 71%; recurrent disease, 13.5%). Fifty percent of subjects had ≥ 2 comorbidities (hypertension 52%; diabetes 19%; myocardial ischemia 14%; bronchopathy 37%, chronic renal insufficiency 31%, hepatopathy 6%). Primary tumor site was: oral cavity 35%; larynx 33%; oropharynx 19%; others 13%. Most of the aged (75%) were treated with radical concomitant BCRT (19% of them had received induction chemotherapy); 25% underwent surgery with adjuvant CRT. Table shows schedules of BCRT and most important adverse events. The majority was able to complete all planned treatment (85% radiotherapy; 77% CT). Complete and partial responses rates were 62% and 28% respectively. Number of comorbidities did not influence the election of BCRT. Nevertheless, ECOG PS ≥ 2 and age > 80 ys were related with cetuximab preference. There were 26 deaths: 17 from neoplasia, 1 from treatment complications (pneumonia). At 23 months' follow-up, 16 relapses and 5 second neoplasms were observed; 50% of the Pt were alive (median overall survival 37 m). Conclusions: Elderly Pt with LA-HNC benefit from radical multidisciplinary treatment. We still have to improve the rate of treatment compliance and reduce the toxicities, including a better election of BCRT schedule, taking into account comorbidities, PS and special needs (social, nutritional…) of this group of Pt. CT schedules N % Cetuximab 32 61.5 Cisplatin (3w) 13 25.0 Others 7 13.5 Acute toxicities N % Hematologic ≥3 6 11.5 Mucositis ≥3 16 30.7 Rash ≥3 5 9.6 Rt epithelitis ≥3 8 15.4 Infections 9 17.3 Renal failure 6 11.5 Admission to hospital 15 28.8
Phase II randomized study of high-dose interferon alfa-2b (HDI) versus chemotherapy as adjuvant therapy in patients with resected mucosal melanoma.
Authors: Bin Lian, Li Li Mao, Chuan Liang Cui, Zhi Hong Chi, Lu Si, Xi Nan Sheng, Si Ming Li, Bi Xia Tang, Jun Guo
Journal: Journal of Clinical Oncology (2012)

8506 Background: High-dose interferon alfa-2b regimen has been demonstrated as the standard of adjuvant therapy for resected melanoma. But the subgroup of mucosal melanoma seems more aggressive and insensitive to immunotherapy. So we conducted a phase II study (ChiCTR-TRC-11001798) to compare Interferon regimen with chemotherapy as adjuvant therapy for this particular subgroup pts. Methods: Resected mucosal melanoma pts were randomized to observation (Group A) or receive postoperative adjuvant Interferon (IFN) alfa2b 15 MU/m 2 /day for 5 days/week X 4 weeks followed by 9 MU/m 2 three times each week for 48 weeks (Group B), or chemotherapy with temozolomide 200 mg/m 2 d 1-5 + cisplatin 25 mg/m 2 d 1-3 , repeated every 3 Weeks X 6 cycles (Group C). Results: 189 patients were enrolled and 184 patients were eligible for survival analysis. With a median follow-up of 26.8 months, the median RFS for Group A, B and C were 5.4, 9.4 and 20.8 months, respectively (P&lt;0.001). Estimated median OS for Group A, B and C were 21.2, 41.1 and 49.6 months (P&lt;0.001), respectively. Toxicities were generally mild to moderate. Conclusions: Chemotherapy significantly improved RFS and OS as adjuvant therapy for mucosal melanoma pts over HDI regimen or observation. This trial suggests that different subgroup of melanoma may need different adjuvant therapy.
Metastasectomy for melanoma in the VATS era
Authors: A. Bhargava, M. J. Schuchert, D. O. Wilson, R. J. Landreneau, J. D. Luketich, N. A. Christie
Journal: Journal of Clinical Oncology (2009)

e20001 Background: The role for metastasectomy in the setting of metastatic melanoma remains ill-defined. The aim of this study is to evaluate resection of limited metastases in the setting of melanoma comparing VATS and open approaches, specifically looking at perioperative morbidity and survival. Methods: All patients undergoing metastasectomy for melanoma with curative intent between January 1, 2001 and September 30, 2007 were included. Data was collected retrospectively from the UPMC tumor registry and chart review. Differences between groups were compared with the student's t-test. Results: Of 43 patients undergoing metastasectomy for melanoma, 31 patients were resected with intent to cure (16 VATS, 15 open). Complications were similar between the VATS (12%) and open (13%) groups. There were no perioperative deaths in either group. The median survival in the VATS group was 20.7 months, compared to 26.5 months in the open group (p = 0.17). Importantly, the VATS patients more frequently underwent resection of smaller, peripheral lesions via wedge resection (81%) and only 2 patients (13%) underwent lobectomy. Conversely, patients undergoing open procedures were more likely to have larger, more central lesions and undergo anatomic resections. There were 9 (60%) lobectomies, 3 (20%) segmentectomies 1 (7%) en bloc resection and only 2 (13%) wedge resections in the open group. Conclusions: Metastasectomy for metastatic melanoma in the thoracic cavity can be performed safely by a VATS or open approach. The two approaches have comparable morbidity, mortality and survival outcomes. Careful patient resection remains the hallmark of care in identifying appropriate candidates for metastasectomy. In the setting of patients with short life-expectancy, it may be advantageous to employ a VATS approach when possible to preserve quality of life while achieving similar oncologic outcomes to open procedures. Individuals with a radiographic indication of limited peripheral disease should be considered for a VATS approach to resection of melanoma metastases. No significant financial relationships to disclose.
Low-level laser therapy for chemotherapy-induced peripheral neuropathy.
Authors: John Muzi Lee, Regan M. Look, Crystal Turner, Stuart K Gardiner, Terry Wagie, Jeremy Douglas, Leslie Sorenson, Laura Evans, Sandra Kirchner, Cyd Dashkoff, Karen Garrett, Nathalie Johnson
Journal: Journal of Clinical Oncology (2012)

9019 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common and serious side effect from chemotherapy agents. Low-level laser light therapy (LLLT) devices were approved in 2002 for pain management. Studies suggest a local release of serotonin, increased mitochondrial ATP production, or anti-inflammatory effects as a mechanism of action. We then questioned whether LLLT would show efficacy in mitigating symptoms caused by CIPN. Methods: In a single center prospective randomized trial, participants were randomized to receive either treatment with LLLT twice a week for 8 weeks or placebo LLLT twice a week for 4 weeks followed by actual treatment twice a week for 4 weeks. FACT/GOG-NTX, Brief Pain Inventory (BPI -Severity and Interference), SF-36 Quality of Life (Physical and Mental Score), monofilament and function testing (buttoning, coin use and walking) were conducted prior to initiation of therapy, during, at completion, and 2 months after treatment. 20 participants, 16 women and 4 men (average age 58 and 63 respectively), were enrolled between October 2009 and June 2010. 10 patients were randomized to each group. Average time from end of chemotherapy to enrollment was 32.6 months (range 2 - 120 mo). All patients had neuropathic involvement of the feet. 14 patients had additional involvement of the hands. Results: Compared to baseline, patients receiving any amount of active treatment showed significant improvement at 8 weeks in NTX, BPI, function testing, and SF36 Mental score. Those receiving 4 weeks of placebo treatment showed improvement in only BPI, NTX and SF36 Mental score. At 2-month follow up, all 20 patients showed a significant improvement in walking and SF 36 mental score, suggesting 4 weeks of active treatment improved function. No significant difference in monofilament testing was observed throughout the study in either group. Direct comparison between 4 or 8 weeks of treatment vs. placebo showed a statistically significant difference in walking function at 2-months. All patients tolerated therapy well without side effects. Conclusions: Low-level laser light therapy improved functional test over placebo and may be a viable option for non-medical management of CIPN. Further study of LLLT in CIPN is warranted.
Screening for Celiac Disease
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, Mark Ebell, John W. Epling, Jessica Herzstein, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, Maureen G. Phipps, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng
Journal: JAMA (2017)

<h3>Importance</h3> Celiac disease is caused by an immune response in persons who are genetically susceptible to dietary gluten, a protein complex found in wheat, rye, and barley. Ingestion of gluten by persons with celiac disease causes immune-mediated inflammatory damage to the small intestine. <h3>Objective</h3> To issue a new US Preventive Services Task Force (USPSTF) recommendation on screening for celiac disease. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the accuracy of screening in asymptomatic adults, adolescents, and children; the potential benefits and harms of screening vs not screening and targeted vs universal screening; and the benefits and harms of treatment of screen-detected celiac disease. The USPSTF also reviewed contextual information on the prevalence of celiac disease among patients without obvious symptoms and the natural history of subclinical celiac disease. <h3>Findings</h3> The USPSTF found inadequate evidence on the accuracy of screening for celiac disease, the potential benefits and harms of screening vs not screening or targeted vs universal screening, and the potential benefits and harms of treatment of screen-detected celiac disease. <h3>Conclusions and Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. (I statement)
Concurrent chemotherapy and high intensity focused ultrasound treatment for patients with local advanced pancreatic cancer or metastatic pancreatic cancer: A retrospective study.
Authors: Hong Shen, Hu Xiaoye, Chen Tianzhou
Journal: Journal of Clinical Oncology (2014)

e15242 Background: To compare the safety and efficacy of concurrent chemotherapy with or without high intensity focused ultrasound (HIFU) in patients with local advanced pancreatic cancer or metastatic Pancreatic Cancer. Methods: A total of 498 patients were included from October 2002 to November 2013. 248 patients were treated with concurrent chemotherapy with HIFU, including 152 male and 96 female patients, aging from 31-91 years, the mean age was 65 years. 203 patients was diagnosed with metastatic pancreatic cancer, 45 patients with local advanced pancreatic cancer; 250 patients were treated with chemotherapy, including 144 male and 106 female patients, aging from 28-88 years, the mean age was 65 years. 212 patients was diagnosed metastatic pancreatic cancer, 38 patients with local advanced pancreatic cancer. Results: Objective response rate was 22.6%(56/248) in concurrent chemotherapy with HIFU group and 16.0%(40/250) in chemotherapy group, disease control rate was 75.8%(188/248) in concurrent chemotherapy with HIFU group and 69.2%(173/250) in chemotherapy group respectively. No significant differences in overall survival(OS;8.67 vs 7.9 months,P>0.05) between the concurrent chemotherapy with HIFU and chemotherapy groups were found in the overall population. There were no severe complications or adverse events related to concurrent chemotherapy with or without HIFU in any of the patients treated. Conclusions: Although this study may have limitations, preliminary results demonstrate the safety of clinical application of HIFU concurrent with chemotherapy for pancreatic cancer and reveal it to be a promising mode of treatment for local advanced pancreatic cancers.
Molecular profiling of pancreatic adenocarcinoma to identify targeted therapeutic options in patients who have undergone pancreaticoduodenectomy.
Authors: Erin H Baker, Mike Fruscione, Allyson Cochran, Sherri Z. Millis, John B Martinie, Ryan Z Swan, David A Iannitti
Journal: Journal of Clinical Oncology (2015)

e15232 Background: Pancreatic adenocarcinoma (PAC) is associated with poor overall 5 year survival. Targeted chemotherapeutic treatment options may offer an opportunity to impact the clinical course of PAC. We review the chemotherapeutic treatment of patients who underwent surgical resection by pancreaticoduodenectomy (PD) relative to agents with associated benefit or lack of benefit by tumor molecular profiling (MP) technology. Methods: Retrospective analysis of 37 patients who underwent PD for PAC included operative details, MP - Sanger or next generation sequencing, protein expression (immunohistochemistry), and/or gene amplification (CISH or FISH), and treatments. Patients’ neoadjuvant and adjuvant chemotherapeutic treatment agents were reviewed relative to MP analysis. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan Meier curves. Results: 37 patients were analyzed. Mean age was 67.9 years, mean BMI was 25.9kg/m2; 49% were male. Final pathologic stage was T3 N1 (IIB by AJCC TNM) in 73%. 8 patients (21.6%) received neoadjuvant chemotherapy, and 27 (73.0%) received adjuvant chemotherapy following PD. Chemotherapeutic agents most frequently associated with benefit by MP were fluorouracil, capecitabine, pemetrexed (n = 31), gemcitabine (gem; n = 31), and nab-paclitaxel (n = 22). OS was 550 days and DFS was 325 days. 3 patients were RRM1 positive (predictive for lack of response to gem), response to gem was lower than RRM1 negative patients. The 31 RRM1 negative patients survived ~3 times longer. KRAS mutations (MT) were detected in 79.4% and p53 MT in 57.1% of patients tested. Patients with KRAS MT lived longer than patients who were KRAS wild type; co-incidence of other biomarkers and treatments was not evaluated. Conclusions: Decreased OS of the 3 RRM1 positive patients treated with gem, associated with lack of benefit by MP, is consistent with previous reports showing this marker is predictive of gem response. Based on the trend in this limited dataset, KRAS MT PAC patients may have a survival benefit; further analysis of these patients’ MP will be useful to identify potential confounding factors.
Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) expression in primary breast cancer (BC); correlations with clinical characteristics and patient outcomes.
Authors: Neelima Vidula, Christina Yau, Andrei Goga, Hope S. Rugo
Journal: Journal of Clinical Oncology (2015)

1090 Background: The interaction of the PD-1 receptor on tumor infiltrating lymphocytes and PD-L1 on tumor cells dampens antitumor immunity. Two phase I trials suggested efficacy of anti-PD-1/PD-L1 antibodies in triple negative (TN) BC. This study investigated associations between primary BC PD-1 and PD-L1 expression, clinical characteristics, and patient outcomes in publically available databases. Methods: We evaluated PD-1 and PD-L1 expression using microarray data from the neoadjuvant I-SPY 1 study (n = 149). Associations with clinical features and chemotherapy response were assessed by Kruskal-Wallis and Wilcoxon rank sum tests, respectively. Recurrence free survival (RFS) associations were assessed by the Cox proportional hazard model. Pearson correlations between PD-1 and expression of PD-L1, HAVCR2, STAT5A, FOXP3, MYC, and ESR1 were determined in I-SPY 1 and 2 other datasets: METABRIC (n = 1992) and TCGA (n = 817). Results: In I-SPY 1, PD-1 expression was significantly higher in HER2+ and TNBC (p = 0.003), and in grade 2/3 tumors (p = 0.043); this association was also seen in METABRIC. PD-1 expression was associated with pathologic complete response (p = 0.006) but not with tumor stage, nodal status, lymphovascular invasion or RFS. While PD-L1 did not correlate with tumor features, patients with PD-L1 expression in the lowest quintile had worse RFS, even after subtype adjustment (HR 2.33, p = 0.01). In all 3 datasets, PD-1 significantly correlated with PD-L1, HAVCR2, and STAT5A, and inversely with ESR1. In the TN subset of TCGA and METABRIC, PD-1 significantly correlated with PD-L1, HAVCR2, and STAT5A. In TCGA and METABRIC, PD-L1 significantly correlated with HAVCR2 and STAT5A, and this was also seen in the TN subset. In TCGA alone, PD-1 and PD-L1 significantly correlated with FOXP3, and PD-1 with MYC. Conclusions: PD-1 expression is higher in TN and other aggressive BC subtypes. PD-1 and PD-L1 correlate with immune related genes HAVCR2 and STAT5A. Low PD-L1 expression may be an adverse prognostic factor. Trials are underway to investigate the activity of anti-PD-1/PD-L1 antibodies in TNBC and to elucidate markers of response.
Oncogenic mutations in colorectal cancer, indications for anatomical sites, and targeted intervention.
Authors: Giovanni Corso, Valeria Pascale, Giuseppe Flauti, Daniele Marrelli, Franco Roviello
Journal: Journal of Clinical Oncology (2013)

e22037 Background: Oncogenic mutations, such as KRAS, in colorectal cancer patients are considered standard molecular biomarkers that predict the clinical benefit for the targeted intervention with EGFR inhibitors. In addition, these mutations are associated with specific anatomical area in the colon tumor development, as BRAF mutations with the microsatellite instability. Methods: In this translational study we aim to assess the mutation frequencies of the EGFR [hotspot area and polyadenine deletions (A13_del)], KRAS, BRAF V600E , and PIK3CA oncogenes in a series of 280 colorectal cancer patients. Microsatellite instability phenotype is considered in this series. All patients' clinicopathological data were considered for statistical analysis and associations. Results: In this study, we verified multiple associations between oncogenic mutations and specified clinicopathological tumor features. Respectively, we identified the following significant results: 1) EGFR A13_deletions are associated with right colon carcinoma (22.2% vs. 3.3%; p&lt;0.005), mucinous histotype (16% vs. 7.8%; p=0.042), G3 grading (19% vs. 7.3%; p=0.024) and microsatellite instability status (p&lt;0.005); 2) PIK3CA mutations are related mucinous histotype (12% vs. 4.4%; p=0.021) 3) KRAS G12 and KRAS G13 mutations are correlated respectively with the left (91.4% vs. 59.3%) and right (40.7% vs. 8.6%) colon cancer development (p&lt;0.005), and finally 4) microsatellite instability is associated with right colon tumors (28.4% vs. 5.5%; p&lt;0.005). Conclusions: Mostly, we verified a high frequency rate of the KRAS G13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRAS G12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right colon cancer is associated with specific molecular characteristics, in comparison to left colon tumors. These evidences, in association with specific clinicopathological data, can delineate novel approaches for the colorectal cancer classification and targeted intervention.
A national platform for molecular diagnostics: Results of the Cancer Research U.K. Stratified Medicine Programme.
Authors: Emily Shaw, Rachel Butler, David Gonzalez de Castro, Michael Griffiths, Andrew Hanby, Jane Hair, Frances Rae, Jane Rogan, Dion Morton, James Brenton, John D. Chester, Stephen R. D. Johnston, Ian Walker, Peter W. M. Johnson
Journal: Journal of Clinical Oncology (2014)

11079 Background: Increasing demand for testing multiple markers for targeted therapies requires a platform to incorporate molecular diagnostics in the normal pathway of care. This programme was planned to demonstrate the applicability of a nationwide platform of testing, linked to healthcare records in a central database. Methods: From 8/2011 to 6/2013, patients with breast, colorectal, prostate, lung or ovarian cancer, or melanoma, were approached at 26 hospitals for consent to centralised molecular testing of routine biopsies. Formalin-fixed paraffin-embedded sections were forwarded with peripheral blood samples to 3 technical hubs for analysis of a small panel of abnormalities by Sanger sequencing, pyrosequencing or similar mathods, and fluorescent in-situ hybridisation for chromosomal structural changes. Results were transmitted directly to clinical centers for inclusion in medical records. A routine clinical dataset was collected from all patients using the national cancer registration system. Results: 10,754 patients (98% of those approached) consented to analysis of material, with 9010 samples sent for analysis. Of 1,889 lung cancers, 35% had at least one abnormality, only 0.65% had more than one. kRAS was most often mutated (26%), followed by EGFR (8.3%), Alk rearrangement (1.9%) and BRAF (1%). In 1634 colorectal cancers, 47% had one abnormality, 30% two and 3% three. Commonest abnormalities were mutated TP53 (25%), double mutated TP53 and kRAS ( 17%), kRAS only (17%) and BRAF (5%). In 535 melanomas there were 42% BRAF mutants, 22% NRAS mutant and only 2.4% with double abnormalities. There was heterogeneity between the laboratories in turnaround time and failure rate, especially for non-standard analyses. A multiplex next-generation sequencing (NGS) panel was piloted for samples collected in the last 3 months of the programme, showing high levels of concordance in comparison to conventional sequencing. Conclusions: A broad system of molecular diagnostics is feasible and highly acceptable to patients. The efficiency is improved with NGS analysis, and the system is now being used to support prescreening of patients with lung cancer for entry into a multiarm study of novel therapeutics.