tbuckley/cabot-search huggingface dataset:
Short and long-term survival in metastatic pancreatic adenocarcinoma, 1993-2013.
Authors: Talia Golan, Tal Sela, Ofer Margalit, Uri Amit, Naama Halpern, Dan Aderka, Einat Shacham Shmueli, Damian Urban, Yaacov Richard Lawrence
Journal: Journal of Clinical Oncology (2017)

232 Background: Over the previous two decades several new agents have been approved for the treatment of metastatic pancreatic cancer (mPDAC). Their efficacy was demonstrated amongst highly selected patients that participate in randomized phase III trials, hence it is not clear to what extent these advances are reflected within the broader mPDAC population. We performed a population-based survival analysis of newly diagnosed patients who presented with mPDAC. Methods: Survival statistics were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed with mPDAC between 1993-2013. Demographic variables collected included age, gender, race, and marital status. Tumor characteristics collected included location and grade. Survival was analyzed using the Kaplan-Meier method and proportional hazard models as appropriate. Exclusion criteria included diagnosis at autopsy, unknown histology and pancreatic neuroendocrine tumors. Results: The study population consisted of 57,263 patients diagnosed with mPDAC from 1993-2013, 52% male, median age 69 years (range 15-104). Prognosis correlated with age, gender, race, marital status, tumor location, grade and year of diagnosis. Median overall survival (OS) stayed stable at 2 months between 1993 and 2013. Improvements in OS were seen for all patients, but especially for younger patients ( &lt; 50 years of age) and more recent year of diagnosis group (2009-2013). The percentage of patients who died within two months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%, p &lt; 0.0001). The subgroup of patients achieving longer-term survival has increased, with 12-month survival improving from 4.9 % to 12.7% (p &lt; 0.0001) between 1993 and 2013. Conclusions: There has been a continuous but modest improvement in OS of patients diagnosed with mPDAC between 1993 and 2013. The percentage of patients living beyond one year has significantly increased over time; however the percentage of patients dying within 2 months has only slightly decreased.
Biweekly cisplatin (C) and gemcitabine (G) in patients (pts) with advanced biliary tract cancer (ABTC): A retrospective analysis.
Authors: Daniel H. Ahn, Josh Reardon, Chul Ahn, Manojkumar Bupathi, Kristen Keon Ciombor, Christina Sing-Ying Wu, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2017)

434 Background: Based on the ABC 02 trial, standard therapy for ABTC is CG for up to 8 cycles. However, a recent abstract (Doherty et al, ASCO 2016) confirmed that a cohort of pts does benefit from continued therapy. The weekly administration of G and C can add significant toxicities that may prohibit prolonged treatment (trmt). Previous studies have shown that a biweekly schedule (Ko AH et al JCO 2012) of fixed dose rate (FDR) G helps optimize the prescribed regimen with an improved toxicity profile and added convenience to pts while maintaining efficacy. Methods: Pts with ABTC treated with FDR G (1000mg/m 2 at 10mg/m 2 /min) with C 20mg/m 2 (GC) on days 1 and 15 of every 28-day cycle were included for analysis. Pts received trmt until time of progression. Data was collected including demographics, clinico-pathologic features, toxicities and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). Results: The study included 109 evaluable pts with ABTC who received CG. Pts had disease that was locally advanced (16.5%) or metastatic (83.5%). Median age was 60 years (28-86). Sites of tumor included gallbladder (21.1%), ampullary (3.6%) and bile duct (75.2%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade 3 or 4 adverse events included neutropenia (11%), fatigue (10%), thrombocytopenia (TCP) (6.4%), anemia (2.8%), and abnormal liver function tests (2.8%). Fifty-two percent of pts received second line therapy. Conclusions: Biweekly CG in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many. Further prospective exploration should consider evaluating the role of biweekly gemcitabine and cisplatin regimen in ABTC especially as a potentially more favorable platform to combine with novel agents. [Table: see text]
Short-term outcomes of laparoscopic D2 gastrectomy with complete mesogastrium excision (D2+CME) for advanced gastric cancer.
Authors: Daxing Xie, Jianping Gong
Journal: Journal of Clinical Oncology (2017)

43 Background: D2 lymphadenectomy has been widely accepted as a standard procedure of surgical treatment for local advanced gastric cancer [1,2]. However, neither the dissection boundary nor the extent of the excision for perigastric soft tissues has been described [3-7]. Our previous researches demonstrate the existence of disseminated cancer cells in the mesogastrium [8, 9] and present an understandable mesogastrium model for gastrectomy [10]. Hence, the D2 lymphadenectomy plus complete mesogastrium excision (D2+CME) is firstly proposed in this study, aiming to assess the safety, feasibility and corresponding short-term surgical outcomes. Methods: All of these patients underwent laparoscopy assisted D2+CME radical gastrectomy with a curative R0 resection, and all the operation was performed by Prof. Jianping Gong, chief of GI surgery of Tongji Hospital, Huazhong University of Science and Technology. All participants provided informed written consent to participate in the study. This study was approved by the Tongji Hospital Ethics Committee. The standard surgical procedures in the video are described as follows. Reconstruction of the alimentary tract was done by extracorporeal anastomosis. Standard recovery protocols were followed in postoperative treatments. Results: 68 patients between September 2014 and March 2016 have been recruited with informed consent and underwent laparoscopic D2+CME by a single surgeon. The mean number of retrieved regional lymph nodes was 33.62±11.40 (ranges 14-55). The mean volume of blood loss was 12.44±22.89 ml (ranges 5-100). The mean laparoscopic surgery time was 127.82±17.63 mins (ranges 110-165). The mean hospitalization time was 16.5±3.3 days (ranges 8-28). No operative complication was observed during the hospitalization. Conclusions: The anatomical boundary of mesogastrium is well described and dissected within D2+CME surgical process. It proves to be safely feasible and repeatable with less blood lost, qualified lymph nodes, retrieval results, and other improved short-term surgical outcomes in advanced gastric cancer. Meanwhile, potential disseminated cancer cells fall into the mesogastrium can be eradicated by D2+CME. Clinical trial information: NCT01978444.
A retrospective study of the brachial plexus MPNSTs.
Authors: Lin Chen, Cong Yu, Yu-dong Gu, jian-Yun Yang
Journal: Journal of Clinical Oncology (2014)

e21515 Background: Malignant peripheral nerve sheath tumors (MPNSTs) of upper extremity are rare, especially at brachial plexus, and most publications are case reports or with few patients. The aim of this study is to present our experience to treatment of brachial plexus MPNSTs. Methods: A retrospective study of 15 patients, who were diagnosed brachial plexus MPNSTs from 2008 to 2012, was performed. The clinical data, treatments characteristics, and prognosis were reviewed. Results: The median age of our study population was 42 years, range from 25 to 80 years. 6 of them were female and 9 were male. According to functions of the aggressive nerves, the patients appeared with different symptoms at different locations. Numbers of function lesion in different location (hand, forearm, arm, axillary, neck) were 2, 4, 2, 2, 5, respectively. All of 15 patients underwent surgical treatment, 7 patients with adjuvant treatments (46.7%). During follow up, rate of recurrence of all patients was 46.7%. 28.6% of recurrence in the patients who accepted adjuvant treatment compared with 62.5% of recurrence in those who were not accepted adjuvant treatment. Conclusions: MPNSTs of brachial plexus are rare in peripheral nerve tumors. They have high recurrence rates and poor prognoses. The mainstay therapy for MPNST is surgical resection. Aggressive surgical resection to achieve negative margins combined with adjuvant treatment can achieve a better local control.
Analysis of the intratumoral heterogeneity of PIK3CA mutant alleles in breast cancer (BC): Implications for the luminal (LUM) phenotype.
Authors: Leticia De Mattos-Arruda, Javier Cortes, Claudia Aura, Mafalda Oliveira, Alejandro Navarro, Ginevra Caratu, Alex Sanchez-Pla, Josep Gregori, Cristina Saura, Josep Tabernero, Joan Seoane, Ana Vivancos
Journal: Journal of Clinical Oncology (2012)

10511 Background: The hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway may confer endocrine therapy resistance and is an attractive target for LUM patients (pts). However, PI3KCA mutations could be heterogeneously distributed within the tumor as different genetic clones and this could have therapeutic implications. Our aim was to assess the frequency of PIK3CA mutant alleles in different BC phenotypes. Methods: DNA was obtained from 75 consecutive BC FFPE samples and was profiled with the OncoCarta Panel v1.0 (Sequenom). Frequencies of mutant alleles (% mutant allele, mA) of PIK3CA mutations were extracted from the MassARRAY spectrum data. The viable tumor area (TA) was scored by H&amp;E. Pts were stratified by BC phenotypes: ER+/HER2- (LUM); HER2+ (HER2); triple negative (TN). Results: 25.3% of pts had PIK3CA mutations. The mean PIK3CA mA (p=0.04) and mean TA (p=0.07) differed among phenotypes. LUM tumors demonstrated greater frequencies of PIK3CA mutation (38% vs.15%, p=0.05) and mean PIK3CA mA (31% vs.17%, p=0.01) than non-LUM.There was a significant linear correlation between mA and TAfor LUM tumors (r=0.91); when HER2 and TN tumors were also considered this relation was less pronounced (r=0.66). Overall, LUM pts, median age 55 (42-84), had significantly better clinical outcomes (p=0.00024), whilst analyses of prognosis did not differ among LUM pts (PIK3CA mutant vs. wild-type, p=0.68) nor mutant pts (LUM vs. non-LUM, p=0.36). Outcomes will be presented. To assess the intratumoral heterogeneity of PIK3CA mutations, we determined the mA/TA ratio. The mA/TA ratio should be 0.5 for a homogeneous distribution of the heterozygous PIK3CA mutation. The ratio of LUM patients was close to 0.5, while for non-LUM it was lower, suggesting a non-homogeneous distribution of PIK3CA mutant alleles in non-LUM tumors. Conclusions: Our analysis indicates that LUM tumors tend to be homogeneous regarding PIK3CA mutation as compared to HER2 and TN. This suggests that PIK3CA oncogenic activation could be an early hit for tumor initiation in LUM tumors, which could be more specifically targetable; thus, pts would derive greater benefit from PI3K-inhibitors plus hormonal therapy.
Randomized phase III trial in extensive-disease small cell lung cancer comparing first-line etoposide to topotecan in combination with platinum.
Authors: Morten Mau-Soerensen, Olfred Hansen, Bente Holm, Christa Haugaard Nyhus, Tine McCulloch, Henrik Anker Nielsen, Kim Wedervang, Carsten Rytter, Nina Jeppesen, Seppo Langer
Journal: Journal of Clinical Oncology (2014)

7519 Background: Randomized trials in extensive disease (ED) small cell lung cancer (SCLC) comparing the camptothecins to standard etoposide based chemotherapy have reached conflicting results. Here we report the results of an interim analysis of a phase III trial randomly allocating patients (pts) with ED SCLC to etoposide or topotecan in combination with platinum. Methods: Previously untreated pts with ED SCLC were randomized to six cycles of T (topotecan 2.0 mg/m2 IV, day 1-3; cisplatin 50 mg/m2 IV, day 3) or E (etoposide 120 mg/m2, day 1-3; carboplatin IV AUC = 5, day 1) every 3 weeks. Primary end-point was overall survival (OS) and secondary end-points were response, progression-free survival (PFS), and safety. A sample size of 380 pts was estimated to detect an increase in 2-year survival from 7.5 to 15 % (α=0.05, β=0.20.) ClinicalTrials.gov NCT 00812266. Results: The trial was prematurely stopped due to poor accrual according to a pre-planned interim analysis after the accrual of 281 pts reducing power to 0.66. Prognostic factors were equally balanced between arms. WHO performance status > 2 were recorded in 20.0% and 50% were females. Median age was 64 years (40 – 82). Most frequent grade 3/4 non-hematological adverse events (AEs) were infections (E 17.1 vs T 12.1%) and fatigue (E 14.2 vs T 12.7%). Most common grade 1/2 non-hematological AEs were alopecia (E 91.3 vs T 88.0%), nausea (E 55.9 vs T 57.9%) vomiting (E 27.6 vs T 24.1%), auditory toxicity (E 25.2 vs T 33.8%), and neuropathy (E 33.9 vs T 39.8%). Grade 4 leuco- and thrombocytopenia were observed in 21.1 and 12.8% of pts in arm E, respectively, compared to 6.7 and 5.2% in arm T (p < 0.01). Overall response rates were 69.1 % in arm E compared to 59.8% in arm T (NS). Median PFS was 6.6 months in E arm and 6.9 month in arm T, HR = 0.93, 95% CI 0.72-1.19, p=0.55. Median OS and 2-yr survival rates were 10.9 months and 9.2% in arm T, compared to 9.8 months and 8.7% in arm E, respectively, HR = 0.87, 95% CI 0.67-1.17, p=0.26. Conclusions: No differences in OS or PFS were observed comparing first line E with T in ED SCLC. Significantly more hematological toxicity was noted in the E arm. A biomarker study is planned to identify pts that derive most benefit from either T or E. Clinical trial information: NCT00812266.
Dosing of chemotherapy for solid tumors based on ideal body weight versus actual body weight: Review of a military oncology clinic’s practice.
Authors: Lonnie D. Miller, Aaron Henderson, Nicole Vietor, Benjamin Jacob George
Journal: Journal of Clinical Oncology (2013)

e17575 Background: Dose-reductions or “capping” of the body surface area (BSA) at 2.0m 2 for chemotherapy due to obesity has been widely practiced throughout oncology due to the concerns about AE in obese patients. In 2012 ASCO published guidelines recommending that full weight-based dosing of chemotherapy be used. This retrospective review was undertaken to evaluate the dosing practices at a major U.S. Army oncology clinic. Methods: Retrospective, random sampling of patients with breast, lung, gastrointestinal and testicular cancer and lymphoma treated at a tertiary military medical center within the last three years. Basic demographic data, cancer type, stage, actual and ideal BSA , incidence of dose-reduction, hematologic data before and after cycle 1, incidence of grade 3-4 toxicity and use of granulocyte-colony stimulating factor was recorded. Results: 231 patients (61.9% female, 38.1% male) were included in the analysis (breast 36.4%, lung 19.5%, GI 21.2%, testicular 6.5%, lymphoma 16.5%). The majority of patients were white, 70.6%, with asian, black, hispanic and other making up 2.6%, 13.4%, 1.7% and 11.7% respectively. Seventy-eight had a BSA &gt;2.0m 2 . No incidences of dose-reduction were identified. Analysis did not show a correlation between differences in actual vs. ideal BSA and toxicity. When other variables were considered, there was a statistically significant inverse relationship between age and grade 3-4 toxicity (p=0.02) although this was deemed clinically insignificant (coefficient of determination &lt;0.25). Conclusions: In a retrospective review of chemotherapy dosing practices in a major military medical center, we found no cases of dose-reduction based on obesity. There was also no significant increased toxicity when patients were dosed according to actual vs ideal body weight in keeping with previously published literature. There was a significant inverse relationship between age and grade 3-4 hematologic toxicity.
A large prospective trial of children with unilateral retinoblastoma with and without histopathologic high-risk features and the role of adjuvant chemotherapy: A Children’s Oncology Group (COG) study.
Authors: Murali M. Chintagumpala, Bryan Langholz, Ralph Eagle, Daniel Albert, Mohammed Javed Ali, Vikas Khetan, Santosh Honavar, Joan O'Brien, Ann Leahey, Katherine K. Matthay, Anna T. Meadows, Patricia Chevez-Barrios
Journal: Journal of Clinical Oncology (2012)

9515 Background: The definition of histopathologic high-risk features (HRF) in enucleated eyes of children with unilateral retinoblastoma and their contribution to metastases is controversial. The COG completed a large, prospective international study to determine the prevalence of strictly defined histopathologic HRF that are predictors of recurrence and the role of chemotherapy to prevent recurrences. Methods: All patients who underwent enucleation for unilateral retinoblastoma were eligible for the study. Pathology slides were submitted for central review within 21 days of enucleation. Patients with evidence of one or more high-risk features (posterior uveal invasion grades IIC and D, concurrent optic nerve and choroid involvement and post-lamina optic nerve involvement) as determined by central review, received 6 cycles of chemotherapy consisting of carboplatin, vincristine and etoposide. All others were observed. All patients were followed for extraocular recurrences. Results: Patients were enrolled from February of 2005 until May 2010. As of July 2011, the median follow-up from enrollment was 1.9 years (max=5.3 years). Of 312 patients with central histopathology review, 49 patients had their risk classification changed (13% with no HRF had HRF, 24% with HRF had no HRF). Two patients developed extraocular disease and one patient died of unknown cause. The death and one of the extraocular relapses occurred among the 93 (2/93=2.2%, upper 95% CI 3.4%) patients assigned by the central review to receive chemotherapy, while one patient experienced extraocular relapse among the 209 (1/209=0.5%, upper 95% CI 0.6%) assigned to observation only. There is no evidence of a difference in the EFS and OS in these two groups. Conclusions: Preliminary results strongly suggest that a central review of pathology can spare a significant number of patients from exposure to chemotherapy. Chemotherapy may have contributed to fewer relapses in patients with high-risk features as defined in this study. The preliminary results from this study indicate an excellent outcome with this approach.
Incidence, characteristics, and survival of patients with <i>EGFR</i>-mutant lung cancers with <i>EGFR T790M</i> at diagnosis identified in the lung cancer mutation consortium (LCMC).
Authors: Mark G. Kris, Geoffrey R. Oxnard, Bruce E. Johnson, Lynne D Berry, Heidi Chen, David J. Kwiatkowski, Anthony John Iafrate, Ignacio Ivan Wistuba, Wilbur A. Franklin, Dara Aisner, Lecia V. Sequist, Fadlo Raja Khuri, Edward B. Garon, William Pao, Charles M. Rudin, Joan H. Schiller, Eric B. Haura, John D. Minna, Paul A. Bunn
Journal: Journal of Clinical Oncology (2013)

8085 Background: Somatic T790M mutations are detected in 62% of EGFR-mutant lung cancers with acquired resistance to EGFR TKIs, and have rarely been identified in the tumor at diagnosis and/or within the germline DNA. Multiplexed genotyping by the LCMC permitted us to evaluate the incidence of T790M at diagnosis, co-mutations, and survival of patients with this driver. Methods: The 14 member LCMC prospectively tested tumors of patients with lung adenocarcinomas in CLIA laboratories for mutations in EGFR and 9 other genes. We assayed T790Mby Sequenom, Snapshot, or Sanger sequencing. Germline DNA was not collected. Results: In the 987 tumors tested, 209 had mutations in EGFR alone: 25 T790M (2.5%) , 157 sensitizing EGFR mutations (exon 19 del, L858R, L861Q, G719X) without T790M, 23 exon 20 ins, 4 other mutations. 13 additional cases harbored mutations in EGFR and another driver; 2 with both T790M and PIK3CA. In each of the 27 EGFR-mutant cases with T790M, a coincident EGFR mutation was detected (18 exon 19 del, 9 L858R, 1 exon 20 ins). EGFR T790M was found more often than EGFR exon 20 ins or mutations in HER2 (1.9%), BRAF (1.6%), or PIK3CA (0.7%). Patients with T790M: 77% women, 81% never smokers, median age 55 (range 38-79), stage IV at diagnosis 81%, PS 0/1 100%. Characteristics did not differ from persons with sensitizing mutations and no T790M. Median survival from the diagnosis of metastatic disease for patients with EGFR-mutant lung cancers was 3.5 yrs with T790Mand 4.0 yrs without (p=0.926). Conclusions: T790M mutations were detected at diagnosis in 3% of adenocarcinomas and always coincident with another EGFR mutation. Cases with T790M represent 13% of all cases of EGFR- mutant lung cancer. Characteristics and survival for patients with EGFR- mutant lung cancers with T790M at diagnosis were similar to individuals with sensitizing mutations and no T790M. The observed incidence of T790M exceeded that of the other actionable targets HER2, BRAF, and PIK3CA. Trials should study this unique population identified by routine multiplexed genotyping. Supported by 1RC2CA148394-01 and the National Lung Cancer Partnership. Clinical trial information: NCT01014286.
The effect of duloxetine on chemotherapy-induced peripheral neuropathy in advanced pancreatic cancer patients receiving gemcitabine plus nab-paclitaxel treatment.
Authors: Hidetaka Suzuki, Akira Shinohara, Izumi Ohno, Shuichi Mitsunaga, Misaki K Takeno, Hideki Funazaki, Gen Kimura, Kazuo Watanabe, Kumiko Umemoto, Mitsuhito Sasaki, Hideaki Takahashi, Hiroshi Imaoka, Yusuke Hashimoto, Masafumi Ikeda, Masakazu Yamaguchi
Journal: Journal of Clinical Oncology (2017)

453 Background: Recently, gemcitabine plus nab-paclitaxel (GN) has come to be used frequently as the first-line chemotherapy for advanced pancreatic cancer. It has been reported that chemotherapy-induced peripheral neuropathy (CIPN) associated with nab-paclitaxel (nab-PTX) may impair the quality of life of the patients, and may, moreover, necessitate dose reduction or early cessation of the chemotherapy, thereby potentially impacting patient survival. However, there are no established treatments against CIPN. Several reports have suggested that duloxetine, which has been proved to be highly effective in managing diabetic peripheral neuropathy, is also effective against CIPN induced by platinum agents and taxanes. The aim of this study was to examine the frequency of nab-PTX related CIPN, its various influences, and the efficacy of duloxetine in the management of CIPN. Methods: Data of 121 pancreatic cancer patients who received GN as first chemotherapy between December 2014 and December 2015 at the National Cancer Center Hospital East, Japan, were analyzed retrospectively. Results: The frequency of CIPN of any grade was 60.3% (73 patients) and that of CIPN of grade ≥ 2 was 21.5% (26 patients). Among the patients who showed CIPN, 34 patients received 20-60 mg of duloxetine once daily, and the remaining patients never received it (no duloxetine group). 18 patients were on duloxetine for more than four weeks (the duloxetine group). 8 patients discontinued duloxetine in less than four weeks because of its side effects, such as, nausea, and somnolence. In the duloxetine group, CIPN was improved in 4 patients, and remained non-progressive in 12 patients. The relative dose intensity (RDI) of nab-PTX since the emergence of CIPN in the duloxetine group was higher than that in the no duloxetine group (63.2 % vs. 48.2 %, p = 0.0046). Conclusions: The frequency of nab-PTX related CIPN at our hospital was almost similar to that of previous reports. The results of this study suggest the possibility that duloxetine not only improves nab-PTX-related CIPN, but delays its progression. Therefore, it might contribute to continuing GN with a high RDI for longer periods of time.