tbuckley/cabot-search huggingface dataset:
Characteristics of chemotherapy-induced peripheral neuropathy in patients with breast cancer.
Authors: Namie Okino Sawada, Alexandra Paola Zandonai
Journal: Journal of Clinical Oncology (2015)

85 Background: In Brazil, breast cancer has the second highest incidence of neoplasms, the most common among women. It is expected there will be 57,120 new cases and a risk 56.09 cases per 100 thousand women. For its treatment, neurotoxic chemotherapeutics that can cause chemotherapy-induced peripheral neuropathy (CIPN) are used. Methods: This is an exploratory descriptive study developed in a cancer treatment reference hospital in the city of Sao Paulo, Brazil. Aim: To search the patients with breast cancer during treatment with neurotoxic agents and evaluate the presence of CIPN with application of Chemotherapy-Induced Peripheral Neuropathy Assessment Tool questionnaire (CIPNAT). Results: The sample was 44 women with a mean age of 52 years (SD = 10.54), 47.7% had local disease, 72.7% were treating with taxanes neurotoxic agents. The main neuropathic symptoms measured at CIPNAT: 75% had motor symptom weakness with an average score for severity of 6.45 causing an average of distress 5.36; 65.9% muscle and joint pain average severity of 6.31 causing an average of 5.59 distress; and 56.8% sensitive symptom numbness in the hands average severity of 4.76 causing an average of 3.52 distress. These symptoms had a negative impact in the activities of daily living (ADL) such as physical exercise (mean score = 5.32), enjoyment of life (mean score = 4.77) and leisure activities (mean score = 4, 03). Although few (13.6%) reported that suffered some injury or accident due to CIPN. Discussion: The results are consistent with those presented in the scientific literature, but measured with other assessment tools such as the NCI CTCAE, WHO and EORTC QLQ-C30 and CIPN20, which also showed that motor disorders (weakness, muscle cramps and loss of strength in the hands) and sensory (numbness and tingling in the hands and feet). Conclusions: The study explores the relationship between CIPN and ADL affected during treatment for breast cancer. Through the motor and sensory symptoms reported by CIPNAT, nursing will have grant to develop educational strategies to prevent and minimize negative impacts on the quality of life of women with breast cancer undergoing treatment with neurotoxic agents.
Time from relapse after allogeneic stem cell transplantation (SCT) to donor leukocyte infusion (DLI) is longer, incidence of GVHD is higher, but survival is similar for recipients of unrelated DLI compared to matched sibling DLI.
Authors: A. Kumar, N. V. Frey, P. Vassilev, S. Goldstein, E. O. Hexner, A. W. Loren, R. Reshef, S. M. Luger, D. L. Porter, E. A. Stadtmauer
Journal: Journal of Clinical Oncology (2011)

6586 Background: DLI is potentially curative for patients who relapse after allogeneic SCT. Despite limited data comparing outcomes after unrelated DLI (uDLI) to matched sibling DLI (msDLI) there is an assumption that uDLI may be inferior because of 1) delay in administration due to logistical challenges and 2) increase in GVHD. Methods: We retrospectively reviewed records of 70 patients who received either msDLI or uDLI for relapse after SCT at our institution between 1/1/00 and 1/1/10. 44 patients received msDLI and 26 received uDLI. Indications for DLI were relapsed AML (31), MDS (13), ALL (6), CLL, HD, NHL (17), and MM (3). Distributions of disease were similar between all groups. At time of DLI no patient had active GVHD and all were off immunosuppression. 80% of acute leukemia patients received chemotherapy at a median of 11 days before DLI. Both groups received comparable cell doses. Results: Median time from relapse to msDLI was 39 days (range 14-389). Median time from relapse to uDLI was 62 days (20-181, p=.005). In acute leukemia patients, time from relapse to DLI was similar in both groups; 40.5 days (15-80) for msDLI and 59.5 days (23-99) for uDLI (p=0.14). Of note, time between request for uDLI to the NMDP and administration was an average of 39 days (16-110). In the entire cohort 28% had Grade III/IV GVHD; (16% of msDLI and 50% of uDLI recipients; p=.004). 15/70 (21%) DLI recipients remain alive without disease: 11 of 44 (25%, median survival 126 days) msDLI recipients and 4/26 (15%, median survival 219 days) uDLI recipients are alive (p=.33). Conclusions: The significant delay between relapse to DLI noted for all patients may be due to time for immunosuppression withdrawal, administration of chemotherapy before DLI and other factors not assessed in this analysis. The delay from relapse to DLI is longer for uDLI recipients, which may be due to logistical challenges when engaging unrelated donors. Further analyses are needed in to see if this delay impacts overall response and survival. Efforts to speed acquisition of uDLI and minimize GVHD may improve overall outcomes for relapse after unrelated donor SCT.
Comparison of two different schemes of neoadjuvant platinum-based concurrent chemoradiotherapy: The experience in the University Hospital Arnau de Vilanova of lleida (Spain).
Authors: M. Taberner Bonastre, D. Marquez-Medina, V. Garcia-Reglero, M. Deu-Martin, J. Duran Alama, S. Gomez-Falguera, L. Romero
Journal: Journal of Clinical Oncology (2011)

e17527 Background: Neoadjuvant concurrent chemoradiotherapy (CTRT) is a promising therapeutic approach for locally advanced non-small cell lung cancer (NSCLL), but the optimal regimen of drugs for the combination is not well defined. Methods: We retrospectively analyzed 33 stage IIA (T>5cm)-IIIB NSCLL treated with CTRT to 50 Gy maximum. They received 4 cycles of (A) Carboplatin AUC 5 day 1 plus paclitaxel 125 mg/m2 day 1 every 21 days (N=8) or (B) Cisplatin 75 mg/m2 day 1 plus Vinorelbine 60-80 mg/m2 days 1 and 8 every 21 days (N= 25), and concurrent radiotherapy during third and fourth cycle to 50 Gy maximum. After a second evaluation, tumors and mediastinal lymph nodes were resected or radiated to complete 60 Gy. Results: Percentage of stage IIIa and IIIb tumors were 37.5% and 62.5% for the A group and 44% and 48% for B group, respectively. There were not significant differences in radiological responses (p= 0.3). Tumor stabilizations were 87.5% vs. 88% in A and B group, respectively, and bigger than 90% radiologic responses were 12.5% vs. 4%. The B regimen obtained a higher rate of operability (25% vs. 54%, p= 0.225), but there was not significant differences in pathological response between A and B group (p= 0.52) (complete or minimum residual disease were 57.2% vs. 50%, and partial responses were 42.8% vs. 50%, respectively). Grade 3-4 toxicity were 0% vs. 8% for A and B group (p= 0.57). Mean relapse free survival was 19.2 months in the A group vs. 39 months in the B group (p= 0.55). The 6 month RFS was 75% in the A group vs. 68% in the B group (p= 0.54). Mean overall survival was 25.31 month in the A group and 36.86 months in the B group (p= 0.64). The 6-months overall survival was 75% in the A group and 96% in the B group (p= 0.76). Major pathological response did not impact on SLR (p= 0.26) or OS. Operability impacts in SLE (p= 0.002) and OS (p= 0.016). Conclusions: Both A and B are feasible and active CTRT regimens for the treatment of locally advanced NSCLC.
Identification of novel mutations of EGFR genome in lung adenocarcinoma.
Authors: Hsuan-Yu Chen, Gee-Chen Chang
Journal: Journal of Clinical Oncology (2014)

e22040 Background: Lung cancer has the highest cancer-caused death rate worldwide as well as in Taiwan. The epidermal growth factor receptor (EGFR) inhibitor related therapy demonstrated a good response in patients with EGFR mutation including L858R mutation or exon 19 deletion. However, the drug resistance (acquired resistant mutant T790M or alternative pathways) may develop after treating with EGFR-Tyrosine kinase inhibitor (TKI). Some wild-type patients may respond to TKI and some patients with L858R mutation or exon 19 deletion may still non-responsive to TKI target therapy. Methods: To explore additional sites of EGFR mutation or genomic variation with high correlation of EGFR TKIs response, we set an initial target of obtaining 130 patients with EGFR mutation status. The whole exons of EGFR genomic DNA will be captured and re-sequencing by next generation sequencer. Results: Total 130 lung adenocarcinomas were collected and cancer tissues were sequenced. Number of EGFR activating mutations were 27, 29, and 74 for L858R, exon 19 deletions, and wild type, respectively. The average depth was 128X and coverage 99.1% of EGFR genome. In addition, average number of synonymous SNV, nonsynonymous SNV, and InDels were 3.3, 1.2, and 2.0, respectively. A nonsynonymous SNV was obtained in many cancer tissues (105 out of 130, 80%). Total 10 nonsynonymous SNVs were not reported before and can be said as novel mutations. These novel mutations only obtained in few cancer tissues and the biological functions were still unknown. Conclusions: Although only lower frequency mutation will be found of cancer genome at this time. It is still worthy to develop new drug target after its biological functions are validated. We expect to obtain useful results for shedding lights on the additional sites of EGFR mutation or genomic variation and for helping the development of a molecular guidance of in the EGFR TKIs treatment.
A novel simplified approach to incorporating lymph node ratio into gastric cancer staging.
Authors: Sarah B. Fisher, Malcolm Hart Squires, Sameer H. Patel, David A. Kooby, Kenneth Cardona, Maria C. Russell, Charles A. Staley, Shishir K. Maithel
Journal: Journal of Clinical Oncology (2013)

24 Background: Previous investigators have reported on the value of lymph node ratio (LNR, defined as the number of positive nodes divided by the total number of nodes assessed) in gastric adenocarcinoma (GAC) staging. Given the complexity of previously proposed staging systems, it has not gained widespread acceptance. The aim of our study was to offer a novel simplified approach to incorporating LNR into gastric cancer staging. Methods: 131 patients who underwent curative intent resection with lymphadenectomy for GAC between 1/00-6/11 were identified. Clinicopathologic factors were assessed. Primary outcome was overall survival (OS). Results: Median age was 64 yrs, 51% were male. Median tumor size was 3.5 cm, 67% were poorly differentiated, 20% had perineural invasion, 31% had lymphovascular invasion, and 6% had a positive margin. Locoregional nodal metastases were present in 59% (n=77, N0: 41%, N1: 18%, N2: 22%, N3a: 14%, N3b: 5%). Median number of lymph nodes (LN) assessed was 15.5. Mean FU was 27.3 mos, median OS was 29.3 mos. Median LNR was 0.4 (.04-1). Patients with LNR ≥0.4 had decreased OS as compared to patients with LNR &lt;0.4 (15.1 vs 41.5 mos, p&lt;0.0001); the survival of patients with LNR &lt;0.4 was similar to that of node negative pts (48 mos, p=0.882). On Cox regression analysis, LNR ≥0.4 was more strongly associated with decreased OS (HR 3.09, 95%CI: 1.81-5.26; p&lt;0.0001) compared to the AJCC 7 th edition N stage (HR 1.36, 95%CI: 1.11-1.68; p=0.004). In the subset of patients who were inadequately staged and had &lt;16 nodes examined, a LNR ≥0.4 was associated with reduced survival compared to a LNR &lt;0.4 (17.3 vs 41.5 mos, p=.04). Conclusions: Compared to the current lymph node staging system, a lymph node ratio using 0.4 as the cutoff may more accurately predict survival outcomes. It seems to be particularly useful in patients who have inadequate nodal assessment. This simplified approach to lymph node ratio may be a more valuable staging tool than the current AJCC nodal staging system for gastric cancer and needs to be validated.
Limited-stage small cell lung cancer treated with concurrent irinotecan-platinum and radiation therapy.
Authors: M. E. Picton, T. Parent, S. Eubanks, Z. Nelson, P. R. Walker
Journal: Journal of Clinical Oncology (2011)

e17521 Background: Concurrent chemoradiation therapy (CRT) is a curative option for limited-stage small cell lung cancer (SCLC). The standard of care in the United States is concurrent etoposide-platinum CRT. However, in Asia CRT with irinotecan and cisplatin has been shown to be an effective and tolerable regimen. (Han et al. J Clin Oncol 2005; 23:3488 and Jeong et al. Lung Cancer 2006; 53:361) Irinotecan is a potent radiosensitizing agent (Tamura et al Jpn J Cancer Res 1997; 88:218). Patients with limited-stage SCLC treated with irinotecan-platinum concurrent CRT were identified from our institutional multidisciplinary thoracic oncology clinic database. Methods: Between May 2006 and December 2010, 26 patients with limited-stage SCLC were identified. 16 males; 10 females. Median age 64 years; 8 patients older than 70. Concurrent CRT with 65 mg/m2 irinotecan and 30 mg/m2 cisplatin day 1 and 8 every 21 days for 4 cycles; 4 patients received carboplatin in substitution for cisplatin. Thoracic radiotherapy started with cycle 2; 14 patients received 150 cGy twice-daily radiation in 30 fractions (45 Gy) and 11 patients received once daily radiation in 30 fractions (54 Gy). Seventeen patients underwent prophylactic cranial irradiation. Results: Objective response rate 88% (15 CR; 8 PR). 13/26 patients are alive at a median follow-up of 24 months. Median overall survival 13 months. The 1-year overall survival is 58%; 2-year overall survival is 33%. There were two cases of febrile neutropenia. Grade 3 esophagitis was observed in 2 patients. Two patients developed pneumatosis coli. Only 1 patient with symptomatic pneumonitis. Conclusions: Irinotecan and platinum concurrent CRT is an effective and well tolerated definitive treatment approach for limited-stage SCLC.
Gemcitabine, Busulfan and Melphalan (GemBuMel) Is a New High-Dose Chemotherapy (HDC) Regimen with High Activity In Refractory Hodgkin's Lymphoma (HL) Patients Receiving An Autologous Stem-Cell Transplant (ASCT): A Contemporaneous Comparison with BEAM and Busulfan/Melphalan (BuMel)
Authors: Yago Nieto, Paolo Anderlini, Uday Popat, Ping Liu, Borje S Andersson, Elizabeth J. Shpall, Partow Kebriaei, Chitra Hosing, Amin M Alousi, Muzaffar H. Qazilbash, Stefan O. Ciurea, Simrit Parmar, Richard E. Champlin, Roy Jones
Journal: Blood (2010)
Subset of patients with unfavorable T1N2-3M0 gastric cancer for whom surgery alone is the standard treatment.
Authors: Yukio Maezawa, Tsutomu Sato, Toru Aoyama, Kazuki Kano, Kenki Segami, Tetsushi Nakajima, Kousuke Ikeda, Tsutomu Hayashi, Takanobu Yamada, Chikara Kunisaki, Takashi Oshima, Yasushi Rino, Munetaka Masuda, Takashi Ogata, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2016)

105 Background: ACTS-GC trial demonstrated that S-1 is effective as adjuvant chemotherapy for Japanese patients who have undergone curative D2 gastrectomy for gastric cancer and were diagnosed with pathological stage II disease. However, stages T1N2M0 and T1N3M0, which are classified as part of Stage II, were excluded from the ACTS-GC trial. The aim of the present study was to identify the unfavorable subset of patients with T1N2M0 and T1N3M0 gastric cancer for whom surgery alone is the standard treatment. Methods: The present study examined 59 patients who were diagnosed with T1N2M0 or T1N3M0 gastric cancer at Kanagawa Cancer Center and Yokohama City University Hospital between January 2000 and June 2010. Univariate and multivariate analyses were performed to identify risk factors for overall survival using a Cox proportional hazards model. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter. A macroscopic tumor diameter greater than 30mm was regarded as a critical point of classification considering the survival. Mulitivariate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 60.0% in patients with a macroscopic tumor diameter &lt; 30mm, and 84.6% in those with a macroscopic tumor diameter &gt; 30mm (P = 0.027). Conclusions: Among T1N2M0 and T1N3M0 gastric cancer patients for whom surgery alone is the standard treatment, having a small T1N2-3 tumor of less than 30 mm in diameter was the sole risk factor for gastric cancer survival. These tumors might be another target for adjuvant chemotherapy.
Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.
Authors: Romain Mathieu, Juan David Ospina Arango, Veronique Beckendorf, Jean Bernard Delobel, Taha Messai, Alberto Bossi, Elisabeth Le Prise, Stephane Guerif, Jean-Marc Simon, Bernard M. Dubray, Jian Zhu, Jean-Leon Lagrange, Pascal Pommier, Khemara Gnep, Oscar Acosta, Renaud de Crevoisier
Journal: Journal of Clinical Oncology (2013)

53 Background: Tools are needed to predict toxicity after prostate cancer treatment. The objective of the study was to analyze late urinary toxicity after prostate cancer radiotherapy (RT) by symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. Methods: 965 patient received a median total dose of 70 Gy (range, 65-80 Gy) for localized prostate cancer, using different fractionations (2 or 2.5 Gy/day) and RT techniques. Medical history was recorded. Late urinary toxicity was assessed, prospectively in half of the patients, using the CTCAE v3 classification: urinary frequency, incontinence, bleeding and retention (dysuria). Patients or treatment related predictors of late urinary toxicity (&gt; grade 2) were identified by Univariate and multivariate Cox regression models. Nomograms were built up and their performance were assessed. Results: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, urinary retention and urinary incontinence rates were: 15%, 10%, 5%, 3% and 1%, respectively. The 5-year (≥ grade 3) urinary toxicity rate was 3%. The following parameters significantly increased the 5 year risk of global urinary toxicity (≥ grade 2): anticoagulant treatment (RR=2.35), total dose (RR=1.09), age (RR=1.06), bladder D25 (RR=1.03) and maximum dose (RR=1.1). Urinary frequency was increased by the total dose (RR=1.07) and diabetes (RR=4). Hematuria was increased by anticoagulant treatment (RR=2.9). Urinary retention (dysuria) was increased by the total dose (RR=1.1). Corresponding nomograms and their calibration plots were generated. Conclusions: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.
Comparison of pemetrexed plus cisplatin with other first-line doublets in advanced non-small cell lung cancer (NSCLC): A combined analysis of three phase III trials.
Authors: J. Treat, G. Scagliotti, G. Peng, M. J. Monberg, C. K. Obasaju
Journal: Journal of Clinical Oncology (2011)

e18004 Background: In a first-line study of advanced NSCLC, pemetrexed plus cisplatin (PC) was more effective among patients (pts) with nonsquamous histology compared with gemcitabine-cisplatin (GC, OS=11.8 vs 10.4 m, p=.005) while survival with PC was shorter than with GC in pts with squamous cell carcinoma. The comparability of PC to other commonly used regimens within histology subgroups needs to be explored. Methods: This retrospective analysis combined the pt-level data from 3,467 pts enrolled in one of three similar phase III trials (N=607, 1,725, and 1,135) with mature survival data comparing the efficacy of first-line doublets (6 cycles) in advanced NSCLC. Cox covariate-adjusted treatment hazard ratios (HRs) with 95% CI were obtained for OS. Overall and histology subgroup analyses were reported without adjustment for multiplicity. Results: In the overall analysis, adjusted HRs favored PC (HR <1.0) to each of the other 5 regimens. Among pts with nonsquamous histology, PC produced favorable HRs to each of the other regimens, achieving statistical significance when compared with vinorelbine-cisplatin and GC. Among pts with squamous histology, 4 of the 5 comparison regimens were favored to PC (HR >1.0), with only the comparison to GC achieving statistical significance. Conclusions: In the absence of randomized trial data comparing PC to commonly used doublets in advanced NSCLC other than GC, this analysis provides estimates for such comparisons. HR (95% CI) for contrast with pemetrexed-cisplatin Comparitors Overall Nonsquamous subgroup Squamous subgroup Gemcitabine-carboplatin 0.88 (0.65, 1.18) 0.80 (0.57, 1.14) 0.96 (0.53, 1.73) Gemcitabine-cisplatin 0.94 (0.84, 1.05) 0.85 (0.75, 0.97) 1.23 (1.01, 1.51) Gemcitabine-paclitaxel 0.91 (0.68, 1.22) 0.79 (0.56, 1.02) 1.26 (0.70, 2.27) Paclitaxel-carboplatin 0.91 (0.71, 1.17) 0.78 (0.58, 1.05) 1.34 (0.84, 2.11) Vinorelbine-cisplatin 0.80 (0.62, 1.03) 0.67 (0.50, 0.91) 1.25 (0.78, 2.02)
Final results of phase Ib of anticancer stem cell antibody tarextumab (OMP-59R5, TRXT, anti-Notch 2/3) in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC).
Authors: Eileen Mary O'Reilly, Lon S. Smith, Johanna C. Bendell, John H. Strickler, Mark Zalupski, William Gluck, Ann Kapoun, Wan-Ching Yen, Lu Xu, Dawn Hill, Lei Zhou, Jakob Dupont, Allen Lee Cohn
Journal: Journal of Clinical Oncology (2015)

278 Background: Tarextumab (TRXT), fully human IgG2 antibody, inhibits signaling Notch 2, 3 receptors. Tumor regression seen in Notch 3 patient-derived PC xenografts when TRXT added to Nab-P+Gem. The maximum tolerated dose (MTD) of single agent TRXT was 7.5mg/kg every other week (Smith, EORTC 2012); the main dose limiting toxicity (DLT) was Grade 3 diarrhea. This study evaluates MTD, pharmacokinetics (PK), pharmacodynamics (PD) and early efficacy of TRXT + Nab-P+Gem in mPC. Methods: Cohorts of 3-6 pts treated at 6 dose levels of TRXT. TRXT IV Days 1 + 15 with GEM 1000mg/m 2 alone (first two cohorts) or nab-P 125 mg/m 2 and GEM 1000mg/m 2 on Days 1, 8, 15 of every 28-day cycle. Biomarker analysis of surrogate tissue and tumor undertaken. Results: By 08/22/14, N= 40 treated. TRXT 15 mg/kg selected as Phase 2 dose. 1 DLT Grade 3 diarrhea in 15 mg/kg cohort. Frequently reported (≥15%) TRXT adverse events(AEs) were: diarrhea(60%), fatigue(43%), anemia(28%), decreased appetite (18%) and nausea(15%); most grade 1 or 2 and managed supportively. Other AEs (≥ 30%) were: cytopenia, alopecia, vomitng and peripheral edema. GEM or Nab-P+Gem did not alter PK of TRXT. Notch pathway-related genes, HEYL, HES2, NOTCH2 and cancer stem cell markers were altered in hair follicles at TRXT &gt; 7.5 mg/kg combined with Nab-P+Gem. Plasma, blood RNA biomarkers were also modulated by TRXT + Nab-P+Gem. Conclusions: TRXT + Nab-P+ Gem is well tolerated. 15 mg/kg is the selected Phase 2 dose of TRXT. Encouraging anti-tumor activity was observed. Final safety, efficacy, PK and PD results in surrogate and serial tumor tissues will be presented. The Phase 2 randomized, placebo-controlled ALPINE study is underway. Clinical trial information: NCT01647828. [Table: see text]