tbuckley/cabot-search huggingface dataset:
Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer.
Authors: S. Bayraktar, A. M. Gonzalez-Angulo, X. Lei, A. Buzdar, V. Valero, A. Melhem, H. M. Kuerer, G. N. Hortobagyi, A. A. Sahin, F. Meric-Bernstam
Journal: Journal of Clinical Oncology (2011)

532 Background: To evaluate the pathologic complete response (pCR) rates and relapse-free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline- or a nonanthracycline-based regimen. Methods: We reviewed records of 300 patients with HER2-positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH-FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival. Results: pCR rates were 60.6% and 43.3% for patients who received PH-FECH (n=235) and TCH (n=65), respectively (p=0.016). Patients who received PH-FECH were 1.45 times more likely to have a pCR (Odds ratio [OR]:1.45; 95% confidence interval (CI):1.06-1.98; P=0.02). At a median follow-up of 26.8 months for survivors, there were 28 recurrences and 15 deaths. Three-year RFS rates were 93% and 71% (P<0.001), and 3-year OS rates were 96% and 86% (p=0.008) for patients who received PH-FECH and TCH, respectively. Patients who received PH-FECH had a lower risk of recurrence (hazard ratio [HR]:0.27; 95% CI:0.12-0.60; p=0.001) and death (HR:0.37; 95% CI:0.12-1.13; p=0.08) than those treated with TCH. Conclusions: The type of NST in HER2-positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. While TCH is active, trastuzumab combined with a taxane and then with an anthracycline (PH-FECH) shows a higher pCR rate and a RFS advantage.
Quality of life (QOL) in patients with esophageal cancer treated with radiation (RT) in the radical setting.
Authors: Anita Choudhary, Geoffrey Liu, Pravin Philip Chacko, Ehab Fadhel, Charles Cho, Rachel Woo, Agnes Cheung, Catherine Vanderwater, Cindy Xin, Wei Xu, Jason Wong, Alex Lee, Zahra Kassam
Journal: Journal of Clinical Oncology (2015)

186 Background: QOL is poorly documented in patients with esophageal carcinoma treated with curative intent, especially trimodality therapy. QOL and survival outcomes were evaluated in a single centre prospective cohort study of esophageal carcinoma patients treated with RT in the radical setting. Methods: Patients completed the EORTC-QLQC30 at baseline, the end of RT, 6 months and 1 year after RT. A 10-point difference in scores was considered clinically significant. Results: Thirty-three of 45 consequently treated patients between February 2012 and June 2014 participated, all male, median age 63 years (range 40-76), with T1-4N1-3M0 disease (AJCC 7 th edn), median follow up 0.9 years (range 0.1-2.3). Four patients were treated definitively with chemoradiation 45-50Gy in 25 fractions; 14 neoadjuvantly 45-50Gy in 25 fractions; 15 neoadjuvantly 41.4Gy in 23 fractions, with concurrent chemotherapy. Compliance for questionnaire completion was 80-100%. 2 year overall survival (OS) and disease free survival (DFS) were 77% and 63%. Median scores on role, social, fatigue and appetite showed clinically significant worsening at the end of RT; in addition statistical significance was found for global QOL, physical, nausea/vomiting, and shortness of breath [median difference (MD): global -8.3 p=0.004, physical -6.6 p=0.003, role -16.6 p=0.001, social -16.6 p=0.78, nausea/vomiting 8.3 p=0.02, fatigue 22.2 p=0.001, shortness of breath 0 p=0.037, appetite 33.3 p=0.009]. At 6 months post RT global QOL (MD -16.6 p=0.23), physical (MD -13.3 p=0.007), role (MD -16.7 p=0.11) and fatigue (MD 11.1 p=0.18) were clinically significantly depressed. At one year all scores had returned to baseline, except pain, which was clinically significantly worse (MD 16.7 p=0.41); 64% of the cohort reported worse pain compared to baseline. Although global QOL on average returned to normal, 46% reported this to be clinically worse at one year compared to baseline. No association was found between baseline global QOL and OS (p=0.15) or DFS (p=0.57). Conclusions: QOL was worsened in several domains during and up to 6 months post RT. At one year all scores had returned to baseline except for pain which was significantly worsened in 64% of patients.
Breast cancer method of detection, stage at diagnosis, and delay in treatment in La Libertad province, Peru.
Authors: Anya Romanoff, Manuel Cedano Guadiamos, Tara Hayes Constant, Ana Maria Burga Vega, Joseph Zunt, Kay Johnson
Journal: Journal of Clinical Oncology (2015)

15 Background: The majority of breast cancer deaths occur in low- and middle-income countries, as a result of late stage disease presentation and inadequate access to diagnosis and treatment. Delay from development of symptomatology to initiation of treatment is associated with more advanced breast cancer, and delays greater than three months have been associated with reduced survival. We investigated method of detection, disease stage, and time to diagnosis and treatment in breast cancer patients in Peru. Methods: This investigation was conducted at the Instituto Regional de Enfermedades Neoplasicas del Norte, in Trujillo, Peru. All women with a pathologic or clinical diagnosis of breast cancer who visited a breast surgeon from February-May 2015 were eligible to participate. Trained personnel conducted individual patient interviews in Spanish, utilizing a validated breast cancer delays questionnaire. Results: Of the 159 women who qualified for inclusion, 113 (71%) agreed to participate in the study. Mean age was 54 years (range 30-85). Patients lived an average of 3 hours from the oncology institute (range 0-36). Most households earned less than minimum wage, and most (66%) were covered by Seguro Integral de Salud, the government-funded medical insurance for citizens with limited financial resources. One hundred and five (93%) participants reported initially detecting their breast cancer as a result of symptoms. One cancer (1%) was detected during screening clinical breast examination, and 7 (6%) by screening mammography. Ninety-three patients had available stage at time of diagnosis, with the following distribution: stage 0- 2%, stage 1-3%, stage 2-44%, stage 3-48%, and stage 4-3%. Based on patient report, mean patient delay (symptom development to first medical visit at any facility) was 211 days. Mean provider delay (first medical visit until treatment initiation) was 241 days. Mean total delay (symptom development to treatment initiation) was 407 days. Conclusions: Almost all study participants initially detected their breast cancer as a result of symptoms. More than half presented with stage 3 or 4 disease. Average delay from symptom onset to start of treatment was greater than one year.
Comparative effectiveness of combination TACE/ablation vs. monotherapy in hepatocellular carcinoma.
Authors: Arthur Winer, Yohei Rosen, Frederick Lu, Russell S. Berman, Marcovalerio Melis, George Miller, H. Leon Pachter, Elliot Newman, Ioannis Hatzaras
Journal: Journal of Clinical Oncology (2016)

350 Background: Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death worldwide. Loco-regional treatment modalities for HCC include Trans-Arterial Chemoembolization (TACE) and Radiofrequency/Microwave Ablation (RFA/MWA). Studies have shown that dual therapy with both TACE and ablation is beneficial, though data is limited. We retrospectively studied all HCC patients treated with either TACE, ablation, or dual therapy at a tertiary referral public hospital to determine differences in survival. Methods: Following IRB approval, all patients diagnosed with HCC (1998-2013) at our institution were retrospectively analyzed for date of diagnosis, treatment-type, length of follow-up, and survival. Patients were excluded if they did not undergo TACE or RFA/MWA, or underwent other treatments, such as surgery. The primary outcome was all-cause mortality 5 years after diagnosis. Kaplan Meier curves were created and statistics with Log-rank testing and hazard ratios (HR) were performed. Results: Of 509 patients diagnosed with HCC, 109 (21.4%) met inclusion criteria. 60 were treated with TACE alone, 30 with ablation alone, and 19 were treated with both, either concomitantly or in sequence. Median follow-up and overall median survival was 15.5, 19, and 52 months for TACE, ablation, and dual therapy, respectively. Survival at 5 years was 11.9%, 13.3% and 42.1% for TACE, ablation, and combination groups respectively. Kaplan Meier analysis revealed a significant increase in survival in the combination therapy group vs. RFA or TACE alone at 5 years (p = 0.0006). However, there was no significant difference in survival when comparing TACE vs. RFA/MWA at 5 years (HR = 1.18, p = 0.48). Conclusions: Our study suggests a greater survival benefit for patients treated with TACE and RFA/MWA versus either modality alone.
Phase II Study of Short Course CHOP-Rituximab Followed by 90-Y Ibritumomab Tiuxetan as First-Line Treatment for Follicular Lymphoma: An Update and Extension of Preliminary Findings on Predictors of Relapse.
Authors: Rachel C. Jankowitz, Kenneth A. Foon, The Minh Luong, Stephanie R. Land, Nicholas A. DeMonaco, Steven H. Swerdlow, Judith Joyce, Jennifer Osborn, Terry Evans, Samuel A. Jacobs
Journal: Blood (2008)
Cord Blood Transplantation from Unrelated Donor for Treatment of Childhood Acute Myeloid Leukemia: A Japan Cord Blood Bank Network Analysis.
Authors: Keiichi Isoyama, Koji Kato, Minoko Takanashi, Hiroshi Azuma, Tokiko Nagamura-Inoue, Shunro Kai, Megumu Oda, Masao Nakabayashi, Shunichi Kato
Journal: Blood (2006)
Tumor infiltration by chemokine receptor 7 (CCR-7)–expressing T lymphocytes to predict outcome in advanced colorectal carcinoma patients.
Authors: P. Correale, M. S. Rotundo, M. T. Del vecchio, C. Botta, S. Apollinari, D. Ciliberto, E. Bestoso, P. Tassone, P. Tagliaferri
Journal: Journal of Clinical Oncology (2011)

e14056 Background: An efficient anti-tumor immune-response is considered a critical factor for a good outcome and a prolonged survival in colorectal cancer patients. The extent of tumor infiltration by different T-lymphocyte subsets, which represents patients’ state of immune-competence, may reflect a completely different outcome. We have evaluated in advanced colorectal cancer patients the prognostic role of tumor infiltration by cytotoxic (CD8+) T cells expressing the chemokine receptor 7 (CCR7). We also investigated if the presence of this lymphocyte subset might correlate with tumor infiltration by regulatory (Treg) T cells. Methods: The infiltration of CD3+, CD8+, CD4+, CD8+CCR-7+ (Tccr7) and CD4+FoxP3+- (Treg) -T lymphocytes was investigated by immunohistochemistry in the tumor samples at diagnosis of 76 advanced colorectal cancer patients. We searched for a possible correlation of Tccr7 tumor infiltration score with either Treg tumor infiltration extent and patient outcome. Results: High Tccr7 tumor infiltration score was highly predictive of a prolonged overall survival (OS) [high v.s. low score: 41.3 months (95%CI: 30.7-51.9) v.s. 26 (95% CI: 20.6-33.2) months, hazard ratio (HR) = 0.52 (95 %CI: 0.27-0.99); P=0.048)] with a trend to a better treatment related survival and time to progression to first-line chemotherapy. No correlation by regression curve analysis could be demonstrated between Tccr7 and Treg tumor infiltration scores; however, a cluster of patients with a concomitant high infiltration by both T cell populations was identified, who presented a very positive outcome [double high v.s. double low tumor infiltration score: OS= 44 months (95%CI: 27.5-60.4) v.s. 26.1 (95%CI:18.3-34); HR= 0.41 (95%CI: 0.20- 0.93); P=0.03). Conclusions: High Tccr7 tumor infiltration at diagnosis represents a favorable prognostic factor for advanced colorectal cancer patients. A critical role of local immune-response for the long term survival of colorectal cancer patients is suggested.
Development and validation of contouring guidelines for post-cystectomy adjuvant radiation of bladder cancer.
Authors: Brian C. Baumann, Walter Bosch, Amit Bahl, Alison J. Birtle, Rodney H. Breau, Amarnath Challapalli, Albert Chang, Ananya Choudhury, Siamak Daneshmand, Adam S. Feldman, Thomas J. Guzzo, Serena Hilman, Ashesh B. Jani, S. Bruce Malkowicz, Viraj A. Master, Anita Mitra, Sima P. Porten, Jason A. Efstathiou, Libni Eapen, John Paul Christodouleas
Journal: Journal of Clinical Oncology (2016)

409 Background: Several organizations are developing clinical trials to evaluate adjuvant radiotherapy (RT) for bladder cancer patients at elevated risk of locoregional failure (LF). However, the clinical target volumes (CTVs) &amp; organs at risk (OARs) for this treatment have not been defined in detail. Our purpose was to define multi-institutional consensus CTVs &amp; OARs for male &amp; female bladder cancer patients undergoing adjuvant RT in clinical trials. Methods: We convened a multi-disciplinary group of bladder cancer specialists from 9 centers in 3 countries. 5 radiation oncologists (ROs) &amp; 7 urologists participated in the development of the proposed contours. The group proposed initial language for the CTVs &amp; OARs and contoured them on CT scans of a male &amp; female cystectomy patient with input from ≥ 1 urologist at each center. Using the binomial maximum-likelihood estimates method, we generated 95% level initial contours. We evaluated the contours for level of agreement using the Landis &amp; Koch interpretation of the K statistic. Based on the initial contouring, the group updated its descriptions of the CTVs &amp; OARs. To determine if the revised language produced consistent contours, the cystectomy bed (CB) contour was redrawn on the CT sets by an additional 5 ROs. Results: The group proposed that patients at elevated risk for LF with R0 resections should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac &amp; presacral) whereas patients with ≥ R1 resections should be treated to the pelvic nodes &amp; CB. The group proposed the rectum, bowel space, bone marrow &amp; urinary diversion as OARs. The level of agreement for the initial CTVs &amp; OARs from the group varied substantially (Table). Consensus language to describe CTV &amp; OAR structures where the initial contours varied was successfully developed. Contours &amp; feedback from the validation group are being analyzed. Conclusions: Initial descriptions of CTVs &amp; OARs have been successfully developed. External validation &amp; feedback are pending. The results will be applicable to clinical trials of adjuvant RT in bladder cancer. [Table: see text]
Association of diastolic blood pressure (dBP) ≥ 90 mmHg with overall survival (OS) in patients treated with axitinib (AG- 013736)
Authors: B. I. Rini, J. H. Schiller, J. P. Fruehauf, E. E. Cohen, J. C. Tarazi, B. Rosbrook, A. D. Ricart, A. J. Olszanski, S. Kim, J. Spano
Journal: Journal of Clinical Oncology (2008)

3543 Background: Axitinib is an oral, potent and selective inhibitor of VEGF receptors 1, 2 and 3 in clinical development in multiple tumor types. BP elevation has been proposed as a potential efficacy marker of VEGF receptor inhibitors. The relationship between dBP ≥ 90 mmHg and OS was explored retrospectively across 6 separate phase II axitinib studies. Methods: Pts with non-small cell lung cancer (NSCLC), cytokine-refractory renal cell cancer (RCC), sorafenib-refractory RCC, thyroid cancer or melanoma received 5 mg BID single- agent axitinib; advanced pancreatic cancer (APC) pts received gemcitabine (GEM) 1000 mg/m2 on days 1, 8, and 15 in 28-day cycles plus 5 mg BID axitinib. All 6 studies required BP ≤140/90 mmHg at baseline. BP was measured in clinic at every visit (days 1, 8, and 15 for APC, every 2 weeks for sorafenib-refractory RCC and every 4 weeks for all other studies) and daily at home by patients. Only in-clinic BP measurements were used in this analysis. Antihypertensive medications and/or axitinib dose modifications were used to manage BP as pre-specified in each protocol. OS was estimated using Kaplan-Meier method. Results: A total of 307 pts received axitinib across 6 phase II studies: 32 pts with NSCLC, 52 pts with cytokine-refractory RCC, 62 pts with sorafenib-refractory RCC, 60 pts with thyroid cancer, 32 pts with melanoma and 69 pts with APC. Hypertension as an adverse event was reported in 120 pts (39.2% all grades); grade 3 in 32 pts (10.5%) and grade 4 in 2 pts (0.7%). Median OS (mOS) of pts without any dBP ≥90 mmHg during treatment vs. those with at least 1 dBP ≥90 mmHg are shown in Table below. Conclusions: In this retrospective analysis across multiple tumor types, the occurrence of dBP ≥90 mmHg appears to be associated with longer OS. Blood pressure as a potential efficacy marker requires validation in future trials. mOS of pts without dBP ≥ 90 mmHg; months (n) mOS of pts with dBP ≥90 mmHg; months (n) APC (axitinib+GEM) 5.2 (31) 12.2 (38) Melanoma 6.4 (19) 13.0 (13) Sorafenib-refractory RCC 8.4 (23) Not reached (39) NSCLC 11.6 (19) 15.8 (13) Cytokine-refractory RCC 12.9 (20) Not reached (32) Thyroid cancer 21.6 (21) Not reached (39) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Pfizer Oncology Pfizer Oncology Pfizer Oncology Pfizer Oncology
KIF3A genetic variation is associated with pediatric asthma in the presence of eczema independent of allergic rhinitis
Authors: Elisabet Johansson, Jocelyn M. Biagini Myers, Lisa J. Martin, Hua He, Valentina Pilipenko, Tesfaye Mersha, Matthew Weirauch, Nathan Salomonis, Patrick Ryan, Grace K. LeMasters, David I. Bernstein, James Lockey, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2017)
Whole-exome tumor sequencing study in patients with biliary cancer with a response to MEK inhibitors.
Authors: Daniel H. Ahn, Hatice Gulcin Ozer, Baris Hancioglu, Gregory B. Lesinski, Cynthia Dawn Timmers, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2016)

253 Background: We conducted a phase-II study with selumetinib (AZD6244), a small molecule inhibitor of MEK1/2, in advanced biliary tract cancers (BTC). The observed preliminary activity was confirmed with another MEK inhibitor (MEK162) that was tested in a similar patient population. To assess for tumor-specific genetic variants that mediate sensitivity to MEK inhibition in BTC, we performed whole-exome sequencing in patients with an objective response including a complete response to selumetinib. Methods: Normal and tumor DNA from available formalin-fixed paraffin-embedded tissue from biopsies of primary or metastatic tumor from two patients who experienced an objective response underwent whole-exome sequencing. Raw sequence reads were processed with GATK workflow and tumor-specific variants were identified using MuTect and VarScan 2. Following, we assessed the functional consequences of the variants. Copy number changes and potential gene fusion events were also screened. We compared the findings to assess for any commonality between the two samples. Ingenuity Pathway Analysis was used to assess whether the identified somatic variants were intrinsic to the MAPK pathway. Results: 1169 and 628 tumor-specific variants were identified in the two tumor samples. Further analysis demonstrated a similar number of functional and novel variants between the two samples, which were 60 and 53, respectively. No common variants or detectable fusion events were observed between the two samples. Copy number changes were found in chromosomes 1, 5, 6, 9, 10, 12, 17, 20, 21 and 22 in sample one, and in chromosome 11 and 12 on sample two with no common findings. Several variants in genes associated with ERK signaling were present in each tumor sample. Conclusions: Although no common tumor-specific somatic changes of significance several genes associated with ERK signaling were identified in the patients with an objective response. Confirmatory studies investigating the role of the identified genes need to be further investigated.
Mitomycin-C induction and maintenance topical therapy for upper tract urothelial carcinoma
Authors: Gavin Neal Wagenheim, John Papadopolous, Neema Navai, John W. Davis, Jose A. Karam, Ashish M. Kamat, Christopher G. Wood, Colin P. N. Dinney, Surena F. Matin
Journal: Journal of Clinical Oncology (2016)

411 Background: Reported recurrence rates following endoscopic treatment of upper tract urothelial carcinoma (UTUC) are high, from 30% to 70%. Adjuvant BCG topical therapy results are inferior to what is seen in adjuvant treatment of bladder cancer. This is likely due to difficulty in definitive delivery to the upper tract and the absence of a reservoir for dwell times. There is limited reported use of adjuvant mitomycin-c (MMC) for UTUC, and to our knowledge no reported experience of topical delivery using the SWOG maintenance regimen. We hypothesized that a chemotherapeutic agent may be effective topical therapy of the upper tract, particularly when given using SWOG recommendations. We report efficacy, safety, and tolerability of this approach. Methods: We reviewed charts of patients undergoing primary endoscopic biopsy/resection and ablation of an UTUC, recording clinical, pathologic, laboratory, and follow up information. Patients were offered induction and maintenance topical therapy after endoscopic control. MMC was given as initial adjuvant topical agent for 6 weeks induction and 3 weeks maintenance for up to 2 years per SWOG protocol. Delivery was either via percutaneous nephrostomy or ureteral catheter, per patient preference. Results: 28 patients were identified, 21 (75%) low grade and 7 (25%) high grade. Delivery of MMC was via percutaneous nephrostomy in 29% and ureteral catheter in 71%. 46% were treated on an imperative basis, 46% elective, and 7% palliative. No patients discontinued therapy due to intolerance, and 61% received maintenance. Only 11% of patients undergoing induction and 6% maintenance incurred complications. With a mean follow up of 22 months (range 1−79), recurrence-free, progression-free, and nephroureterectomy-free survival in all patients, low-grade patients, and high-grade patients was 68%, 67%, and 71%; 89%, 90%, and 86%; and 89%, 90%, and 86%, respectively. Conclusions: In patients with complete endoscopic control, upper tract topical instillation of MMC induction and maintenance via percutaneous nephrostomy or ureteral catheter is a well−tolerated, feasible, and perhaps beneficial treatment of low-grade and possibly high-grade tumors.