tbuckley/cabot-search huggingface dataset:
Induction chemotherapy with cisplatin plus weekly paclitaxel followed by concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN): Single center experience in the south of Brazil.
Authors: Janaina Brollo, Sargeele Silva, Claudio Pescador, Catarine S Medeiros, Bruna C Silva, Bruno A Duso, Catherine Gotardo, Debora Weschenfelder, Diego Gnatta, Isnard E Litvin, Maximiliano C Kneubil, Alessandra EF Godoy, Rita De Cassia Costamilan, Sara Boscato, Ana Maria R Oliveira, Andre B. Reiriz
Journal: Journal of Clinical Oncology (2015)

e17009 Background: The paclitaxel/cisplatin is a non-infusional alternative for induction chemotherapy of LASCCHN based on phase II trials. Here, we describe our institutional experience with this combination in the South of Brazil. Methods: Twenty-nine consecutive patients with unresectable LASCCHN were accrued between April/2012 to June/2014. They received weekly paclitaxel at the dose of 80 mg/m2 plus cisplatin at the dose of 75 mg/m2 on day 1 for three cycles followed by chemoradiotherapy with cisplatin and standard dose. Overall response, toxicity, disease free survival (DFS) and overall survival (OS) were evaluated. Results: The median follow up was 13.3 months. The average age was 58.6 years and 96.5% had PS 0-1 (ECOG). Most of the patients had bulky stage IVa and IVb disease, 55.2% and 24.1% , respectively. Concerning primary site of tumor, 31% of patients had oropharingeal, 31% larynx and 27.6% oral cavity. The major part of patients had heavy smoking and alcohol history. Twenty-one patients (72.4%) completed the planned treatment and four patients (13.8%) underwent exclusive radiotherapy after induction chemotherapy. All patients were evaluated for response, with complete response and partial response documented in 75.9% and 20.7% of cases, respectively. All patients were evaluated for toxicity, with severe (grade 3-4) mucositis, asthenia, neutropenia, anemia and trombocytopenia being observed in 17.2%, 10.3%, 6.9%, 6.9% and 3.4%, respectively. One treatment-related death was documented (3.4%). The 1- and 2-year DFS rate were 81.5% and 64.8%, respectively; and the 1- and 2-year OS rate were 96.4% and 65.7%, respectively. Conclusions: Our results confirm previous observations that induction chemotherapy paclitaxel and cisplatin is a well-tolerated and highly active regimen for the treatment of patients with LASSHNC with low acute toxicity and excellent locorregional control and survival rate.
Effect of angiotensin converting enzyme inhibition on toxicity in patients undergoing radiation with or without chemotherapy for head and neck cancer.
Authors: Rebecca A. Redman, Callie Linden, Cesar Augusto Perez, Neal E Dunlap, Craig Silverman, Paul Tennant, Jeffrey Bumpous, Mary Gregg, Xiaoyong Wu, Shesh Rai
Journal: Journal of Clinical Oncology (2015)

e17098 Background: Inhibition of the renin-angiotensin system may be associated with improved outcomes in cancer patients. Angiotensin-converting enzyme inhibitors (ACE-I) may lessen radiation-induced pneumonitis in patients with lung cancer, and in vivo data suggest ACE-I may modulate radiation-induced brain injury. It is not yet known whether ACE-I mitigate radiation-induced toxicities in head and neck cancer patients. Methods: We report the results of a retrospective chart review of consecutive patients with HNSCC treated with radiation, with or without chemotherapy, at a single institution. Those with recurrent disease or who had received prior radiation were excluded. Charts were evaluated to determine whether or not a patient was incidentally on an ACE-I at the time of their cancer treatment. Results: A total of 98 patients met the criteria for inclusion with at least two years of followup. Demographics of the two cohorts (ACE-I or no ACE-I) were similar in terms of gender, race, smoking history, alcohol consumption, stage, disease site, radiation dose, and HPV status of the tumor. On average, the patients taking ACE-I were older (median age 61.5 years v. 56.5 years, p 0.053) and were less likely to have received chemotherapy (45.0% v. 69.2%, p 0.044). Incidence and grade of radiation dermatitis was similar between the cohorts (p 0.953). Grade 3 or higher any toxicity was also similar (50.0% v. 46.2%, p 0.758). Only 15.0% of patient taking ACE-I lost 10% of baseline weight compared to 43.6% of those not taking ACE-I (p 0.019). This was also reflected in a less frequent need for feeding tube placement (25.0% v. 53.8%, p 0.029). Conclusions: Angiotensin converting enzyme inhibition may decrease treatment-related weight loss and need for feeding tube placement in patients with head and neck cancer undergoing radiation, with or without chemotherapy.
A phase III randomized intergroup trial (S0016) comparing CHOP plus rituximab with CHOP plus iodine-131-tositumomab for front-line treatment of follicular lymphoma: Results of subset analyses and a comparison of prognostic models.
Authors: Oliver W. Press, Joseph M Unger, Michael Leo LeBlanc, Lisa M. Rimsza, Jonathan W. Friedberg, Myron Stefan Czuczman, Mark Stefan Kaminski, Rita M Braziel, Catherine M Spier, David G. Maloney, Bruce D. Cheson, Thomas P. Miller, Richard I. Fisher
Journal: Journal of Clinical Oncology (2012)

8001 Background: Advanced follicular lymphomas (FL) are considered incurable with chemotherapy and there is no consensus on the best treatment. Outcomes are variable, but can be partially predicted by defined prognostic factors. SWOG and CALGB compared the safety and efficacy of 2 immunochemotherapy regimens in a Phase III trial enrolling 554 patients between 3/1/2001 and 9/15/2008. Methods: Patients were eligible if they had bulky stage II, III or IV FL and had not received prior therapy. Patients randomized to CHOP-R received 6 cycles of CHOP every 21 days + 6 doses of rituximab. Patients randomized to CHOP-RIT received 6 cycles of CHOP, followed by consolidative radioimmunotherapy with tositumomab/iodine I-131 tositumomab. A Cox proportional hazards multi-variable regression analysis assessed the prognostic impact of age, stage, LDH, LN size and number, performance status, hemoglobin, β2 microglobulin, BM involvement, and B symptoms. The prognostic value of 3 multi-variable models were compared. Results: Outcomes were outstanding with either CHOP-R or CHOP-RIT (2 yr PFS: 76% vs 80% [ p =0.11]; 2 yr OS: 97% vs 93% [p =0.08], respectively). Subset analyses so far have not identified any subgroups clearly benefitting to a greater degree from CHOP-R or CHOP-RIT in terms of both PFS and OS. Cox multivariable regression analysis identified serum-β2M, LDH level, and FLIPI index as the strongest prognostic factors associated with worse PFS and OS. Conclusions: Both regimens produced outstanding PFS and OS, and no statistically significant differences between them were observed. FLIPI, FLIPI2, and LDH + β2M models were all strong predictors of patient outcomes. A combination of LDH + β2M was as good as the FLIPI index, and was simpler to apply. (Supported in part by NCI grants CA32102 and CA38926 from the NCI and GlaxoSmithKline.) [Table: see text]
CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells
Authors: Gwenola Manic, Michele Signore, Antonella Sistigu, Giorgio Russo, Francesca Corradi, Silvia Siteni, Martina Musella, Sara Vitale, Maria Laura De Angelis, Matteo Pallocca, Carla Azzurra Amoreo, Francesca Sperati, Simone Di Franco, Sabina Barresi, Eleonora Policicchio, Gabriele De Luca, Francesca De Nicola, Marcella Mottolese, Ann Zeuner, Maurizio Fanciulli, Giorgio Stassi, Marcello Maugeri-Saccà, Marta Baiocchi, Marco Tartaglia, Ilio Vitale, Ruggero De Maria
Journal: Gut (2017)

Objective Cancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies. Design To discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein microarray (RPPA) and cytogenetic analyses, and validated by immunostainings. DNA replication stress (RS) was increased by employing DNA replication-perturbing or polyploidising agents. Results The drug-library screening led to the identification of LY2606368 as a potent anti-CSC agent acting in vitro and in vivo in tumour cells from a considerable number of patients (∼36%). By inhibiting checkpoint kinase (CHK)1, LY2606368 affected DNA replication in most CRC-SCs, including RAS-mutated ones, forcing them into premature, lethal mitoses. Parallel genomic, RPPA and cytogenetic analyses indicated that CRC-SCs sensitive to LY2606368 displayed signs of ongoing RS response, including the phosphorylation of RPA32 and ataxia telangiectasia mutated serine/threonine kinase (ATM). This was associated with mutation(s) in TP53 and hyperdiploidy, and made these CRC-SCs exquisitely dependent on CHK1 function. Accordingly, experimental increase of RS sensitised resistant CRC-SCs to LY2606368. Conclusions LY2606368 selectively eliminates replication-stressed, p53-deficient and hyperdiploid CRC-SCs independently of RAS mutational status. These results provide a strong rationale for biomarker-driven clinical trials with LY2606368 in patients with CRC.
Bringing the patient voice into quality assessment: National stakeholder perceptions of facilitators and barriers for the use of PROs as performance measures.
Authors: Angela M. Stover, Arlene Chung, Jennifer Jansen, Ethan M. Basch
Journal: Journal of Clinical Oncology (2017)

61 Background: An emerging trend in quality improvement is to incorporate the patient voice into performance metrics for routine care delivery using patient-reported outcomes (PRO). For instance, patients may complete a questionnaire about how well their symptoms are controlled (e.g., nausea). High-quality care is then determined by adjusting scores and comparing similar practices on symptom control. However, stakeholder (clinicians, administrators, and researchers) perspectives of facilitators and barriers are not well characterized because PRO performance measures are an emerging concept. Methods: Key informant interviews were conducted with 35 stakeholders (9 medical oncology clinicians, 13 administrators, and 13 health services researchers) from 5 healthcare systems across the U.S. Interview guides were used to elicit perceptions of barriers, facilitators, and acceptability for using PROs as performance measures. Transcripts were content analyzed by stakeholder group using standard methodology. Results: Clinicians reported barriers that were structural (e.g., complexity of programming electronic health record [EHR] changes) and process-oriented (e.g., changing clinic workflow to accommodate PRO review and alerts). Clinicians noted concerns about appropriate adjustments to ensure fair quality comparisons across practices. Clinicians and administrators reported structural barriers such as reimbursement and staff training, and outcome barriers such as choosing symptoms that have clear treatment guidelines. Facilitators included dashboards to visually display results that are intuitive and easily accessible in the EHR. Researchers focused on standardization and selecting thresholds for symptom alerts. Conclusions: Clinicians, administrators, and researchers reported barriers to the integration of PROs as quality measures. These barriers are mainly structural- and process-oriented but generally did not focus on acceptability. Facilitators focused on presenting PRO scores in an easily interpretable and accessible way within the EHR. Results will inform multi-site feasibility testing of PROs as quality metrics.
Surprising activity of nilutamide in post-castration progressive prostate cancer
Authors: A. O. Sartor, D. Lifsey, A. C. Dwight
Journal: Journal of Clinical Oncology (2004)

4762 Background: Increasingly patients with post-castration prostate cancer seek treatment for PSA only progression. Many of these patients are elderly, have considerable co-morbidities, are concerned about a rising PSA, and seek relatively non-toxic therapies. Methods: Twelve patients with progressive post-castration prostate cancer were treated with oral nilutamide at FDA approved doses (150 mg/day). LHRH agonist maintenance therapy was continued in non-surgically castrated patients. Monthly PSA monitoring was recommended. PSA progression was defined as a 25% increase from baseline or nadir with a minimum increase of 5 ng/ml as recommended by Bubley et al (J Clin Oncol 17:3461). Results: All patients had failed either orchiectomy (n=2) or LHRH agonist therapy (n=10) and had clear evidence of a rising PSA prior to starting nilutamide. Median age was 81 (range 62–87), median PSA was 12 ng/ml (range 2.7–92.1), and radiographically positive metastatic disease was present in 33% (4/12). Antiandrogens were previously used in 50% of patients (5/12 were bicalutamide pretreated, 1/12 were pretreated with flutamide). PSA declines were noted in 9/12 patients; PSA declines of >50% were noted in 4/12 (33%) patients. Median progression free survival was 7 months (range 1–36+). One patient had CT evidence of progression without PSA progression. Progression-free survival of more than 6 months was noted in both antiandrogen (4/6) and non-antiandrogen (2/6) pretreated patients. One patient became nauseated after four doses and refused further therapy, two patients had fatigue and weight loss and stopped therapy prior to PSA progression. No other toxicities were noted except alterations in visual light-dark adaptation Conclusions: Nilutamide at FDA approved dosages can delay PSA progression in patients with prostate cancer failing to respond to primary androgen deprivation therapies. Toxicities necessitated cessation of therapy in 3/12 patients. No significant financial relationships to disclose.
Improving care coordination for brain tumor patients through value-based care redesign of a virtual integrated practice unit.
Authors: Phioanh Leia Nghiemphu, Darlene Dezelan, Jackie H Tran, Timothy Francis Cloughesy, Linda M. Liau, Christine Ahn, Preston White
Journal: Journal of Clinical Oncology (2017)

110 Background: Brain tumor care at our institution involves providers from multiple departments in separate clinics and can cause patient frustration and poor patient experience. We previously reported on engaging care teams from Neurosurgery, Neuro-Oncology, Radiation Oncology, Neuroradiology and Neuropathology using lean methodology to re-design the care pathway for patients with brain tumors. A Patient Navigator Program was also established to help with patient’s care coordination. For this study, we evaluate whether this value-based care redesign has improved patient coordination and satisfaction. Methods: The care pathway and navigator process were implemented at the end of Dec 2015. We identified 202 patients who had brain tumor resections and were followed by our Navigator Program from July 2015 – Sept 2016. We evaluated the time from surgery to appointments and whether these appointments were all made within 1 week. We also reviewed our patient satisfaction scores using Press Ganey percentile ranks and HCAHPS metrics in the areas of patient education and coordination. We compared these data from July-Dec 2015 (pre-redesign) to data from Jan-Sep 2016 (post-redesign). Results: Of the patients followed by the Navigator Program, 137 patients required follow-up with providers from at least 2 different departments for treatment planning. Pre-redesign, the program followed 49 patients and made their appointments 14 median days from surgery (range 3-37), with 59% within 1 week. The 88 patients followed after-redesign had appointments in 16 median days (range 1-33) with 70% scheduled within 1 week. Pre-redesign, our Press Ganey Percentile rank ranged from 1 st -32 nd . After-redesign, the ranks increased to 16th-99th percentile, with most domains over the 80th percentile. Patients also reported higher satisfaction on HCAHPS post-redesign compared to pre-redesign. Conclusions: Development of a clear process for care coordination within the patient navigator program helped improve our patient satisfaction and streamline timely follow-up care. For our future coordination, we will implement a centralized access to care for our patients with brain tumors.
Conditional Survival: An Assessment of the Prognosis of Patients at Time Points After Initial Diagnosis and Treatment of Locoregional Melanoma Metastasis
Authors: Lauren E. Haydu, Richard A. Scolyer, Serigne Lo, Michael J. Quinn, Robyn P.M. Saw, Kerwin F. Shannon, Andrew J. Spillane, Jonathan R. Stretch, William H. McCarthy, John F. Thompson
Journal: Journal of Clinical Oncology (2017)

Purpose Standard cancer staging and prognostic estimates are determined at the time of the patient's initial disease presentation. Conditional survival is an alternative, dynamic assessment from follow-up time points after the initial disease diagnosis and is based on the condition of survivorship. Estimates of conditional survival can provide critical prognostic information for patients and clinicians, guide subsequent cancer follow-up schedules, and influence decisions regarding treatments. The current study presents conditional survival estimates developed from a cohort of 4,540 patients diagnosed with stage III melanoma treated at a single institution. Methods Patients with stage III disease at first melanoma diagnosis (initial; n = 2,042), or who developed locoregional metastasis as a first recurrence some time after primary diagnosis (recurrent; n = 2,498), were assessed. Conditional melanoma-specific survival (MSS) estimates up to 5 years after diagnosis were adjusted for age, sex, and 8th edition American Joint Committee on Cancer (AJCC) stage. Results Older age at diagnosis of stage III disease conveyed a worse prognosis at each conditional survival time point. Males had significantly worse MSS outcomes for up to 2 years of conditional survival, after which males and females had similar MSS. For patients with AJCC stage IIIB and stage IIIC disease, MSS outcomes were similar to those of patients with stage IIIA disease after 3 and 5 years of survivorship, respectively. Conclusion Adjuvant systemic treatments may have the greatest benefit when administered within the first 2 years of stage III melanoma diagnosis, during which period prognosis is significantly worse for male patients of increasing age and AJCC substage. Conditional survival estimates illustrate improved survival prospects for patients with cancer returning for follow-up and may define a finite period of increased risk after diagnosis.
The role of the glucocorticoid receptor (GR) in inhibiting chemotherapy-induced apoptosis in high-grade serous ovarian carcinoma (HGS-OvCa).
Authors: Erica Michelle Stringer, Maxwell N. Skor, Gini F. Fleming, Suzanne D. Conzen
Journal: Journal of Clinical Oncology (2013)

11101 Background: Ovarian cancer is the leading cause of death from gynecologic malignancies. High-grade serous ovarian cancer (HGS-OvCa) is often initially sensitive to platinum-based therapy, but relapse rates remain high. The TCGA recently found that HGS-OvCas have a gene expression and mutational profile similar to that of triple negative breast cancer (TNBC). Previously, our group demonstrated that dexamethasone treatment decreased chemotherapy-induced tumor cell apoptosis in TNBC and HGS-OvCa cell lines. We have also shown that glucocorticoid receptor (GR) activation induces expression of anti-apoptotic genes SGK1 and MKP1/DUSP1 in both HGS-OvCa and TNBC cell lines and in primary human ovarian and TNBC tumors. Methods: We examined glucocorticoid receptor (GR), estrogen receptor (ER), and progesterone receptor (PR) expression in a panel of HGS-OvCa cell lines by Western analysis and qRT-PCR. We also performed apoptosis assays with and without mifepristone, glucocorticoid and/or chemotherapy treatment using IncuCyte live-cell imaging technology in order to measure the effect of GR modulation of chemotherapy sensitivity. Results: HGS-OvCa cell lines (including CAOV3, HeyA8, SKOV3, Monty-1) all had detectable GR expression; HeyA8, SKOV3, and Monty-1 cell lines expressed very low levels of ER-alpha while all other HGS-OvCa cell lines did not express any detectable ER-alpha. Furthermore, none of the HGS-OvCa cell lines tested expressed PR.Apoptosis assays revealed that GR activation significantly inhibited gemcitabine/carboplatin-induced apoptosis in HGS-OvCa cell lines and that mifepristone could reverse this cell survival effect, presumably through GR antagonism. Conclusions: These results suggest that treatment with mifepristone, a GR antagonist, reverses GR-mediated cell survival signaling in HGS-OvCa and increases chemotherapy-induced tumor cell death. To further investigate the role of GR activity in HGS-OvCa, we are currently performing xenograft experiments with chemotherapy +/- mifepristone treatment.
Effect of zoledronate on persisting isolated tumor cells (ITC) in the bone marrow (BM) of patients without recurrence of early breast cancer
Authors: B. K. Rack, W. Janni, A. Schoberth, C. Schindlbeck, B. Strobl, T. Blankenstein, D. Rjosk, M. Heinrigs, H. Sommer, K. Friese
Journal: Journal of Clinical Oncology (2004)

9515 Background: Patients with persisting ITC in the BM after primary therapy show an increased risk for distant relapse and shortened survival (Janni et al., Cancer 2001; Wiedswang et al., SABCS 2003). Adjuvant chemotherapy, however, seems to have only limited effect on ITC in dormant state (Braun et al., 2000). Aim of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC in BM after completion of primary therapy. Methods: Zoledronate was applied at 4 mg q4wx6mon (loading dose 8mg) to 14 breast cancer patients with persisting ITC in the BM. Patients were to have completed surgery, leading to R0 resection and adjuvant chemotherapy for at least 6 months and had no evidence for recurrence at this point of time. In a matched pair analysis, these patients were compared to 14 patients with persisting ITC in the BM, who received no further therapy. The BM was re-examined after a median of 8 months (range 6.5–9.83) in the treatment group and 9 months (range 2.33–29.17) in the control group. ITC were detected by immunocytochemical staining using the pan-cytokeratin antibody A45-B/B3 and the APAAP technique. Results: Primary tumor characteristics, i.e. tumor size (P=.66), axillary nodal status (P=1.0) and histopathological grading (P=.76), as well as surgical (P=.23), adjuvant systemic (P=.10) and irradiation treatment (P=.36) were well balanced between both patient groups. While ITC were detected in all 28 patients at the time of first BM aspiration, no patient showed ITC in the BM following 6 months of zoledronate therapy. In contrast, persisting ITC were detected in 4 patients (29%) of the control group without treatment (P=.03). Conclusions: These preliminary results indicate potential antineoplastic effect of the cell-cycle independent agent zoledronate on persisting ITC in dormant state. In our view, these data provide a hypothesis generating basis to investigate the therapeutic efficacy of zoledronate on ITC in a secondary adjuvant setting by prospectively randomised trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis