tbuckley/cabot-search huggingface dataset:
Effect of chemotherapy on survival for intraductal carcinoma of the prostate (IDC-P) in patients with castration-resistant prostate cancer.
Authors: Akiyuki Yamamoto, Masashi Kato, Toyonori Tsuzuki, Momokazu Gotoh, Yoshihisa Matsukawa, Naoto Sassa, Tokunori Yamamoto
Journal: Journal of Clinical Oncology (2017)

e601 Background: Several studies have reported that intraductal carcinoma of the prostate (IDC-P) was a pathological adverse prognostic factor in patients with prostate cancer; however, there have been no reports regarding the effect of chemotherapy on survival for this group of patients. This study assessed the effect of chemotherapy on survival in patients with IDC-P. Methods: We retrospectively evaluated 150 prostate cancer patients who were initially diagnosed with distant metastases from June 2002 to January 2014 at the authors’ affiliated hospitals. All needle biopsy slides were reviewed by a single genitourinary pathologist according to the 2014 International Society of Urological Pathology (ISUP) grading system. Exclusion criteria were patients with missing data and those receiving local treatment. Seventy-nine patients with castration-resistant prostate cancer (CRPC) were analyzed. Study endpoints included cancer-specific survival after starting chemotherapy and survival duration from diagnosis of CRPC to cancer-related death. Log-rank test and the Cox proportional hazard model were used for statistical analysis. Results: The patients’ median age was 70 years (range 50–85 years). The median serum prostate-specific antigen level at initial diagnosis was 495.0 ng/mL (range 12.6–10,000). IDC-P was found in 62 out of 79 cases. Forty-six patients received docetaxel-based chemotherapy. Patients received a median of seven chemotherapy courses (range 1–55 courses). The cancer-specific survival duration after starting chemotherapy was 16.7 months in patients with IDC-P and 23.4 months in patients without IDC-P (P = 0.068). Chemotherapy could significantly extend survival duration from diagnosis of CRPC in patients with IDC-P (18.4 months vs. 4.4 months, P = 0.001) Conclusions: Although the effect of chemotherapy may be limited in patients with IDC-P, it significantly extended the time from diagnosis of castration-resistant disease to cancer-related death.
Risk factors for the incidence of breast cancer after prophylactic mastectomy.
Authors: Marion Kiechle, Larissa Thiem, Stefan Paepke, Johannes Ettl, Markus Niemeyer, Christoph Heitmann, Alfons Meindl, Axel Mario Feller
Journal: Journal of Clinical Oncology (2015)

e12545 Background: Prophylactic mastectomy (PM) is aneffective option in the prevention of breast cancer in women with BRCA1 and BRCA2 mutations. Aim of this retrospective study is to analyze the safety of the surgical procedure regarding complications and the incidence of breast cancer after PM. Methods: 104 women with BRCA mutations (71 BRCA1, 30 BRCA2, 3 BRCA1 and 2) undergoing PM were enrolled in this study and followed up for 3 years so far. 31 (30%) women had a primary PM (PPM) meaning that they were healthy at the time of surgery. 71 women (68%) were diagnosed with unilateral breast cancer and 2 women (2%) with bilateral breast cancer before (Secondary PM: SPM). The median age of breast cancer onset was 37.5 years. Results: Median age at the time of PPM was 39 and 41 years at SPM. 26 women additionally underwent PBSO with a mean age of 45 years. Most of the patients had a nipple sparing subcutaneous mastectomy (NSSM) with a flap (N = 52) or implant (N = 45) reconstruction. Only 7 of the diseased patients opted for mastectomy without reconstruction. 21% of the patients with implant reconstruction and 20% of the patients with flap reconstruction showed severe postsurgical complications such as necrosis and infection. 23% of the patients with an implant and 25% of the patients with a flap reconstruction needed a second surgery. In 7 out of 104 mastectomies (7%) an invasive carcinoma or DCIS was found histologically, whereas the majority occurred in patients (4/7) having had breast cancer before. During 4 years of follow up only 2 patients were diagnosed with a local breast cancer after SPM. The 2 patients had a NSSME with implant reconstruction. The recurrent disease was diagnosed 6 and 24 months after SPM and occurred only in BRCA 1 positive patients. Conclusions: This study shows for the first time, that women with BRCA mutations undergoing a secondary PM have a higher risk of developing breast cancer compared to women having a primary PM (2,7% vs 0%). Moreover, women with BRCA 1 mutations have a higher risk of developing breast cancer after SPM compared to BRCA 2 mutation carriers (2,7 % vs 0%).
The effect of different radiological models on diagnostic accuracy and lung cancer screening performance
Authors: Henry M Marshall, Henry Zhao, Rayleen V Bowman, Linda H Passmore, Elizabeth M McCaul, Ian A Yang, Kwun M Fong
Journal: Thorax (2017)

High false-positive (FP) scan rates associated with low-dose computed tomography (LDCT) lung cancer screening result in unnecessary follow-up tests and exposure to harm. The definition of a 'positive' scan can impact FP rates and screening performance. We explored the effect of Lung Imaging Reporting and Data System (Lung-RADS) criteria, PanCan Nodule Malignancy Probability Model and varying nodule size thresholds (≥4 mm, ≥6 mm, ≥8 mm) on diagnostic accuracy and screening performance compared with original trial definitions (National Lung Screening Trial (NLST) criteria) in a secondary analysis of a lung cancer screening cohort. We found Lung-RADS criteria and the PanCan Nodule Malignancy Probability Model could substantially improve screening performance and reduce FP scan rates compared with NLST definitions of positivity but that this needs to be balanced against possible risk of false-negative results. <h3>Trial registration number</h3> Australian New Zealand Clinical Trials Registry, ACTRN12610000007033.
Clinical profile and patterns of progression (PD) of patients (pts) with advanced nonsquamous non-small cell lung cancer (nsNSCLC) treated with first-line bevacizumab (B): AVVA study.
Authors: Javier De Castro, Manuel Domine, Jose Maria Garcia-Bueno, Salvador Saura, Ramon Garcia-Gomez, Maria Sereno, Oscar Juan, Eduardo Pujol, Belen Rubio, Manuel Cobo
Journal: Journal of Clinical Oncology (2012)

e18015 Background: B in combination with platinum doublets prolongs survival and delays PD in chemo-naïve pts with advanced nsNSCLC and its safety profile has been widely described in clinical trials. In this study we aim to evaluate the behavior, clinical profile and patterns of PD of real-life nsNSCLC pts treated with B in 44 Spanish institutions. Methods: AVVA is a multicenter, epidemiological study to define the clinical profile (gender, age, PS, histology, stage, comorbidities, tumor load, Tx, response and tolerability) and describe the patterns of PD. Pts diagnosed with advanced nsNSCLC and evidence of PD after treatment (Tx) with standard chemotherapy (CT) plus B up to 6 cycles followed by maintenance B were included. Results: Data of 158 pts are presented. Clinical profile was: median age 58 years (range 34-79); male 65%; stage IV 91%; adenocarcinoma 77%; ECOG PS 0/1/≥2 (%): 35/56/9; never/current/former smokers (%): 23/40/37. 64% of pts presented relevant concomitant disease at baseline (27% cardiovascular disease, 24% pulmonary disease). Tx received: B plus carboplatin-doublet/cisplatin-doublet/other (%) 70/25/5. Median no. of cycles for CT/B: 6/9. Patterns of PD: 44% presented high tumor load (tumor diameter ≥55mm and ≥5 lesions); 97% of pts presented intra-thoracic disease, 53% presented extra-thoracic disease and 13% only pulmonary disease. High tumor load was associated with extra-thoracic disease (p&lt;0.05). ORR was 53% (95% CI: 45-61) and disease control rate was 85%. Best response was achieved after a median of 4 cycles (range 1-16). ECOG 0/1 at PD (%): 15/50. Median PFS was 7.7 months (95% CI: 7.3-8.1). No differences were found in ORR or PFS according to tumor load and intra/extra-thoracic disease. Grade 3/4 toxicities were: venous thrombosis (3.2%/0), proteinuria (0.6%/0), hemoptysis (0.6%/0), pulmonary embolism (0/0.6%) and mucositis (0.6%/0). Conclusions: B was effective in this real-life patients’ population, irrespective of tumor load and location of the disease. These results confirm the well-established safety profile and the efficacy of B as frontline Tx in nsNSCLC.
Exploratory analysis of serum and urine biomarkers associated with chemotherapy-induced nausea and vomiting.
Authors: Hiroaki Akamatsu, Hirotsugu Kenmotsu, Keita Mori, Hisao Imai, Akira Ono, Yukiko Nakamura, Tateaki Naito, Haruyasu Murakami, Kenichi Suzuki, Toshiaki Takahashi, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2014)

e20716 Background: The risks of chemotherapy induced nausea and vomiting (CINV) have been identified from clinical factors. To date, the utility of serum and urine biomarkers associated with CINV have not been fully investigated. Methods: TRIPLE is a phase III study, which a novel 5-hydroxytryptamine 3-receptor inhibitor palonosetron (Palo) demonstrated a better control of delayed emesis compared with granisetron (Gra) in patients treated with highly emetogenic chemotherapy. Patients who participated in the TRIPLE study at our department were eligible for this analysis. Serum substance P (Sub P), ghrelin, 5-hydroxyindole acetic acid (5-HIAA) and urine 5-HIAA were collected on day 1 (before chemotherapy), 2, and 4, respectively. Results: Sixty-two patients were registered with one excluded due to deviation. All patients were treated with cisplatin (> 50mg/m2) containing regimens. Twenty-seven were allocated to the Palo arm, and 34 were to the Gra arm. Complete response during 120 hours post chemotherapy was slightly better in the Palo arm than the Gra arm in our cohort (59.3% vs 55.9%, p = 0.79, respectively). Between day 1 and 4, sub P and ghrelin were significantly decreased, while serum and urine 5-HIAA were significantly elevated. Between the treatment arms, Sub P was significantly decreased in the Palo arm, not in the Gra arm (p = 0.03, 0.20, respectively). Urine-5-HIAA was not significantly increased in the Palo arm, while a significant increase was shown in the Gra arm (p = 0.18, 0.03, respectively). With regard to serum 5-HIAA and ghrelin, these differences were not observed between the arms. Conclusions: Significant changes of serum and urine biomarkers were observed. Palo may affect in vivo kinetics of both Sub P and urine 5-HIAA in the delayed phase. Clinical trial information: 000006143.
Study evaluating possible causes of the normal variant 18F-FDG uptake in the thoracic spinal cord in patients without CNS malignancy.
Authors: Geetika Bhatt, Xiao-Feng Li, Vivek R. Sharma, Aashish D. Bhatt, Alex Cambon, Shesh Rai, Ali Cahid Civelek
Journal: Journal of Clinical Oncology (2012)

e21144 Background: Focal increased lower thoracic spinal cord 18F-FDG uptake is not infrequently observed and may be confused for spinal cord metastases. The cause of this physiological uptake is indeterminate though various theories have been postulated. We hypothesized that there may be a correlation between the thoracic (T11-T12) spinal uptake and lower limb movements or to bowel FDG activity. In the absence of paired FDG PET studies in same patients with and without leg movements we correlated the FDG uptake of the lower thoracic cord in ambulatory to that in bedridden patients. Methods: Sixty-three consecutive patients (12 bedridden) with 18F- FDG PET-CT with no known evidence of spinal cord or bony spine metastases were included. The SUV max/avg values of the liver, Thoracic: T11-T12 and Cervical: C3-C5 spinal cord segments and the bowel FDG activities of the ambulatory and bedridden patients were determined and compared. Statistical analysis was performed to evaluate various factors predictive of increased spinal cord FDG uptake. Results: Median age was 54 years (18- 93). Primary tumor histology was lung (21.8%), breast (9.3%), melanoma (15.6 %) and lymphomas (21.8%). The mean SUV max/avg values were liver (2.89/2.43); Thoracic cord (2.46/1.89); Cervical cord (2.25/1.82) and Bowel (4.4/2.9). Visible 18F-FDG thoracic spinal uptake was seen in 28%. Our analysis showed no significant correlation between the ambulatory status (p=0.219) or bowel FDG activity (p=0.210) and T11-T12 cord uptake. Conclusions: Although of no significance in this study, there might be a correlation between limb movements (amongst other factors) and physiological FDG uptake in the lower T-spine which warrants further dual studies in the same patient with and without leg motion. This may also help in differentiating normal variant spinal cord uptake from spinal cord metastatic lesions. [Table: see text]
Biomarker study evaluating the combination of dabrafenib (D) with trametinib (T) versus the combination after 8 weeks of monotherapy with dabrafenib or trametinib in patients with metastatic and unresectable stage IIIC or IV melanoma: GSK study 116613.
Authors: Christine Mateus, Emilie Routier, Severine Roy, Marina Thomas, Lise Boussemart, Isabelle Girault, Nathalie Chaput-Gras, Stephan Vagner, Hugo Cazenave, Lindi D Dalland, Mike R Lau, Maureen R Bleam, Anthony Michael D'amelio, Sylvie Pfersch, Caroline Caty, Caroline Robert
Journal: Journal of Clinical Oncology (2014)

TPS9114^ Background: Both D and T have demonstrated clinical activity as monotherapies and in combination in BRAF mutation–positive melanoma. However, the mechanism of acquired drug resistance and toxicity are not fully understood. We plan to investigate the sequential effects of BRAF and MEK inhibition on skin, blood, and tumor biomarkers, as well as to study correlations between biomarkers and response to treatment and toxicity. Methods: This is a 3-arm, open-label, randomized, phase 2 biomarker study in France, comparing the upfront combination of D with T versus their combination after 8 weeks of monotherapy treatment with D or T. As of the end of January 2014, 1 patient was randomized. Approximately 54 eligible patients, ≥ 18 years of age, with histologically confirmed stage IIIc or IV cutaneous melanoma and BRAF V600E/K mutation-positive disease will be randomized 1:1:1 to one of three treatment arms. In the monotherapy arms, treatment will be given for 8 weeks continuously (D 150 mg BID or T 2 mg QD) before other drug is dosed. In the combination arm, both drugs, at the respective doses above, will be given upfront. All treatments will be given until disease progression, death, or unacceptable toxicity. The primary objective of this trial is to evaluate biomarkers linked to treatment response, resistance, and toxicity when D and T are given as monotherapy and/or in combination. The secondary objectives are to evaluate the clinical response (overall response rate), as well as the exposures of the 3 arms in connection to clinical response and toxicity, and to characterize the safety profile of D and T in monotherapy and/or in combination. In addition, exploratory objectives are to evaluate changes in inflammation, the impact of the 2 drugs, separately and in combination, on the immune system, progression-free survival, and duration of response. The primary endpoint will be analyzed with a descriptive intent only. Hence, no hypothesis testing will be performed. Clinical trial information: EudraCT number 2012-004577-12.
A randomized, open-label, phase II study of MDV3100 alone or in combination with leuprolide and dutasteride as neoadjuvant therapy to prostatectomy in intermediate and high-risk prostate cancer.
Authors: Robert B. Montgomery, Anthony Joshua, Alison L. Hannah, Amy C. Peterson, Christian Lopez, Martin Edwin Gleave, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2012)

TPS4695 Background: MDV3100 is a potent androgen receptor (AR) signaling inhibitor (ARSI) that inhibits AR signaling via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation, and inhibition of nuclear AR-DNA binding. In vivo, MDV3100 induces significant prostate cancer apoptosis, an effect not seen with anti-androgens. To date, the use of neoadjuvant androgen deprivation therapy has not led to an improvement in time to PSA progression (Soloway 2002; Aus 2002). While serum androgens may be suppressed using luteinizing hormone-releasing hormone agonists, intratumoral levels of androgens remain, driving continued AR signaling and prostate cancer survival. More effective inhibition of AR signaling may improve local and systemic disease control. Methods: MDV3100-07 will assess the effect of 6 mos of neoadjuvant AR blockade with AR inhibition alone (MDV3100) or in combination with maximal suppression of androgens (MDV3100 +leuprolide [L] + dutasteride [D]). Eligible patients will have treatment-naive localized prostate cancer and be candidates for radical prostatectomy. Patients must have either PSA &gt; 10 ng/mL or Gleason score ≥ 7 (4 + 3) with ≥3 cores containing tumor. Patients with evidence of metastatic/nodal disease are excluded. All patients receive MDV3100 (160 mg/d PO); those randomized to MDV3100+L+D therapy also receive L (22.5mg IM q3m) and D (0.5 mg/day PO). Serum/tumor androgen levels will be serially assessed. Tissue from the diagnostic and prostatectomy specimens will be evaluated for androgen levels, AR signaling profiles, and selected markers of apoptosis and mitotic indices. The primary efficacy endpoint is pathological complete response (pCR) rate at time of radical prostatectomy. For each arm, the percent of patients who achieve a pCR will be compared to the percent pCR in patients treated with neoadjuvant leuprolide, estimated to be 5% in a mixed low-to-intermediate risk population. Target Accrual: 40 pts will be randomized 1:1 to MDV3100 or MDV3100+L+D therapy. Keywords:MDV3100, prostate cancer, androgen receptor, anti-androgen, Phase 2, neoadjuvant.
Tissue Sample Collection, Processing, Storage, Archiving and Usage in the Leukemia Tissue Bank: an M. D. Anderson Experience
Authors: Jairo Matthews, Sarah Gwen Pelletier, Katie Gaw, Kavita Chauhan, Wilmer Flores, Manasi Chauhan, Giang Hoang, Elizabeth Graver, Jahn Laurel, Deanna Alexander, Sherry Pierce, Steven M. Kornblau
Journal: Blood (2016)
Evaluating preliminary outcomes among primary care and oncology providers who participated in the cancer survivorship e-learning series for primary care providers.
Authors: Mandi Pratt-Chapman, Aubrey Villalobos, Allison Harvey, Ashley Roccio
Journal: Journal of Clinical Oncology (2017)

78 Background: The American Cancer Society estimates there are 15.5 million cancer survivors in the U.S. and projects this number will rise. Survivors are at increased risk for a variety of issues due to cancer and its treatment including long-term and late effects. In recent years, there has also been increased focused on ensuring coordinated care for survivors to address these and other issues. Methods: Launched in 2013, the E-Learning Series evaluation employs self-report pre/post surveys using a 5-point Likert scale of agreement. In an initial analysis conducted with available data, participants who took more than one module were represented more than once in the total sample. Independent samples t-tests and Mann Whitney U tests were used for tests of significance for comparisons between PCP and oncology providers. Results: Of the respondents (n = 1,662), PCPs were represented on average 30% across modules. Both PCP and oncology providers reported knowledge gains across modules from pre (Mean pre-range for PCP = 2.96-3.71, SD = 0.797-1.022; Mean pre-range for oncology = 3.28-3.92, SD = 0.717-0.964) to post (Mean post-range for PCP = 4.05-4.44, SD = 0.568-0.716; Mean post-range for oncology = 4.28-4.49, SD = 0.525-0.611). Mean change scores for PCPs ranged from 0.66-1.15 (SD = 0.671-1.093) and for oncology providers change scores ranged from 0.58-1.04 (SD = 0.700-0.967). Related to shared-care model, differences in perceived knowledge gain about treatment late effects were statistically significant (p = 0.001) between PCPs (change score mean = 0.92, SD = 0.975) and oncology providers (change score mean = 0.58, SD = 0.799). Differences were also seen in rehabilitation module, with PCPs indicating gain in ability to identify appropriate interventions (p = 0.047). Conclusions: Initial results indicate the E-Learning Series is effective in improving knowledge about needs of survivors as well as recommended care practices among providers.
A phase I study of high-dose calcitriol in combination with temozolomide for patients (Pts) with metastatic melanoma (MM).
Authors: Erin Pettijohn, Alfred Rademaker, Brenda K. Martone, Erica Poast, Bing Bing Weitner, John W. Eklund, Timothy Kuzel
Journal: Journal of Clinical Oncology (2013)

9087 Background: Temozolomide (Tem) has demonstrated efficacy as an oral alternative for pts with MM on traditional and extended dosing schedules. Calcitriol has known antiproliferative properties in vitro, and has shown synergistic effects with chemotherapy. Additionally, vitamin D receptor (VDR) polymorphisms are associated with alterations in melanoma susceptibility and disease progression. Specifically, the VDR genotype tt/ff (Taq1 and Fok1 polymorphisms) has been associated with tumors &gt;3.5mm, though no studies have focused on survival. Methods: Tem 150mg/m 2 was administered on days 2-8 and 16-22 every 28 days until progression or significant toxicity. Calcitriol was given on days 1 and 15 every 28 days with 3 pts at a dose of 0.2mcg/kg, 3 pts at 0.3mcg/kg, 3 pts at 0.5mcg/kg, and an additional 11 pts at a maximum dose of 0.5mcg/kg. VDR gene analysis was completed on 17/20 pts using PCR-RFLP based assays. Tolerability was the primary objective with secondary objectives of time to progression (PFS) and overall survival (OS), both as a whole and by VDR genotype. Results: Twenty pts (males=15) with MM treated with at least one prior systemic therapy or who were not candidates for interleukin-2 (conducted pre BRAF and anti CTLA agents), were accrued. Median age was 58. The regimen was well-tolerated with leukopenia, lymphopenia, thrombocytopenia, anemia, and thrombosis as the most common grade 3 or 4 toxicities at 10% incidence each, less than observed in prior studies (Patel et al Eur J Ca 2011). Obj RR was 10%. Median PFS was 1.8 mo with a mean of 2.7 cycles given. Pts with low-risk VDR genotype non-tt or ff (n= 11) had a median OS of 7.4 mo compared to 3.8 mo for tt or ff or both (n=6)(median ratio=1.95) from time of enrollment, although not statistically significant given small sample sizes. Conclusions: The extended dosing of Tem with calcitriol is a well-tolerated oral regimen in MM. The trend toward improved OS in non-tt/ff VDR genotypes is consistent with prior studies associating the tt/ff genotype with biologic aggressiveness. Whether this represents a benefit of the inclusion of calcitriol should be studied further. Clinical trial information: NCT00301067.