tbuckley/cabot-search huggingface dataset:
Use of cold cap in cancer patients: A single institution experience.
Authors: Emmet Jordan, Marvin Chang Jui Lim, Siobhan Lovett, Raymond S. McDermott, Janice Maria Walshe
Journal: Journal of Clinical Oncology (2014)

e20656 Background: Alopecia induced by chemotherapy is a distressing side effect. It can have negative effects on patients' self-esteem, body image and adversely influence choice of chemotherapeutic agent. Circumventing chemotherapy induced hair loss (CIHL) in patients is therefore beneficial. The cold cap (CC) system has been shown to be effective in CIHL especially when alopecia causing agents like taxanes and anthracyclines are used. CC use has been controversial with reports of scalp metastases development; this may affect its use in the oncology community especially in the adjuvant setting due to a lack of knowledge and experience. Its use in the oncology setting in Ireland is limited. We evaluated CC use in a single institution in Ireland. Methods: Patients (pts) who received the CC system from January 2007- November 2013 were evaluated. Clinicopathological data collected included age, gender, disease morphology and stage. We also evaluated for scalp metastases and relapse. Results: 83 pts were identified. 8/83 (9.6%) were male. Most common cancers were: breast n=53 (63.9%), gastric n=8 (9.6%), colon n=6 (7.2%), prostate n=5 (6.0%), lung n=3 (3.6%), adrenal n=2 (2.4%). Ovarian, penile, pancreas, oesophagus, renal and sarcoma n=1 (1.2%). Median age was 55 years (range 20-76 years). 34/83 (40.9%) had metastatic disease. 40/53 breast cancer (BC) pts were treated in the adjuvant setting. BC subtypes were 11(20.8%) HR+/HER2+; 32 (60.4%) HR+/HER2-; 3 (5.7%) HR-/HER2+; and 7(13.2%) were HR-/HER2-. BC were high (n=25, 47.1%) or intermediate histologic grade (n=19, 35.8%). 81 chemotherapeutic regimens were available - 58/81 received taxane, 6/81 anthracycline plus taxane, 7/81 anthracycline, 7/81 irinotecan, 2/81 etoposide and 1/81 cabazitaxel. 0/83 (0%) pts developed scalp metastases. 83/83 completed therapy with CC. 4/53 adjuvant BC pts developed metastatic disease. 4/4 were HR+/HER2- pts, median relapse time from diagnosis was 25 months (range 11-34 months). Metastatic sites were liver n=3, brain n=2, lung n=1. Conclusions: CC treatment in preventing CIHL is tolerable. It can be used in the adjuvant and metastatic setting. An increased risk of scalp metastases was not seen. CC provides a valid option in patients treated with alopecia causing agents.
The effect of body mass index (BMI) on non-small cell lung cancer (NSCLC) mortality.
Authors: Taher Abu Hejleh, Elizabeth A. Chrischilles, Jane F. Pendergast, Grelda Yazmin Juarez, Robert B. Wallace
Journal: Journal of Clinical Oncology (2014)

e19041 Background: High BMI is associated with increased mortality in many cancers. However, the effect of BMI on survival in NSCLC is less established. In this study, we explored the effect of weight loss prior to diagnosis and BMI at diagnosis, on NSCLC mortality. Methods: This study utilizes the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium database. Clinical and demographic variables and survival measures were obtained from patient surveys and abstracted medical records. BMI at diagnosis was categorized into five groups: <18.5, 18.5–24.9, 25.0–29.9, 30–34.9, and ≥35. Weight loss percentage over the year prior to diagnosis was calculated using the actual weight at diagnosis and the patient recalled weight one year prior to diagnosis. This was categorized into <10% and ≥10% loss of body weight in the year prior to cancer diagnosis. The association of BMI categories with survival was assessed using a log-rank test, and the Cox proportional hazard model was used to model survival adjusting for BMI at diagnosis, weight loss percentage over 1 year prior to NSCLC diagnosis, history of smoking and other variables associated with survival in NSCLC. Results: A total of 2,524 NSCLC patients were included in the analysis. Of these, 45% had a BMI of 18.5-24.9 at diagnosis. Weight loss 1 year prior to diagnosis differed among BMI categories (P <0.0001), with a higher proportion of patients who had a BMI <18.5 at diagnosis and also lost significant weight (≥10% of baseline weight). On univariate survival analysis, patients with BMI ≥35 at diagnosis of NSCLC survived the longest among the other BMI categories (median survival time was 37.5 months (Log Rank Test: P<0.0001). Cox proportional hazard model showed worse survival for patients with BMI <18.5 (HR:1.61, 95% CI: 1.20-2.16) and those who lost ≥10% of their body weight over the year prior to diagnosis (HR:1.45, 95% CI: 1.24-1.71). Conclusions: BMI <18.5 at diagnosis of NSCLC, and loss of ≥10% of body weight in the year prior to diagnosis were associated with increased mortality in all stages of NSCLC. BMI >25, including BMI ≥35, was not associated with increased mortality. Clinical trials are needed to assess if interventions to reverse weight loss and aiming for a higher BMI could prolong survival.
Impact of adjuvant therapies on treatment outcomes for patients with resected gallbladder cancer and changes in treatment patterns in the United States over the past decade: An analysis from the National Cancer Data Base.
Authors: Timur Mitin, C. Kristian Enestvedt, Ahmedin Jemal, Helmneh M. Sineshaw
Journal: Journal of Clinical Oncology (2017)

391 Background: There are no randomized data to guide clinicians treating patients with gallbladder cancer (GBC). Several retrospective studies reported the survival benefits of adjuvant radiotherapy (RT) and chemoradiation (CRT). The aims of this study were to examine whether these publications have impacted the utilization of adjuvant therapies and whether their survival benefits were evident in contemporary cohort of patients. Methods: Using the National Cancer Data Base, we identified 5,029 patients diagnosed with T1-3N0-1 GBC and treated with surgical resection from 2005 to 2013. We described trends in receipt of adjuvant treatments for three time periods (2005-2007, 2008-2010, 2011-2013) and calculated 3-year overall survival (OS) probabilities for 2,989 patients treated in 2005-2010. Results: The percentage of patients who received no adjuvant treatment was unchanged from 2005 to 2013. Adjuvant RT decreased from 4.3% to 1.7% (p &lt; 0.01), adjuvant chemotherapy increased from 8% to 14% (p &lt; 0.01), and adjuvant CRT remained stable at 16% (p = 0.98). Even for locally advanced disease (T3N0 and T1-3N1) or in the setting of positive resection margins, over 50% of patients in US did not receive adjuvant treatments. Adjuvant treatments were associated with improved 3-year overall survival in patients with resected GBC, as listed in Table. Adjuvant CRT was associated with improved survival in all stages, except T1N0, and in patients with negative and positive margins. Conclusions: Over the past decade there was no increase in the utilization of adjuvant therapies in the US for patients with resected GBC. Adjuvant therapy is associated with significantly improved 3-yr OS. In the absence of randomized data, this analysis should form the basis for clinical recommendations and national guidelines should be amended to support adjuvant treatment.[Table: see text]
Safety report of a phase II trial of irinotecan plus S-1 (IRIS) with cetuximab in patients with KRAS wild type of metastatic colorectal cancer: HGCSG0902.
Authors: Yoshito Komatsu, Satoshi Yuki, Takashi Kato, Ayumu Hosokawa, Ichiro Iwanaga, Osamu Muto, Kazuteru Hatanaka, Michio Nakamura, Yasushi Tsuji, Yuh Sakata
Journal: Journal of Clinical Oncology (2012)

e14062 Background: IRIS is one of the standard regimens as second line treatment in metastatic colorectal cancer since IRIS demonstrated the non-inferiority to FOLFIRI (FIRIS study) in Japan. We previously presented IRIS plus bevacizumab (ESMO 2010), however; there is still lack of combination data of IRIS plus molecular target drugs. Thus we conduct the study of IRIS plus cetuximab (HGCSG0902) and this is the planned safety analysis for first 20 patients. Methods: HGSCG0902 is a multicenter phase ll study. Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS wild type. Patients (pts) received S-1 80-120 mg/m 2 /day p.o. on days 1-14 and irinotecan 100mg/m 2 on days 1 and 15 repeated 28 days. Cetuximab administrated 400mg/m 2 loading dose and continued 250mg/m 2 every week or 500mg/m 2 bi-weekly. The primary endpoint was response rate and the secondary endpoints were disease control rate, PFS, OS and safety. Results: Demographics of the 20 enrolled pts were male/female: 13/7, median age: 64.5, colon/rectal: 13/7, PS0/1: 12/8, prior bevacizumab +/-: 15/4 pts. Cetixumab were administrated weelkly/bi-weekly: 9/11 pts. 70% of pts had adverse events (AE). The most common non-hematological AE were diarrhea (85%), acne-like rash (80%), fatigue (75%) and anorexia (60%) and hematological AE were anemia (90%), AST increase (75%) and ALT increase (70%). The main grade 3-4 AE were diarrhea (45%), acne-like rash (20%), anorexia (20%) and stomatitis (20%). These AE were as expected. Nineteen pts stopped the treatment due to progression (52.6%) and AE (36.8%). Conclusions: This safety analysis suggests that IRIS plus cetuximab is well-tolerated and easy to administer.
Phase II trial on cisplatin-doxorubicin hydrochloride-paclitaxel (TAP) combination as neoadjuvant chemotherapy (NACT) for locally advanced cervical adenocarcinoma (LACA).
Authors: Francesco Raspagliesi, Stefano Ramondino, Flavia Zanaboni, Antonino Ditto, Eugenio Solima, Barbara Grijuela, Gian Battista Spatti, Massimo Gabbanini, Maria Mancini, Fabio Martinelli, Carla Amaya De Carrillo, Rosanna Fontanelli, Domenica Lorusso
Journal: Journal of Clinical Oncology (2012)

5096 Background: NACT followed by surgery is a different therapeutic approach to locally advanced cervical cancer that seems to offer specific advantages over chemoradiation such as potential activity against distant micrometastases, a debulking effect improving subsequent surgical outcome, less toxicity, and an easier management of salvage therapy. This phase II trial was designed to evaluate the toxicity and activity of NACT with TAP in patients with LACA. Methods: Patients (pts) with FIGO stage IB2 (9 pts)- II (21 pts) uterine adenocarcinoma were treated with cisplatin 70 mg/mq, doxorubicin hydrochloride 45 mg/mq and paclitaxel 150 mg/mq day 1 every 21 days for 3 cycles. Eight pts (26.6%) presented with positive lymphnodes ( +LY) at diagnosis (5 pelvic and 3 pelvic+paraortic). After the last cycle of chemotherapy patients underwent radical surgery with lymphnode dissection. Clinical responses to chemotherapy was evaluated according to Recist criteria. Pathological response was classified as no residual tumor (pCR), residual disease with &lt;3 mm stromal invasion (pR1) or residual disease with &gt;3 mm stromal invasion (pR2). Due to the slow accrual the trial was closed before the target population of 45 pts was reached. Results: Between 2003 to 2010, 30 women were enrolled. Two complete clinical responses (6.7%), 21 partial responses (70%) and 7 stabilizations of disease (23.3%) were registered. All the patients underwent radical surgery and were assessable for pathologic responses. Five patients (16.6%) achieved a pCR , 8 (26.6 %) a pR1 response; 17 patients (56.7%) a pR2 response. At pathological assessment 10 pts (33.3%) presented with +LY (7 pelvic, 1 paraortic, 2 pelvic+paraortic). At a median follow up of 45 months progression free survival and overall survival were 37 months (95% CI 1-98) and 45 months (95% CI 9-101+) respectively. Hematologic toxicity was the most relevant side effect with 13 pts (43 %) reporting grade 3-4 neutropenia. Conclusions: The TAP combination seems to be feasible with an acceptable toxicity profile and a promising response rate for the treatment of LACA. The effect of NACT on lymphnodes status warrant further investigation.
Upstream MAPK pathway inhibition: MEK inhibitor followed by a BRAF inhibitor in advanced melanoma patients.
Authors: Simone M. Goldinger, Carla Murer, Pascale Stieger, Reinhard Dummer
Journal: Journal of Clinical Oncology (2013)

9071 Background: The presence of activating BRAF mutations in about 60% of all metastatic melanomas (mM) has led to the development of inhibitors (i) targeting the RAF and MEK kinases. MEK is the downstream effector of BRAF. However, the blockage of the MAPK pathway is limited due to the development of resistance mechanisms. MEK resistance can confer cross-resistance to BRAF inhibition, whereas BRAF resistance is independent from the MAPK pathway. Hence, it seems reasonable to start a MAPK pathway inhibition by a BRAFi. An upstream inhibition beginning the treatment reversed with a MEKi followed by a BRAFi has not yet been clinically explored. Methods: Patients at the Dermatology Department of the University Hospital of Zurich with mM harboring a BRAF mutation formed the study cohort. Patients were divided into a group who was treated initially with a BRAFi (vemurafenib or LGX818) followed by a MEKi (AZD6244, trametinib, or MEK 162), and a group who first received a MEKi and was later treated with a BRAFi. Duration of disease control (DDC) was measured in time from the initiation of the treatment to discontinuation due to disease progression or toxicity. Results: A total of 16 patients (7 females, 9 males, age 30-73 years) with BRAF mutated mM were evaluated. The median DDC (mDDC) was similar in both groups. When patients were treated first with a BRAFi (n=7), the mDDC for BRAFi was 7.6 and for MEKi 1.7 months, respectively. In contrast, when the treatment sequence was inversed (n=9), the mDDC for MEKi was 3.9 and for BRAFi 4.7 months. We observed some benefit (partial response, stable disease) using chemotherapy after BRAFi/MEKi progression. Conclusions: This analysis indicates that the sequential MEK-RAF inhibition of the MAPK pathway is acceptable in BRAF mutant mM patients. The sum of the DDC of both groups (9.3 and 8.6 months) is comparable to the promising BRAFi/MEKi combination therapy (median PFS 9.4 months). Besides the sequenced administration analyzed here, an intermittent administration should be further studied.
Validation of postinduction Curie scores in high-risk neuroblastoma.
Authors: Gregory A Yanik, Arlene Naranjo, Marguerite T Parisi, Barry L. Shulkin, Helen R Nadel, Michael J Gelfand, Ruth L Ladenstein, Ariane Boubaker, Ulrike Poetschger, Bieke Lambert, Maria Rita Castellani, Dominique Valteau-Couanet, Susan G. Kreissman, Julie R. Park, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2014)

10031 Background: A semi-quantitative MIBG scoring method (Curie scoring, CS) has been previously examined in the Children’s Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a post-induction CS >2 associated with poor event-free (EFS) and overall survival (OS). We now examine the impact of Curie scoring in an independent data set, the SIOPEN-HR-NBL1 (SIOPEN-NB) high-risk study. Methods: MIBG scans from patients with MIBG avid, INSS stage 4 neuroblastoma enrolled on SIOPEN-NB were evaluated at diagnosis (n=345) and post-induction (n=330). Scans were evaluated in 10 different anatomic regions by 2 reviewers, including 9 skeletal and 1 soft issue region, with each region scored 0-3 based upon disease extent, and a cumulative consensus score generated. Optimal cut-points at diagnosis (Dx) and post-induction were determined using the Youden index, with outcomes determined. Curie scores from patients enrolled on COG A3973 at diagnosis (n= 280) and post-induction (n= 237) were used for comparison. Results: The optimal CS cut-points at Dx were 12 in SIOPEN-NB and 9 in COG A3973. There was a significant outcome difference by CS (≤ 12 vs > 12) at Dx [5-yr EFS: 43.0±5.7 vs 21.4±3.6%, p<0.0001] in the SIOPEN-NB cohort. By comparison, CS at Dx were not prognostic in COG A3973, with no outcome difference identified at any cut-point. The optimal CS cut-point post-induction was 2 in both SIOPEN-NB and COG A3973, with a post-induction CS > 2 associated with inferior outcomes (Table). A post-induction CS > 2 carried prognostic significance for both MYCN amplified and MYCN non-amplified tumors, in both COG A3973 and SIOPEN-NB. The Curie score at Dx and post-induction maintained independent statistical significance in Cox models when compared to standard predictive covariates age and MYCN. Conclusions: The prognostic significance of post-induction Curie scores has now been validated in an independent cohort of patients, with a post-induction Curie score > 2 associated with inferior outcome in two cooperative group trials, SIOPEN-HR-NBL1 and COG A3973. No. Post-induction Curie score 5-year EFS (± SE) 5-year OS (± SE) CS ≤ 2 CS > 2 p CS ≤ 2 CS > 2 p SIOPEN 330 39.2 ± 4.7 16.4 ± 4.2 <0.001 48.0 ± 4.7 29.5 ± 5.1 <0.001 COG 237 42.0 ± 5.8 10.5 ± 10.0 <0.001 55.4 ± 6.3 26.7 ± 11.4 0.02
Abstract 108: Glycolysis, Cardioprotection and Their Modulation by Differential Interactions of Hexokinase I and II with Mitochondria
Authors: Guillaume Calmettes, Scott John, James N Weiss, Bernard Ribalet
Journal: Circulation Research (2012)

Rationale: Neonatal heart is more glycolytically active and less susceptible to anoxia/reoxygenation injury than adult heart. Hexokinase (HK) is the first step in glycolysis and its binding to mitochondria is known to be cardioprotective. Since neonatal cardiac myocytes mainly express the HKI isoform, whereas HKII predominates in adults, we explored the functional consequences of such difference. Objective: To investigate whether differential interactions of HKI and HKII with mitochondria in neonatal (NRVM) and adult rat ventricular myocytes (ARVM) account for their different metabolic profiles and susceptibility to anoxia/reoxygenation injury. Methods and Results: We performed real-time imaging in isolated NRVM and ARVM expressing the genetically-encoded biosensors FLIPglu-600µM to track intracellular glucose metabolism and YFP-tagged HK constructs to track subcellular HK localization, together with a propidium iodide-based cell death assay. We show that HKI remains bound to mitochondria in both NRVM and ARVM, while HKII distributes between the mitochondria and cytoplasm. Extracellular glucose removal displaced HKII from mitochondria in ARVM, but not in NRVM, whereas iodoacetate (IAA) displaces HKII in both. These differences were associated with a 35-fold greater glycolytic activity and markedly enhanced resistance to anoxia/reoxygenation injury in NVRM. NRVM became comparably susceptible to anoxia/reoxygenation injury only when treated with IAA to suppress HK interaction with mitochondria (whereas glucose removal alone had no effect). Conclusions: HKs exhibit stronger interaction with mitochondria in NRVM, accounting for their enhanced glycolytic activity and increased resistance to anoxia/reoxygenation injury. HKI may be superior to HKII in protecting the heart because of its stronger interaction with mitochondria.
Less than half of new mothers in England breast feed after two months
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Public Health England has launched a 24 hour chat room to try to improve rates of long term breast feeding, after a survey found that women have many unanswered questions about breast feeding.

In a new survey of 500 mothers of young children the public health agency found that almost three quarters (74%) agreed that breast feeding can be painful, and a similar proportion (71%) said that breast feeding would prevent them from taking medicine.

More than half (54%) of the …
Genomic characterization of long-term responders to olaparib.
Authors: Stephanie Lheureux, Jonathan A. Ledermann, Sarah Runswick, Darren R Hodgson, Kirsten Timms, Jerry S. Lanchbury, Stanley B. Kaye, Charlie Gourley, David Bowtell, Elise C. Kohn, Clare L. Scott, Ursula Matulonis, Tony Panzarella, Brian Andrew Dougherty, J Carl Barrett, Zhongwu Lai, Mark o'Connor, Jane D. Robertson, Tony Weishiu Ho, Amit M. Oza
Journal: Journal of Clinical Oncology (2015)

5566 Background: BRCA1/2 mutations (BRCAm) predict benefit from olaparib (vs placebo) in platinum sensitive high grade serous ovarian cancer (HGSOC). However not all patients (pts) with BRCAm respond and others without BRCAm have very durable benefit from PARP inhibitors. This study characterised long (LT ≥ 2 years) and short-term (ST ≤ 3months) responders on olaparib maintenance. Methods: Clinical (previous chemo lines, stage, platinum free interval) and molecular variables from archival tumor were assessed from study D0810C000019 – olaparib/placebo after response to platinum in HGSOC. Germline BRCA1/2 testing, Homologous Recombination Deficiency (HRD) score (positive ≥42) and BRCA1 methylation were determined by Myriad Genetics. A comprehensive genomic profile with next generation sequencing was performed through Foundation Medicine. Fisher’s exact test was used to test the association between presence and absence of any factor comparing ST vs LT. Results: Of pts who received olaparib maintenance, 32 had LT and 21 ST disease control. In the LT group, 21 pts had BRCAm (66%, BRCA1 9 pts, BRCA2 12 pts), positive HRD scores and deleterious TP53 mutations. Variants of Unknown Significance were found in 2 LT pts (6%) with positive HRD scores and TP53 mutations but negative for BRCA1 methylation. In the overall study population, BRCA1 methylation was not observed within LT pts: 27/37 LT pts (olaparib/placebo) had BRCA1 methylation status available and none were methylated. 42/61 ST pts had methylation status available and 8 (19%) had BRCA1 methylation. Complete response at the time of olaparib maintenance (p=0.026) and HRD deficiency status (p=0.026) were associated with LT on univariate analysis, and did not discriminate ST vs LT in the placebo group. LT group showed a trend for the presence of deleterious TP53 mutation (p=0.051); TP53 mutation status was available in 28/32 LT and 16/21 ST; deleterious mutations were detected in 27/28 LT vs 12/16 ST pts; in contrast with TP53 wild-type found in 1/28 LT pt and 4/16 ST pts. Conclusions: Comparison of LT and ST responders provides a contrasting assessment of the intersection of disease biology on effect of olaparib and may allow identification of predictive patterns of durable benefit that need to be validated.