tbuckley/cabot-search huggingface dataset:
Dose tailoring of breast cancer adjuvant chemotherapy aiming at avoiding both over and undertreatment: Results from the prospective PANTHER study.
Authors: Alexios Matikas, Theodoros Foukakis, Volker Moebus, Richard Greil, Nils-Olof Bengtsson, Guenther G. Steger, Michael Untch, Hemming Johansson, Mats Hellstrom, Per Malmström, Michael Gnant, Sibylle Loibl, Jonas C. S. Bergh
Journal: Journal of Clinical Oncology (2018)

538 Background: Adjuvant breast cancer chemotherapy (ACT) improves relapse free (BCRFS) and overall survival (OS). Differences in terms of efficacy and toxicity could partly be explained by the significant interpatient variability in pharmacokinetics which cannot be captured by dosing according to body surface area. Consequently, tailored dosing was prospectively evaluated in the phase III PANTHER trial with 2017 patients. Methods: PANTHER is a multicenter, open-label, randomized phase III trial which compared tailored, dose dense epirubicin/cyclophosphamide (EC) and docetaxel (D) (group A) with standard interval 5-fluorouracil/E/C and D (group B), with identical duration of therapy in both arms. The primary endpoint was BCRFS. The primary efficacy analysis revealed an improved event free survival and favorable trends for BCRFS, OS and distant disease free survival compared with standard ACT. In this secondary analysis, we aimed to explore the concept of dose tailoring. Our two hypotheses regarding patients treated at group A were that BCRFS would not differ according to the cumulative administered dose; and that dose tailoring would lead to appropriate dosing and improved outcomes for obese patients. Results: Patients randomized in group A had similar BCRFS regardless of the cumulative epirubicin (p = 0.495) or docetaxel dose (p = 0.575). There were consistent, non-statistically significant trends in favor of patients receiving < 360 mg/m2 epirubicin compared to 360-420 and > 420 mg/m2. In addition, there were no differences in outcomes between patients receiving tailored ACT with a body mass index (BMI) of < 24 (n = 307), 24-28 (n = 296) and 28-40 (n = 312) (p = 0.384). Patients with a BMI of 28-40 had a non-significant trend for improved BCRFS, using BMI < 24 as reference (HR = 0.73, 95% CI 0.45-1.18) Conclusions: Dose tailoring could spare patients from unnecessary overdosing without compromising outcomes and may overcome the negative impact on prognosis conferred by obesity. Although exploratory, these results highlight the feasibility of tailored ACT, and underscore the need for further studies. An in-depth discussion will be presented at the ASCO meeting. Clinical trial information: NCT00798070.
Breast Cancer Index (BCI) and prediction of pathological complete response (pCR) to neoadjuvant chemotherapy in estrogen receptor positive (ER+) breast cancer.
Authors: Laura Spring, Yi Zhang, Kai Treuner, Hannah Park, Megan Yuen, Beverly Moy, Catherine A. Schnabel, Fabrice Andre, Aditya Bardia
Journal: Journal of Clinical Oncology (2018)

576 Background: Although endocrine therapy is the mainstay of management of ER+ tumors, optimal neoadjuvant strategy for ER+ breast cancer is unclear, and improved selection of patients for neoadjuvant chemotherapy (NACT) vs neoadjuvant endocrine therapy are critical ongoing questions. BCI is a gene expression signature that stratifies patients for risk of overall (0-10y) and late (post-5y) distant recurrence and the likelihood of benefit from extended endocrine therapy. Given BCI's proliferation (MGI) and estrogen-related (HoxB13/IL17BR) activities, this study investigated its ability to predict pCR in ER+ breast cancer patients treated with NACT. Methods: BCI analysis was performed on pre-treatment core biopsies from patients with ER+ breast cancer treated with NACT at Massachusetts General Hospital (n = 84) and Institut Gustave Roussy (n = 101). pCR and overall survival were collected from charts by investigators blinded to the BCI results. Multivariate logistic regression and Cox proportional hazards regression were used to evaluate the association of BCI risk categories with pCR and overall survival. Results: Patients (N = 185; 100% ER+/HER2-, 56% N+, 65% T2, 49% grade 2) were treated with NACT, mostly anthracycline/taxane-based regimens, and 10 (5.4%) achieved pCR. BCI was significantly associated with pCR, with no pCR observed in the low risk group (P = 0.0003). BCI was the only significant predictor of pCR in multivariate analysis including tumor size, tumor grade, PR status, and nodal status (OR = 14.0 [95% CI 1.19 – 263.5], P = 0.05). BCI was also a significant predictor of overall survival in these patients following NACT (P = 0.008). Conclusions: Pre-treatment BCI significantly predicted response to neoadjuvant chemotherapy in ER+ breast cancer patients. Results of this study suggest potential clinical utility of BCI in stratifying ER+ patients with chemo-sensitive disease, while considering alternative treatment strategies such as neoadjuvant endocrine therapy for women who may not respond adequately to NACT and potentially avoid toxicity associated with NACT.
Art dealing: raffle tickets fund pill testing at festivals
Authors: Richard Hurley
Journal: BMJ (2018)

HAITHAM IMAD/EPA-EFE/REX/Shutterstock

An anonymous contemporary artist, Chemical X, has used 4111 pills of what appears to be the illegal party drug ecstasy to create this work of art, entitled Rush .

The piece has been valued at £50 000 (€57 000; $67 000), but the artist is offering it as a prize in a raffle, with the proceeds from the £2 tickets being donated to the Loop, an organisation that offers testing of illegal drugs with the aim of reducing harm.

The Loop runs pop-up laboratories in city centres, …
Tumor characteristics and treatment in early-onset colorectal cancer.
Authors: Andrea Burnett-Hartman, John D. Powers, Jessica Chubak, Douglas Corley, Nirupa R. Ghai, Carmit K. McMullen, Pamala A. Pawloski, Heather S. Feiglelson
Journal: Journal of Clinical Oncology (2018)

566 Background: While overall incidence and mortality of colorectal cancer (CRC) has declined, incidence and mortality are increasing in those &lt; 50 years old (early-onset CRC). Our objective was to better understand early-onset CRC by comparing tumor characteristics and initial treatment type between early-onset and normal/late-onset CRC. Methods: We used health system and national tumor registries to identify patients diagnosed with adenocarcinoma of the colon or rectum from 2010-2014 at 6 US integrated health systems in the Patient Outcomes To Advance Learning (PORTAL) network. Tumor registry data included: age at diagnosis, stage, grade, anatomic site, histology, number of lymph nodes examined, and receipt of initial systemic therapy (chemotherapy or immunotherapy). Demographics and other patient characteristics were obtained from the EHR. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset ( &lt; 50 years old) vs. normal/late-onset CRC. Results: There were 1,424 early-onset and 10,810 normal/late onset CRC cases in our analyses. Compared to normal/late onset cases, patients with early-onset CRC were more likely to be Hispanic, obese, never smokers, and to have Charlson comorbidity scores &lt; 3. After adjustment for patient characteristics, compared to normal/late onset CRC, early-onset CRC was associated with more advanced stage disease (OR for stage 4 vs. stage 1 = 2.8, CI: 2.4-3.4), high grade histology (OR for poorly differentiated/undifferentiated vs. well/moderately differentiated = 1.2, CI: 1.1-1.5), signet ring histology (OR for signet ring vs. non-mucinous adenocarcinoma = 1.7, CI: 1.1, 2.6), and rectal (OR for rectum vs. cecum = 2.4, CI: 1.9-2.9) or left colon location (OR for left colon vs. cecum = 2.2, CI: 1.8-2.8). After adjustment for patient and tumor characteristics, early-onset patients were more likely than normal/late onset patients to have &gt; 12 lymph nodes examined (OR = 1.6, CI: 1.4-1.8) and to receive systemic therapy (OR = 2.8, CI: 2.4, 3.4). Conclusions: Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use.
Integrating Medical and Nonmedical Services — The Promise and Pitfalls of the CHRONIC Care Act
Authors: Amber Willink, Eva H. DuGoff
Journal: New England Journal of Medicine (2018)

Interview with Dr. Amber Willink on a new law that increases the flexibility of benefit offerings in Medicare Advantage plans. (11:32)Download The CHRONIC Care Act boosts efforts to provide more integrated care for Medicare beneficiaries to better address needs that are not strictly medical, but it may also substantially affect risk selection in Medicare Advantage plans, which would be counterproductive.
PTU-028 Adequate bowel preparation in small bowel capsule endoscopy: has it been a clearer future?
Authors: J Yin Liu, M Nanda Kumar, SM Ng, M Wong, A McNair, L Pee
Journal: Gut (2017)

Introduction  Capsule endoscopy (CE) relies on adequate bowel preparation to ensure good luminal views. Studies have given variable results on the efficacy of bowel preparation 1,2 . Our department moved from a regimen of 24 hour of clear fluids only (NP) to 24 hour of clear fluids and the addition of one sachet of polyethylene glycol (PEG1) after a retrospective audit of results 3 . As our results indicated PEG1 improved lesion detection compared to NP, we changed preparation to 24 hour of clear fluid combined with 2 sachets of PEG (PEG2). We present a retrospective look at our findings.  Method  Patients who underwent CE from January 2016 till July 2016 were identified via Rapid capsule endoscopy software. Data collected included indication for test, total lesions detected (TL) and lesions excluding aphthous ulcers (EL). 3 independent assessors reviewed images at 20 min intervals to determine adequacy of bowel preparation. Overall adequacy was determined by majority opinion. Data from our previous analysis using the same methods was added and data comparison of lesion detection in each arm was compared by Fisher’s test chi squared analysis.  Results  A total of 31 patients were identified in this timeframe but only 30 patients were included due to failure of one procedure. All patients received PEG2. Our results are shown in figure 1.  The only result which showed statistical significance was between PEG1 and PEG2 when comparing all lesions identified (p=0.045) although it appears that PEG1 was better than PEG2; and that PEG2 detected less lesions overall than NP. However, when normal examinations were discounted from all three arms and the subsequent results compared, there were statistically significant results between NP(36%) and PEG2(70%) showing PEG2 was better at detecting significant lesions.(x 2  5.790,p=0.0161).  Conclusion  In our study, it appears that bowel preparation with PEG is better than NP in detecting significant lesions, but that PEG2 is inferior to PEG1. This goes against recent larger scale prospective studies 4,5  which suggest that clear fluid preparation is not inferior to full bowel preparation; and it is unusual that half dose preparation seems more effective than full dose. However, our numbers are small and it is a retrospective analysis. Additionally, in our dataset, there were more normal studies in the PEG2 arm than the other two, which may have skewed results. Further large scale prospective studies need to be carried out to clarify this difficult question.  References  . Nivet al. World J Gastroenterol.2013Feb 28;19(8):1264–70.  . Rosaet al. World J Gastrointest Endosc.2013Feb 16;5(2):67–73.  . Omeret al. Poster - United European Gastroenterology Week,Barcelona 2015 Oct.  . Hookey  et al . Gastrointest Endosc.2017Jan;85(1):187–193.  . Kleinet al. Ann Gastroenterol.2016Apr-Jun;29(2):196–200.  Disclosure of Interest  None Declared
68Ga-PSMA PET/MR–Positive, Histopathology-Proven Prostate Cancer in a Patient With Negative Multiparametric Prostate MRI
Authors: Urs J. Muehlematter, Niels J. Rupp, Julian Mueller, Daniel Eberli, Irene A. Burger
Journal: Clinical Nuclear Medicine (2018)

Abstract Multiparametric MRI incorporating T2-weighted, diffusion-weighted, and dynamic contrast material–enhanced sequences is currently used for detection and localization of clinically important prostate cancer (PCa). The 68 Ga-labeled PET tracer targeting the prostate-specific membrane antigen (PSMA, 68 Ga-PSMA-11) is a promising diagnostic approach for staging and restating PCa. Recent studies suggest that 68 Ga-PSMA could also be used for primary PCa detection and localization. We report a case of a 68 Ga-PSMA PET/MR-positive lesion of the peripheral zone in a 73-year-old man with a negative preceding multiparametric MRI. Radical prostatectomy and subsequent histopathologic examination confirmed a Gleason 4 + 4 PCa.
Temozolomide and irinotecan (TEMIRI regimen) as salvage treatment of irinotecan-sensitive advanced colorectal cancer patients bearing MGMT methylation
Authors: F. Morano, S. Corallo, M. Niger, L. Barault, M. Milione, R. Berenato, R. Moretto, G. Randon, M. Antista, A. Belfiore, A. Raimondi, F. Nichetti, A. Martinetti, L. Battaglia, F. Perrone, G. Pruneri, A. Falcone, M. Di Bartolomeo, F. de Braud, F. Di Nicolantonio, C. Cremolini, F. Pietrantonio
Journal: Annals of Oncology (2018)

Non-randomized studies showed that temozolomide (TMZ) achieves an average 10% response rate in heavily pretreated metastatic colorectal cancer (mCRC) patients with promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). In this phase II trial, irinotecan and temozolomide (TEMIRI) combination regimen was assessed in irinotecan-sensitive, MGMT methylated/microsatellite stable (MSS) pretreated mCRC patients.Key inclusion criteria were centrally confirmed MGMT methylation by methylation-specific PCR, MSS mCRC, progression after at least two prior chemotherapy regimens for advanced disease and irinotecan-free interval >3 months. TEMIRI (TMZ 150 mg/m2 on days 1-5 plus irinotecan 100 mg/m2 on days 1, 15 q28 days) was administered for six cycles, followed by maintenance with TMZ. The primary end point was overall response rate (ORR). Exploratory translational analyses included MGMT immunohistochemistry (IHC) and methyl-BEAMing (MB).Between December 2014 and June 2017, 25 patients were enrolled. The primary end point was met, since six patients achieved a partial response [ORR 24%, 95% confidence interval (CI) 11% to 43%]. At a median follow-up of 15.6 months, median progression-free survival (mPFS) and overall survival (mOS) were 4.4 and 13.8 months, respectively. Only four (16%) patients had ≥ grade 3 (CTCAE 4.0) adverse events. All patients whose cancer was MGMT-positive IHC were non-responders. Consistently, patients with MGMT-negative/low tumors had a significantly longer mPFS than others (6.9 versus 2.0 months; hazard ratio = 0.29, 95% CI 0.02-0.41; P = 0.003) and a non-significant trend for longer mOS. MB testing showed similar accuracy.TEMIRI regimen is a safe and active option in pre-treated, irinotecan-sensitive mCRC patients with MGMT methylation.
Early stage in triple negative breast cancer: Breast conservative surgery versus mastectomy.
Authors: Gabriel Antonio De la Cruz Ku, Zaida Morante, Sofia Lizandro, Daniel Enriquez, Bryan Valcárcel, Renato Luque, Maria Luján, Eduardo Eyzaguirre, Antonella Saavedra, Cesar Razuri, Joseph Pinto, Jhajaira M Araujo, Hugo Alejandro Fuentes, Mecker Geraldine Moller, Danny Yakoub, Silvia P. Neciosup, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2018)

e12619 Background: The World Health Organization approved the breast-conserving surgery (BCS) in 1969. In spite of the aggressiveness of triple negative breast cancer (TNBC), BCS has demonstrated to be a promising alternative to mastectomy. In that way, we conducted 9 years of follow up of peruvian women with Stage (S) I-IIA of triple negative breast cancer (TNBC) to compare the surgical role and the relapse frequency among TNBC patients. Methods: We conducted a retrospective study among 540 patients diagnosed of TNBC with Stage (S) I-IIA at Instituto Nacional de Enfermedades Neoplasicas between 2000-2014. From all population, 486 underwent to surgery as first treatment. Characteristics were described by surgical technique: conservative or mastectomy. Differences in disease free survival (DFS) and overall survival (OS) were assessed by Log-rank test. Prognostic factors were obtained by Cox Regression analysis. Results: From 486 patients with surgical treatment, the median age was 50 years (21-86), 41.7% were premenopausal and 27.6% presented obesity. A total of 228 underwent conservative surgery and 258 had mastectomy. The mostly of young patients (54.8% vs 43.5%, p = 0.015) and who had a lower stage (39% vs 16.3%, p < 0.001) had BCS in comparison to mastectomy. However, also positive margins (44.1% vs 3.4%, p < 0.001) and extracapsular extension (4.8% vs 1.2%, p = 0.026) were more frequent in this group, as the same as radiotherapy (72.8% vs 23.3%, p < 0.001) and the use of anthracyclines + taxanes in chemotherapy (CT) (67.1% vs 42.1%, p < 0.001). At 5-year, rates of DFS (76% vs 79%, p = 0.35) and OS (90% vs 87%, p = 0.46) were similar among both groups. In the univariate analysis, just CT showed a benefit on DFS and OS. At multivariate analysis, just CT (HR:0.51, 95%CI: 0.33-0.81, p = 0.004) demonstrated a positive impact on DFS. Conclusions: BCS has demonstrated similar rates of DFS and OS than mastectomy, however it has better survival rates. In spite of the benefit of RT for BCS, chemotherapy is essential among these patients.
Real world evaluation of effectiveness and tolerance of chemotherapy for early stage breast cancer (ESBC) in elderly women.
Authors: Glenda Maria Delgado Ramos, Syed Sameer Nasir, Jiajing Wang, Vikki G Nolan, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2018)

e12509 Background: While elderly patients (pts) diagnosed with ESBC represent a substantial fraction, they tend to receive less aggressive treatment, have higher mortality rates and are markedly underrepresented in clinical trials. We sought to assess the tolerance and effectiveness of chemotherapy in this population. Methods: We retrospectively reviewed consecutive elderly pts (≥ 70 years) with ESBC receiving neo/adjuvant chemotherapy at West Cancer Center, Memphis, TN, from Jan/2010 to Dec/2016. Data was obtained by chart review. Primary end-points included overall survival (OS) and disease-free survival (DFS), assessed by Kaplan-Meier method. Associations with early chemotherapy cessation and severe toxicity were also sought. Results: From 937 elderly pts with ESBC, 229 received chemotherapy [Table 1]; 77% completed all planned cycles; 21% had dose reduction and 30% had dose delays. Most common regimens were taxane combinations and CMF, with 85% and 75% respectively completing these. Severe, very severe and lethal toxicities occurred in 42%, 1.2% and 0.5% of the pts, respectively. Fatigue (32%) and hematological (23%) toxicities were most common. 70 emergency room visits occurred; 54 of them required hospital admission. 1- and 3-year OS were 95% and 79%, respectively; and 1- and 3-year DFS were 93% and 80%, respectively. Increased comorbidities (p = 0.02) and older age (p = 0.003) were associated with chemotherapy cessation. No significant associations with risk of severe toxicity was observed, however, a trend was noted with older age (p = 0.11) and increased comorbidities (p = 0.11). Conclusions: Chemotherapy can be effectively delivered to elderly women with ESBC and was overall reasonably well tolerated. A substantial proportion required hospital services. Long-term outcome demonstrates high-risk nature of pts selected for treatment. Older age and increased comorbidities predicted chemotherapy cessation, and possibly toxicity. Table 1. Patients’ characteristics. N = 229; [n, %] Age, y (range) 74 (70, 91) Follow-up, m (IQR) 30 (15, 53) ECOG PS (missing in 30%) 0 - 1 147 64% 2 - 3 12 5% Tumor Markers ER/PR + 82 36% HER2 + 60 26% ER/PR/HER2 - 87 38% Stage at diagnosis I 58 25% II 104 46% III 66 29%
Race and social status related to different health behaviors in breast cancer patients.
Authors: Kezhen Fei, Rebeca Franco, Veluswamy Rajwanth, Nina A. Bickell
Journal: Journal of Clinical Oncology (2018)

e12528 Background: Perceived socioeconomic status (SES) may be an important social determinant of health, cancer risks, access to care and health outcomes. We conducted this study to assess the relationship between breast cancer patients’ perceived socioeconomic positions with their health behaviors and cancer prognosis. Methods: Data were collected as part of a large prospective study evaluating the role of insulin resistance in women diagnosed with new breast cancers. Patients were presented a ten rung ladder (McArthur scale), and were asked to subjectively place themselves according to their standing in their communities. Patients were grouped as perceived low status (rung 1-8) or high status (rung 9-10). Additional questions assessing objective SES measures, health and cancer screening behaviors were included. We used Nottingham Prognostic Indicator (NPI) to measure cancer prognosis ( > 4.4 = poor prognosis). Results: Of 810 patients with average age of 58 years old, 83% were white and 17% black. 80% reported low status and 20% high status. Overall, 24% of black and 19% of white women reported high social status (p = 0.2). 74% vs 62% of the high perceived status group graduated college (p = 0.02). Several racial differences were noted: higher rates of college education (70% vs 37%; p < .0001), income ≥$75,000 (66% vs 24%; p < .0001), commercial insurance (90% vs 82%; p = 0.01), heavy alcohol (31% vs 9%; p < .0001), and healthy diet (57% vs 29%; p < .0001) among whites; and higher rates of never smokers (72% vs 53%; p = 0.0003), no physical activity (57% vs 46%; p = 0.02) and poor prognosis (29% vs 16%; p = 0.0002) among blacks. However, no racial disparity was observed in cancer screening (i.e., mammography, colonoscopy, Pap smears). Patients with high perceived social status were more likely to have a healthier diet (70% vs 49%; p < .0001) and to have mammograms within 2 years (88% vs 77%; p = 0.003; aOR = 2.47; 95% CI: 1.41-4.32), but no differences in Pap smear or colonoscopy within designated times. Conclusions: Race and perceived SES appear to relate to different health behaviors. While race is related to key social determinants of health and cancer prognosis, perceived SES may provide information about screening behaviors.