tbuckley/cabot-search huggingface dataset:
Outcomes of patients with relapsed/refractory diffuse large B-cell lymphoma treated with R-ICE based on dual expression of <i>MYC</i> and <i>BCL2.</i>
Authors: Joshua M. Allen, Ana Lucia Ruano Mendez, Lisa A. Rybicki, Deepa Jagadeesh, Robert M. Dean, Brad L. Pohlman, Mitchell Reed Smith, Eric D. Hsi, Brian Thomas Hill
Journal: Journal of Clinical Oncology (2016)

e19043 Background: Diffuse large B-cell lymphoma (DLBCL) with dual expression (DE) of MYC and BCL2 has poorer prognosis than non-DE following 1st line R-CHOP. Recent data show relapsed/refractory (r/r) DE DLBCL also has inferior outcomes after high-dose chemotherapy (CTX) and autologous stem cell transplantation (ASCT). [Herrera, et al, ASH 2015] Only 50-60% of r/r patients (pts) who receive 2nd line CTX such as R-ICE proceed to ASCT. We studied outcomes of r/r pts treated with R-ICE and intent to transplant to determine the prognostic effect of DE. Methods: We reviewed charts of 167 consecutive de novo or transformed DLBCL pts with adequate clinical follow-up treated with 1st line R-CHOP/R-EPOCH and salvage R-ICE from 2000 to 2015. Pts were grouped as DE (N = 26) and non-DE (N = 141). Predefined cutoffs for positivity by immunohistochemistry at relapse were ≥ 50% for MYC (N = 34) and ≥ 40% for BCL2 (N = 101). DLBCL was classified as germinal center B-cell (GC) or non-GC using Hans algorithm. Clinical characteristics were compared by Chi-square, Cochran-Mantel-Haenszel, t- or Wilcoxon tests. ASCT outcome was estimated by the cumulative incidence method and compared by the Gray test. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the log-rank test. Prognostic factors for OS were assessed by Cox proportional hazards analysis. Results: DE pts were older (mean age 63 years vs. 56 years, P = 0.009) and were less likely to be GC (44% vs. 69%, P = 0.018). 66% had ASCT, with no difference between DE (14/26) and non-DE (97/141). 5-year OS of DE pts was 26% versus 54% for non-DE (P = 0.03). There was no difference in OS between pts with or without overexpression of BCL2 or MYC in the absence of DE. In multivariable analysis, DE was associated with higher mortality risk (HR 2.23, 95% CI 1.18-4.21, P = 0.013). Conclusions: DE pts have poorer OS than non-DE pts in the 2nd line setting when treated with R-ICE and intent for ASCT. Given the enrichment of r/r pts with BCL2 overexpression, these data provide rationale for clinical trials investigating the addition of targeted molecular therapies to R-ICE, such as the BCL2 inhibitor venetoclax, for r/r DLBCL pts who relapse after initial R-CHOP.
Feasibility trial of collecting patient-generated health data using a wearable device and electronic patient-reported outcomes in cancer patients.
Authors: Tempei Miyaji, Takashi Kawaguchi, Kanako Azuma, Shinya Suzuki, Yoko Sano, Moe Akatsu, Ayako Torii, Tadamasa Kamimura, Yuki Ozawa, Akihiko Tsuchida, Daisuke Eriguchi, Mizuha Haraguchi, Makoto Nishino, Yoshiki Tokuda, Yoshiko Nishi, Motohide Nishi, Rintaro Takeya, Yumi Inadome, Tsutomu Yamazaki, Takuhiro Yamaguchi
Journal: Journal of Clinical Oncology (2018)

e18725 Background: Patient-generated health data (PGHD) from electronic mobile devices provide new methods to monitor daily physical activities and functioning of cancer patients both in clinical research and general practice. In order to utilize PGHD in clinical oncology research, the feasibility of using these devices needs to be further investigated. This pilot trial aimed to investigate the feasibility of using a wearable device in cancer patients in a clinical research setting. The correlation between PGHD and patient-reported outcomes regarding major cancer symptoms was also explored. Methods: Adult patients with any cancer who were planning to receive first-line systemic chemotherapy, able to use their own smartphone, and admitted to hospital at the time of enrollment were eligible. Patients were asked to wear a wristband-style device (Garmin Vivofit 3®) for 28 days from the day before the initiation of chemotherapy. The primary endpoint was adherence to wearing the device. “Well-adhered” patients were defined as those who wore the device for more than 70% of the time over the 28-day period. Feasibility was defined as more than 70% of patients being “well-adhered.” Major secondary endpoints were Brief Fatigue Inventory (BFI), MD Anderson Symptom Inventory (MDASI), Pittsburgh Sleep Quality Index (PSQI), and NCI CTCAE v4. Results: A total of 30 patients enrolled from July to November 2017. Participants had a mean age of 58.6 years, and 21 (70%) were male. Further, 15 (50%) had gastrointestinal cancer, and 11 (36.7%) had lung cancer. Of the 30 patients, 27 (90%, 95% CI: 0.73-0.98) were well adhered to the device for 28 days and met the primary endpoint. The mean adherence was 85% (95% CI: 0.80-0.90). The adherence correlated with the frequency of synchronization of the device (r = 0.62). The degree of physical activity fairly correlated with the baseline scores of BFI global fatigue score (r = -0.38) and MDASI core symptom severity score (r = -0.40). Conclusions: The feasibility of using a wearable device was confirmed in cancer patients receiving chemotherapy. To implement these technologies in clinical trials, we should further optimize the process of data collection. Clinical trial information: UMIN000027575.
P01.072 Hydroxychloroquine and short course radiotherapy for elderly patients with glioma: a randomised study
Authors: L Brazil, A Swampillai, K Mak, A Hackshaw, D Edwards, P Mesiri, L Clifton-Hadley, R Shaffer, J Lewis, C Watts, P Gkogkou, A Chalmers, N Fersht, S C Short
Journal: Neuro-Oncology (2018)

Treating elderly patients with glioblastoma remains challenging and alternatives to conventional cytotoxics, particularly in patients with unmethylated tumours are required. Pre-clinical data suggest that autophagy inhibition sensitizes gliomas to radiotherapy and chemotherapy We conducted an open-label multicentre randomized phase-II study of patients aged >=70, performance status 0–1 with newly diagnosed high-grade glioma considered suitable for short course radiotherapy. They were randomized (1:2) to a calibration arm given radiotherapy (RT) alone (30Gy;5Gy/6fractions over 2 weeks), or an experimental arm given RT plus hydroxychloroquine (HCQ, 200mg orally twice daily) from 7 days prior to RT until progression/toxicity. The primary endpoint was one-year overall survival (OS; target 34%). Secondary endpoints included progression free survival (PFS), quality of life and toxicity. Fifty-three patients with median age 75 were included May 2013 to Oct 2016 (n=35 RT+HCQ, n=18 RT alone). One-year survival was 20.3% (95%CI 8–36) in the experimental arm and median OS was 7.9 months. In the calibration arm, one-year survival was 47.6% (95%CI 2–71) and median OS was 11.8 months. Six-month PFS was 25.2% vs 36.5%. Grade 3–5 toxicities occurred in 60% (RT+HCQ) and 38.8% (RT alone), which was not significantly different, with no obvious imbalance in specific events. Common toxicities included lethargy and pulmonary infections. QoL did not differ between arms. The Data Monitoring Committee stopped recruitment early because the experimental arm could not reach its target 1-year OS Despite growing interest in autophagy inhibition as a potential mechanism for treating cancer, giving HCQ with short course radiotherapy did not improve outcomes compared to radiotherapy alone. Although median OS was similar to data from other studies for this patient group, it was worse than the calibration arm. Future opportunities could include using higher doses of HCQ, or definition of selective biomarkers for response to autophagy inhibition.
Impact of adjuvant FOLFOX on quality of life and peripheral neuropathy incidence in patients with localized gastric cancer.
Authors: Sebastián Mondaca, Juan Briones, Nicole Caire, Jose Pena, Bruno Nervi, Enrique Norero, Marcelo Garrido
Journal: Journal of Clinical Oncology (2018)

e16039 Background: In localized gastric cancer there is evidence supporting a survival benefit for perioperative chemotherapy, adjuvant chemotherapy and adjuvant chemoradiotherapy. However, there is limited data about impact on quality of life (QoL) of these strategies. We prospectively assessed QoL and chemotherapy induced peripheral neuropathy (CIPN) in a cohort of patients treated with adjuvant FOLFOX chemotherapy. Methods: We recruited patients with histological diagnosis of gastric or gastroesophageal junction adenocarcinoma that underwent curative resection and were considered candidates for adjuvant FOLFOX for 12 cycles. To assess QoL we used the EORTC C30 questionnaire and for CIPN we used EORTC CIPN20 questionnaire. Patients completed these questionnaires before cycles 1, 3, 5, 7, 9 and 11, and 4, 12 and 24 weeks after the last cycle. We considered clinically significant deterioration of QoL evaluated as a time to event outcome and in a linear mixed model analysis as co-primary outcomes. This event was defined as a drop of 10 or more points of the sub scale global health status of the EORTC C30 questionnaire. Results: We recruited 64 patients during the study period. The median age in this cohort was 62.5 years and the stomach was the most frequent tumor location (67%). At 24 weeks after starting treatment 29% of patients did not develop clinically significant deterioration of QoL and 7% did not have clinically significant CIPN. The least square mean change from baseline to 4 weeks after completing adjuvant chemotherapy for global health status and sensory scale was -7.6 (95% CI, -13.5 to -1.9) and 21.9 (95% CI, 17.3 to 26.6) respectively. From the start of adjuvant chemotherapy to the end of treatment and 6 months thereafter the mean weight loss was 3.1 Kg (p < 0.001) and 1.1 Kg (p = 0.27) respectively. With a median follow up of 21.6 months the 2-year disease free survival and 2-year overall survival were 78% and 84% respectively. Conclusions: Adjuvant FOLFOX is associated with a significant deterioration in QoL and high incidence of CIPN in patients with localized gastric cancer. A perioperative approach should be favored in this setting. Clinical trial information: NCT02577263.
The Geriatric-Oncologic Conference: A new approach in decision-making.
Authors: Sebastian Willy Ertl, Hans-Christoph Heuer, Michael Stahl
Journal: Journal of Clinical Oncology (2016)

e18222 Background: A comprehensive geriatric assessment (CGA) is recommended before treating elderly cancer patients. However, it is not proven that additional information from the CGA will change our treatment decision. Methods: 421 cancer patients, 65 years or older, were judged by their treating oncologist regarding fitness for chemotherapy. Accompanying a CGA was performed and each patient was discussed in a multidisciplinary board (MB) including a geriatrician. The differences between the judgement of the treating oncologist, the MB, and a classification based solely on the CGA were examined. Additionally a statistical model of the decision making process within the MB, based on the findings of the CGA was established and evaluated. Results: Treating oncologist and MB judged 12% and 15% of the patients as frail, 41% and 38% as vulnerable, 46% and 47% as fit. 83% of congruence was observed. Based on the proposal of Balducci, 55% of the patients were classified as frail, 30% as vulnerable and 15% as fit. 34% of congruence with treating oncologist judgement was observed. In the 2-stage logistic model the activities of daily living and the mini mental state examination (MMSE) discriminated between frail and vulnerable or fit. Tinetti test, age, Charlson comorbidity index, living alone, MMSE and mini nutritional assessment discriminated between vulnerable and fit. The statistical models were able to differentiate with an accuracy of 95% between frail and vulnerable or fit and 83% between vulnerable and fit. Conclusions: To our experience, the judgement of an experienced oncologist is well comparable with the judgement of a MB. Nevertheless, for some patients discussion of CGA data in the MB may essentially change treatment decisions. A logistic regression model of the decision making process within the MB may replace the elaborate team discussion, if a conference is not feasible.
Abstract 20256: Exposure to Heavy Metals Linked to Increased Left Ventricular Mass and Abnormal Geometry
Authors: Jacqueline O’Boyle, Rupa L Iyengar, Anoop Sahota, Cynara Maceda, Christina Wyatt, Mary Ann McLaughlin
Journal: Circulation (2016)

Introduction: First Responders working at Ground Zero following the 9/11 tragedy were exposed to particulate matter including heavy metals. Heavy metals such as cadmium (Cd) and lead (Pb) are not readily excreted by the body and elevated levels have been noted post exposure. Cadmium exposure has been associated with increased risk of stroke, heart failure, and cardiovascular mortality. Lead exposure is known to affect cardiac function. Given the high levels of exposure to particulate matter at Ground Zero this study seeks to evaluate the cardiac morphology of First Responders with elevated blood and urine levels of Cd and Pb. Methods: We evaluated 347 enrolled first responders from the World Trade Center-RENAL Program. Participants received a complete echo Doppler study. LV geometry was determined by relative wall thickness (RWT) and LV mass index (LVmi). Concentric hypertrophy was defined as elevated RWT and LVmi, eccentric hypertrophy defined by elevated LVmi with normal RWT and concentric remodelling d...
P05.32 Update on a metronomic antiangiogenic combination therapy for recurrent atypical teratoid rhabdoid tumor
Authors: I Slavc, A Peyrl, M Chocholous, T Czech, K Dieckmann, C Haberler
Journal: Neuro-Oncology (2018)

Prognosis of patients with recurrent atypical teratoid rhabdoid tumor (ATRT) is dismal despite intensive therapy including high-dose chemotherapy with stem cell rescue. An evolving alternative approach to conventional chemotherapy is to target neovascularisation by interfering with tumor angiogenesis at various levels. We report on 12 patients with recurrent ATRT treated with an antiangiogenic combination therapy. Patients and Methods: From 03/2008 to 02/2018, 12 patients were diagnosed with recurrent ATRT (6 first, 6 multiple recurrences), three had germ line mutations. Treatment consisted of an antiangiogenic multidrug-regime including IV bevacizumab, oral thalidomide, celecoxib, fenofibrate, and etoposide alternating with cyclophosphamide, and augmented with intraventricular therapy (etoposide and liposomal cytarabine) with or without focal radiotherapy. Median age at start of antiangiogenic therapy was 3 (1–12) years. As of 05/2018, 6/12 patients are alive and in CR for 123, 90, 45, 9, 6 and 3 months after start of antiangiogenic therapy, the first three off therapy. One patient died of another cause 50 months after her recurrence in CR and without evidence of tumor at autopsy. OS for the whole cohort was 47.7 ± 16.6% at 3 years and 31.8 ± 17.1% at 5-years with a median OS of 22.8 months (KI 0.0–66.8). Therapy was generally well tolerated and toxicities were manageable. The proposed antiangiogenic regimen is currently being evaluated for medulloblastomas in an international phase II protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290). The same approach seems to be also efficacious in recurrent ATRTs and warrants further evaluation.
Epidemiological profile and factors associated with mortality among women with gynecological cancers in a Haitian cancer program.
Authors: Joseph Bernard, Vincent DeGennaro
Journal: Journal of Clinical Oncology (2018)

e13607 Background: Gynecological cancers are among the main cancers affecting women worldwide, especially in low and middle-income countries. Their epidemiology in Haiti is to date poorly known. This study aimed to describe the epidemiology of gynecological cancers in Haiti and determine factors associated with mortality. Methods: A two-year retrospective study was conducted in the cancer program of Innovating Health International (IHI), in Port-au-Prince, Haiti. A chart review including women diagnosed from January 1st, 2016 to December 31st, 2017 collected data on key variables such as age, cancer type, International Federation of Gynecology and Obstetrics (FIGO) classification, baseline performance status, obstetrical background and outcome. These variables were then evaluated as possible factors associated with mortality. Results: One hundred and thirty-eight (138) cases of gynecological cancers were diagnosed during the study period. Gynecological cancers are the second most common malignancies in our cohort after breast cancer. The median age was 54 years [27-90]. 9.4% of the patients admitted tobacco use. 57.2% of the women were postmenopausal and 23.2% reported use of hormonal contraception. 28.2% of the patients had a history of abortion. Cervical cancer was the most common cancer type with 71.7% of the cases, followed by ovarian cancer (15.2%), endometrial cancer (11.6%), vulvar cancer and choriocarcinoma with 0.7% of the cases each. 72.1% of the patients with FIGO classification were at stages III or IV. The overall mortality rate was 31.9%, and 10.9% of the patients were lost to follow-up. Patients were more likely to die if they had ovarian or uterine cancer (Odds Ratio (OR) = 2.7, p = 0.01), were at stages III or IV (OR = 10, p = 0.0005) or had a baseline ECOG ≥ 1 (OR = 8.9, p = 0.00001). Conclusions: Gynecological cancers are diagnosed at a late stage in Haiti, which has an impact on treatment options and survival. Awareness and screening programs need to be reinforced in Haiti to insure earlier diagnosis and patient retention, especially for cervical cancer. A national anti-HPV vaccination program is mandatory to decrease the burden of cervical cancer in Haiti.
Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids
Authors: Sarah J. Hill, Brennan Decker, Emma A. Roberts, Neil S. Horowitz, Michael G. Muto, Michael J. Worley, Colleen M. Feltmate, Marisa R. Nucci, Elizabeth M. Swisher, Huy Nguyen, Chunyu Yang, Ryuji Morizane, Bose S. Kochupurakkal, Khanh T. Do, Panagiotis A. Konstantinopoulos, Joyce F. Liu, Joseph V. Bonventre, Ursula A. Matulonis, Geoffrey I. Shapiro, Ross S. Berkowitz, Christopher P. Crum, Alan D. D'Andrea
Journal: Cancer Discovery (2018)

Abstract Based on genomic analysis, 50% of high-grade serous ovarian cancers (HGSC) are predicted to have DNA repair defects. Whether this substantial subset of HGSCs actually have functional repair defects remains unknown. Here, we devise a platform for functional profiling of DNA repair in short-term patient-derived HGSC organoids. We tested 33 organoid cultures derived from 22 patients with HGSC for defects in homologous recombination (HR) and replication fork protection. Regardless of DNA repair gene mutational status, a functional defect in HR in the organoids correlated with PARP inhibitor sensitivity. A functional defect in replication fork protection correlated with carboplatin and CHK1 and ATR inhibitor sensitivity. Our results indicate that a combination of genomic analysis and functional testing of organoids allows for the identification of targetable DNA damage repair defects. Larger numbers of patient-derived organoids must be analyzed to determine whether these assays can reproducibly predict patient response in the clinic. Significance: Patient-derived ovarian tumor organoids grow rapidly and match the tumors from which they are derived, both genetically and functionally. These organoids can be used for DNA repair profiling and therapeutic sensitivity testing and provide a rapid means of assessing targetable defects in the parent tumor, offering more suitable treatment options. Cancer Discov; 8(11); 1404–21. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1333
Doctors question Hancock’s idea of GP video consultations for all
Authors: Adrian O’Dowd
Journal: BMJ (2018)

The government’s call for GPs in England to offer all patients smartphone video consultations have been met with scepticism from doctors’ leaders and health experts.

In an interview with the Telegraph newspaper published on 12 September, the health and social care secretary, Matt Hancock, said that he wanted to see a system in which all patients could use their smartphone, tablet, or computer to have Skype-like video consultations with their GP.1

Hancock has admitted that he uses the GP at Hand app provided by Babylon Healthcare. The service, which is offered by the NHS in some parts of London, enables patients to have video consultations with a doctor or to arrange a face-to-face …
Changing patterns of metastatic pancreatic cancer (mPC) care in the combination therapy era: A geriatric perspective.
Authors: Rishi Jain, Namrata Vijayvergia, Karthik Devarajan, Raji Shameem, Bianca Lewis, Crystal Shereen Denlinger, Steven J. Cohen, Efrat Dotan
Journal: Journal of Clinical Oncology (2016)

10048 Background: Front-line treatment strategies in mPC have evolved since the FOLFIRINOX data presentation at ASCO 2010 (Conroy et al.) showed improved outcomes with a combination chemotherapy regimen over single agent gemcitabine. We compared patterns of care and outcomes of older mPC patients before and after 2010 at an academic cancer center. Methods: A retrospective analysis of medical charts of older (age ≥ 65) mPC patients treated between 2000-2009 (group 1, n = 280) or 2010-2015 (group 2, n = 193) was performed. Groups were compared by gender, performance status, diagnosis stage, type and number of chemotherapeutic agents received, and overall survival (OS) after diagnosis of mPC. Log-rank tests were used to analyze survival endpoints and Fisher’s exact test was used to compare categorical variables. Results: The groups were well balanced with respect to age (median 73), gender and diagnosis stage (majority IV). Chemotherapeutic agents used in each group are summarized in table 1. Overall, patients in group 2 were more likely to receive any chemotherapy for mPC (81% vs 66%, p < 0.005). 57% of patients in group 2 received combination regimens in the first line setting. There was increased use of fluoropyrimidines, platinum, irinotecan and taxanes in group 2. There was no significant difference in the use of gemcitabine or erlotinib between groups. Patients in group 2 had improved median OS (6 months vs 5 months, p < 0.005). Conclusions: Older mPC patients treated after 2010 were more likely to receive multiple chemotherapeutic agents compared to older patients treated prior to 2010. These interventions were associated with a small survival advantage. Although these results are in line with the standard of care, the small OS advantage and significant toxicity profile of these treatments warrant further research to optimize the treatment of older mPC patients. Group 1 N (%) Group 2 N (%) p value # Pts 280 193 Gemcitabine 207 (74) 139 (72) = 0.330 Fluoropyrimidine 74 (26) 108 (56) < 0.005 Platinum 30 (11) 93 (48) < 0.005 Taxane 10 (4) 49 (25) < 0.005 Irinotecan 4 (1) 44 (23) < 0.005 EGFR inhibitor 44 (16) 19 (10) = 0.054 > 1 Agent 105 (37) 132 (68) < 0.005 Median # Agents 1 2 < 0.005 OS 5 months 6 months < 0.005