tbuckley/cabot-search huggingface dataset:
Risk-reducing mastectomy rates in the US: A closer examination of the Angelina Jolie effect.
Authors: Alexander Liede, Mona Cai, Tamara Fidler Crouter, Daniela Niepel, Fiona Callaghan, D. Gareth Evans
Journal: Journal of Clinical Oncology (2018)

e13557 Background: On 14 May 2013, actress, filmmaker and humanitarian, Angelina Jolie, disclosed in an open New York Times editorial that she had undergone risk-reducing bilateral mastectomy (RRBM) after learning that she was a BRCA1 mutation carrier. Following the attention associated with the announcement, Time magazine coined the phrase the “Angelina Jolie Effect”, to describe the subsequent rise in internet searches related to breast cancer genetics and counseling. We examined the rates of BRCA testing and RRBM from 1997 through 2016, and quantified trends before and after the Jolie op-ed. Methods: This is an observational study of insurance claims data representative of the commercially-insured US population measuring BRCA testing and RRBM rates. Included were females 18 years and older with encounters in the Truven MarketScan® commercial insurance database since 1997. Administrative end of follow up was September 2016. Women were censored at the time of breast cancer or ovarian (including fallopian tube and peritoneal primary) cancer diagnosis, last date of follow up, or death. Interrupted time series analyses were used to quantify trends before and after 14 May 2013. Results: Angelina Jolie’s open editorial in the New York Times led to a measurable and statistically significant increase in the uptake of genetic testing and in RRBM among women without a previous diagnosis of breast or ovarian cancer in the US population, and in women who did not undergo testing for BRCA (P < 0.0001 for both). The editorial did not have an impact on the rate (slope) of RRBM among women who were previously tested for BRCA (P= 0.70). When women with in-situ tumors were excluded, the effect of the editorial became less pronounced, suggesting that high-risk women with in-situ breast cancers were the most influenced by Jolie’s announcement. Conclusions: The Angelina Jolie Effect represents a long-lasting impact of celebrity on public health awareness as significant increases in genetic testing and mastectomy rates were observed and sustained in subsequent years.
Does the risk of emergency department visits and hospitalizations during systemic therapy for cancer influence patient decisions regarding treatment?
Authors: Monika K. Krzyzanowska, Cameron Phillips, Ken Deal, Melanie Lynn Powis, Simron Singh, Laavanya Dharmakulaseelan, Harsh Naik, Aditi Dobriyal, Nasrin Alavi
Journal: Journal of Clinical Oncology (2018)

213 Background: When different treatments (tx) produce similar prognostic outcomes, other tx attributes such as toxicity may impact tx preferences. We conducted a discrete choice experiment to evaluate how patients’ value the risk of an emergency department visit (ED) or hospitalization during treatment when deciding about chemotherapy. Methods: Patients with breast, head and neck or colorectal cancer who were contemplating, receiving or had previously received systemic treatment were recruited from 2 academic cancer centres in Toronto, Ontario. Each participant completed 10 choice tasks (5 each in the adjuvant and metastatic settings, respectively) from a possible 128 combinations. Each choice task prompted them to choose between two hypothetical systemic therapies, based on 3 attributes (likelihood of benefit, risk of requiring an ED visit and risk of hospitalization during treatment) that varied across 4 levels. Data was analyzed using a multinomial logit model and individual part-worth utility (PWU) values were estimated using hierarchal Bayes routines. Results: Between 06/2015 and 09/2017, 293 patients completed the survey. Most patients were female (76%), had a diagnosis of breast cancer (63%) and were currently receiving systemic therapy (72%). 59% of patients were receiving tx with curative intent. PWU values varied as expected with higher PWUs seen for higher treatment benefit, lower risk of ED visits and lower risk of hospitalization. Treatment benefit was the most important decision attribute in both the adjuvant (59%, 95%CI 57.8-60.1%) and metastatic (67.7%, 95%CI 66.8-68.7%) scenarios, followed by risk of hospitalization (18.8 vs 22.8%) then risk of ED visits (13.5 vs 18.3%). Results were the same when stratified by patient’s own treatment intent. Conclusions: While the risks of hospitalization and ED visits contribute to patient tx preferences, the extent of tx benefit was the most important attribute regardless of treatment intent.
Survival benefit of obesity in stage IV colorectal cancer: Better tolerability of chemotherapy?
Authors: Catherine G Tran, Elise E Hill, Braden Jensen, Austin C Stark, Meghan Flannery, Daniel James Berg, Carlos Hou Fai Chan
Journal: Journal of Clinical Oncology (2018)

e15629 Background: Obesity is a known risk factor for the development of colorectal cancer (CRC) and has long been associated with increased mortality of CRC. However, recent studies have shown that obesity is associated with improved cancer survival, a phenomenon termed "obesity paradox." The purpose of this study is to revisit the impact of obesity on survival of stage IV CRC. Methods: Retrospective analysis of CRC patients presenting to the Holden Comprehensive Cancer Center between January 2006 and April 2016 was conducted under an approved IRB protocol. Clinicopathological and follow-up data were prospectively gathered in the institution's cancer registry. Body mass index (BMI) at time of diagnosis and treatment details were obtained from patients' electronic medical records. Patients were grouped by BMI as normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25-30 kg/m2) and obese (OB, > 30 kg/m2). Continuous and categorical variables were analyzed using ANOVA and chi-square statistical methods, respectively. Survival probabilities of different study groups were estimated and plotted using the Kaplan-Meier method. Results: Records of 375 patients with stage IV CRC were obtained, including 126 NW, 129 OW, and 120 OB patients. With a median follow-up of 16.1 months, median overall survival (OS) was higher in OB than NW patients (20.7 vs. 15.7 months, P < 0.001). No difference in age, gender, race, primary tumor site, KRAS/BRAF mutational status, metastatic sites, and surgical treatment was found between study groups. Duration of chemotherapy was significantly longer for OB than NW patients (12.1 vs. 5.4 months, p = 0.006). Conclusions: OB patients have improved survival after diagnosis of stage IV CRC and longer duration of chemotherapy compared to NW patients. While the causal relationship would be difficult to establish, these results suggest OB patients may tolerate chemotherapy longer due to the presence of excessive nutritional reserve, leading to better survival.
Quality assurance for investigator-initiated trials.
Authors: Karen O. Allen, Mohamed El Shayeb, Mansoor N. Saleh, John B. Fiveash
Journal: Journal of Clinical Oncology (2016)

e18160 Background: The quality assurance program (QAP) at the UAB Comprehensive Cancer Center strives to ensure the safety of clinical trials subjects, accuracy of data, compliance to regulatory mandates, and protocol compliance for therapeutic and non-therapeutic investigator-initiated trials (IIT). We aimed to observe trends over the past four years and to explore improvements for deficiencies in subsequent audits. Methods: We reviewed audits between 2012 and 2015 and relevant audits prior to 2012. Audits were categorized into administrative (regulatory and consent form (ICF) review) or full (administrative and patient care review). Extracted data included audit date, number of deficiencies, and requirement for a corrective action/preventive action (CAPA) plan. We further categorized deficiencies as ICF, eligibility, IRB, source documentation, and missing lab/tumor assessments. Data from initial and subsequent audits for the same protocol was compared. A two-tiered analysis was performed. First, the number of deficiencies during each calendar year was calculated to identify trends. Second, we conducted univariate-analysis using paired t-test and the McNemar test to estimate reduction in the number of deficiencies. The analysis compared the first and second audits and the first and last audits, respectively. Results: A total of 145 audits (84 administrative, 61 full) on 56 protocols (32 non-therapeutic, 24 therapeutic) were analyzed. No trend of deficiencies was found across subsequent calendar years. The univariate-analysis showed ICF deficiencies as being the most frequent with a mean reduction of 7.5 (p < 0.01) and 8.3 (p = 0.02) comparing the first to second audits and the first to last audits, respectively. A significant decline of CAPAs from 37.5% to 12.5% and 37.5% to 9% (p < 0.01 and p = 0.01) was similarly observed. Conclusions: The lack of reduction in overall deficiencies may be attributed to new investigators and staff turnover highlighting the importance of ongoing training for research personnel. Despite the absence of a deficiency reduction across calendar years, we observed significant improvement in two key compliance categories, ICF and CAPA, indicating QAP is an important tool in the overall compliance and oversight of IITs.
Emerging genomic landscape and therapeutic targets in young patients with colorectal cancer (CRC).
Authors: Christopher Hanyoung Lieu, Erica Golemis, Jihye Kim, Ilya Serebriiskii, Mark Bailey, Aik-Choon Tan, Todd M. Pitts, Cathy Eng, Riley Ennis, S. Gail Eckhardt, Garrett Michael Frampton, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2016)

3589 Background: Patients younger than 50 years comprise roughly 10% of the total incidence of CRC, but the incidence in young patients is increasing. This study investigated genomic differences between younger and older CRC tumors to identify potential therapeutic targets for this patient population. Methods: DNA was extracted from formalin-fixed, paraffin-embedded sections from 4699 cases of colorectal cancer (4001 colon and 698 rectal). Comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a mean specimen median sequencing depth of 688X for all coding exons and selected introns of up to 403 cancer-related genes. Younger patients with CRC were defined as < 40 years and older patients with CRC were defined as ≥ 55 years. P values were calculated using Fisher’s exact test; false discovery rate (FDR) and 95% confidence intervals (95%CI) were also calculated. Results: Gene alteration rates in the younger and older cohorts were similar in a majority of the genes analyzed. In the colon cancer analysis, alterations in CTNNB1 (p < 0.001, FDR = 0.08) and MLH1 (p < 0.001, FDR = 0.03) were found to be more common in younger patients compared to older patients. Older patients were more likely to have alterations in APC (p < 0.01, FDR < 0.01) and FAM123B (p < 0.01, FDR = 0.03). In the combined colon and rectal analysis, CTNNB1 (p < 0.001, FDR = 0.07) and MLH1 (p < 0.001, FDR = 0.02) alterations were found to be more common in younger patients with CRC, and APC (p < 0.01, FDR < 0.01) was more commonly altered in older patients with CRC. When focusing on truncating mutations and deletions only, young rectal cancer patients were found to have a log ratio of 3.7 for lesions in FAM123B (p = 0.02, 95%CI: 0.08-0.96) compared to colon cancer. CTNNB1 was found to have a 1.5X rate of mutation in colon compared to rectal cancer, not reaching statistical significance. Conclusions: In this analysis, younger patients and older patients demonstrated similar overall rates of genomic alterations. However, younger patients with CRC exhibited an increased rate of alteration in CTNNB1 and MLH1. These data may provide support to explore the WNT signaling pathway as a potential therapeutic target for younger patients with CRC.
Evaluating and treating lesser-income patients with lung cancer in south asia: Where are the delays?
Authors: Vishal Vashistha, Chandrashekhar Choudhari, Avneet Garg, Aditi Gupta, Gopanandan Parthasarathy, Deepali Jain, Karan Madan, Vijay Hadda, GC Khilani, Randeep Guleria, Anant Mohan
Journal: Journal of Clinical Oncology (2018)

e21094 Background: The delays toward the diagnosis and management of lung cancer likely contribute to considerable morbidity and mortality among lesser income patients in the developing world. We sought to identify the time to evaluate symptoms and treat lung cancer in the contemporary era at a public tertiary referral center in northern India before and after the creation of a dedicated lung cancer clinic (LCC). Methods: A retrospective review of patients diagnosed with lung cancer between January 1, 2008 and December 31, 2016 was completed. Evaluation durations were defined as the time intervals between symptom onset, definitive diagnostic investigation, date of confirmed diagnosis, and referral to our facility. Treatment durations were defined as the time intervals between diagnosis and initiation of chemotherapy. Comparisons of median days and inter-quartile ranges were conducted using the Kruskal-Wallis test. Durations were assessed in relation to baseline demographics and the creation of a LCC in January 2012. Results: 1370 patients were selected, with majority (94.5%) having stage III or IV disease. Following the creation of a formal LCC, the mean referrals per month increased (5.1 +/ - 2.3 vs. 18.6 +/- 9.4, p < 0.0001). Following symptom onset, patients required 101 [56 – 168] days to undergo a definitive diagnostic study, 107 [60 – 173] days to obtain a histologic diagnosis, and 120 [75 – 180] days to undergo referral at our center, respectively. The time to initiate chemotherapy following diagnosis increased after January 2012 compared to pre-2012 (21 [12 – 35] days vs. 17.5 [9.5 – 26.8] days, p = 0.018). Chemotherapy was significantly delayed in patients treated for tuberculosis following symptom onset compared to those who were not (187 [134 – 261.5] days vs. 113 [75 – 180] days, p < 0.0001). Conclusions: A large majority of lesser income patients at our facility present with advanced disease. Despite the creation of a dedicated LCC at a public tertiary center, early reliance on alternative diagnoses such as tuberculosis and a growing volume of patients limits the expedition of evaluation and treatment.
Systematic review of resection rates and clinical outcomes after FOLFIRINOX-based treatment in patients with locally advanced pancreatic cancer.
Authors: Steffi Rombouts, Marieke Walma, Jantien A. Vogel, Lennart van Rijssen, Johanna Wilmink, Nadia Haj Mohammad, Hjalmar van Santvoort, I. Quintus Molenaar, Marc G Besselink
Journal: Journal of Clinical Oncology (2016)

4115 Background: FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with LAPC. Furthermore, it may convert a substantial number into resectable tumors. Previous studies combined patients with LAPC and borderline resectable pancreatic cancer, which hampers the interpretation of outcomes with FOLFIRINOX in LAPC. The aim of this review was to provide an overview of the (R0) resection rate and clinical outcomes after FOLFIRINOX-based therapy for locally advanced pancreatic cancer (LAPC). Methods: PubMed, Embase and the Cochrane library were systematically searched for studies published up to August 31st, 2015. Primary outcome was the (R0) resection rate. Results: Fourteen studies involving 365 patients with LAPC were included. A modified chemotherapy regimen was described in 3 studies and FOLFIRINOX dose reductions in up to 65% of patients. Radiotherapy was given in 57% of all patients. Total resection rate was 28% (77% R0) with a peri-operative mortality of 3%. Median overall survival ranged from 8.9 to 25.0 months. Median survival after resection was 24.9 months, based on one study. In total, 6 out of 85 (7%) resection specimens with available data showed a complete pathologic response. Grade 3 to 4 toxicity occurred in 23% of patients. Data of patients treated with FOLFIRINOX without radiotherapy were available from 292 patient: resection rate was 12% (70% R0) with 15.7 months median overall survival and 19% grade 3 to 4 toxicity. Conclusions: FOLFIRINOX-based treatment for patients with LAPC seems safe and achieves high (R0) resection rates and overall survival, despite the frequent administered modified regimes and dose reductions during treatment.
First results of a prospective national controlled study: Prophylactic Radical Fimbriectomy (NCT01608074), in women with a hereditary familial risk of breast/ovarian cancer—Tolerance and pathological findings.
Authors: Eric Leblanc, Fabrice Narducci, Delphine Hudry, Lucie Bresson, Jean-Yves Charvolin, Gwenael Ferron, Frederic Guyon, Virginie Fourchotte, Eric Lambaudie, Marc Baron, Yves Fouche, Sebastien Gouy, Pierre Collinet, Frederic Caquant, Christophe Pomel, Francois Golfier, Veronique Vaini-Cowen, Anne-Sophie Lemaire, Emmanuelle Tresch-Bruneel, Perrine Vuagnat
Journal: Journal of Clinical Oncology (2018)

5574 Background: Risk-reducing salpingo-oophorectomy is the gold standard to prevent the development of a pelvic high grade serous carcinoma (HGSC) in women at risk of breast/ovarian cancer. However, some are reluctant to perform this surgery due to significant related adverse effects. Most of HGSCs stem from the distal fimbrial part of fallopian tubes. Thus we suggested a new prophylactic procedure called radical fimbriectomy (RF), which consists of the resection of both tubes along with the fimbrio-ovarian junction (attached ovarian fragment), completed at 50 years-old or menopause by a bilateral oophorectomy. We present the first results of this operation focused on perioperative morbidity and pathological observations. Methods: BRCA1/2 carriers or any women with a documented familial risk of breast/ovarian cancer were first counseled to perform a classical laparoscopic RRSO. If they denied, they were offered to enter the RF controlled study. All pathological specimens were examined using the SEE-FIM protocol. Intra- and 30-day post-operative events and pathological data were recorded according to protocol. Results: From January 2012 to June 2014, 121 laparoscopic RF were performed. Intraoperative complications were: 1 laparo-conversion for adhesions and 2 grade I procedural hemorrhages. 20 patients (16.5%) complained of Clavien grade I, and 2 (1.7%) grade II adverse effects. Pathologically, we found one (0.8%) invasive HGSC, two (1.7%) Serous Tubal Intraepithelial Carcinoma (STIC), one (0.8%) Serous Tubal Intraepithelial Lesion (STIL) and 21 (17.7%) p53 signatures. All lesions were located at the fimbria, except the HGSC found at a tubal isthmus. Conclusions: In this cohort, 2.5% of patients had a diagnostic of occult tubal neoplasia, as observed in the literature. Tubal examination by a trained pathologist, using SEE-FIM protocol, is necessary to detect precancerous lesions. A longer time is still necessary to report the efficacy of RF in terms of cancer prevention. Meanwhile, we can conclude that RF is safe, well tolerated and effective in term of occult neoplasia detection. Clinical trial information: NCT01608074.
A multicenter phase II study of donafenib in patients with advanced hepatocellular carcinoma.
Authors: Feng Bi, Meng Qiu, Xiaoli Chai, Junqi Niu, Yanhua Ding, Yuxian Bai, Lihua Wu, Jianzhong Shentu, Ping Hao, Jinfei Chen, Qiu Li
Journal: Journal of Clinical Oncology (2017)

e15682 Background: In an early dose-escalation study, Donafenib, a new oral multikinase inhibitor, showed antitumor activity and favorable tolerability in treatment of different type solid tumors including HCC at both 0.2g bid and 0.3g bid dose levels. This prospective study aimed to evaluate the safety and efficacy of Donafenib in the patients with advanced HCC. Methods: In this phase 2 study, patients with unresectable HCC, who had Child-Pugh class A liver function and received no prior systemic therapy were enrolled across 10 sites in China. All patients received oral Donafenib 0.2g bid or 0.3g bid for several 4-week cycles, based on 1:1 randomization ratio. The radiology assessment was done every 8 weeks. The primary end points were safety and tolerability; secondary endpoints were time to progression assessed by an independent radiology committ, ORR , DCR, and PK. Results: Between June 17, 2014, and May 4, 2015, total 106 patients were enrolled and included in the safety analyses. Of them, 52 received donafenib 0.2g bid and 54 received 0.3g bid. The most common adverse events that led to dose discontinuation or reductions were hand-foot skin reaction in 10 (9.4%) patients (2 vs 8), liver dysfunction in 4 (3.8%) patients (1 vs 3), and leukopenia in 2 (1.9%) patients (1 vs 1). Other reported AEs caused dose reductions were hypertension, thrombocytopenia, throat ache, and cough. The median duration maintained for the initial dose was 90 and 72 days, respectively. The full analysis set for TTP includes104 patients (51and 53, respectively) and the per-protocol analysis set for ORR and DCR includes 84 patients (40 and 44, respectively). Median TTP was 111 days in 0.2g group compared with 110 days in 0.3g group (HR 0.99, 95% CI [0.62, 1.60]). At the Week 16, there were no complete responses in both groups, but partial response was confirmed in 4 (4.8%) patients (2 vs 2); and stable disease was in 35 (41.7%) patients (17 vs 18). Conclusions: Donafenib 0.2g bid and 0.3g bid were well tolerated. Significant adverse events were reported more frequently in 0.3g group. Both regimens showed similar treatment responses for patients with HCC, while 0.2g bid seems to be an appropriate first line therapeutic option for the treatment of HCC. Clinical trial information: NCT02229071.