tbuckley/cabot-search huggingface dataset:
Epidemiological profile of lung cancer in a Nepalese population: A single-institution review.
Authors: Madan Kumar Piya
Journal: Journal of Clinical Oncology (2019)

e13087 Background: Lung cancer is one of the common cancers worldwide, and is the commonest cancer in Nepal, with an incidence of 16%. There is a high incidence of smoking in Nepal, being highest in the mountain region in the north and lowest in the tarai region in the south. Smoking kills around 15,000 people per year. The prevalence of smoking in the urban population of Kathmandu over the age of 15 has been estimated at 64.6% in men and 14.2% in women. Nepal has diverse population with various ethnicities and different cultures. The aim of this study was to determine the relation of smoking, epidemiology of lung cancer and distribution of lung cancer in various ethnicities of Nepal. Methods: All patients attending National Hospital and Cancer Research Center in Kathmandu who were diagnosed with lung cancer between January 2012 and December 2018 were enrolled in the study. Informed consent was taken before enrollment and data was collected by the nursing staffs prospectively using a preset questionnaire for interviewing patients. Results: Data was collected from 250 patients over the seven years with histologically proven lung cancer. About 85.6 % of patients were male and 80% of them were smokers. 50% of men and 30 % of the women were smokers. Most common age to start smoking was in 11-20 years group (60%). 58% of patients were from Kathmandu valley, and 42% of patients from outside the valley. 38% of male were literate and 16% were illiterate where as 13.6% of female were literate and 32.4% were illiterate. Among the various ethnic groups, 44% were Newars, 20% Mongols, 18% in Chhetris and 18% Brahmins. The incidence of lung cancer was highest (57.6%) in the age 61-80 years age group. 14.4% of the patients had family history of cancer M = 8.6% and F = 6.0%). Squamous cell carcinoma was the highest (51.2%) followed by small cell carcinoma (22%) and adenocarcinoma (26.8%). Carcinoma of right lung was frequent (62%) compared to the left lung (38%). Local cigarette were used by 82.5% of the smokers and 54.5% of them used filtered cigarettes. 40% practiced relighting the butt ends. Conclusions: The study shows that smoking is a single major contributing factor observed in lung cancer in Nepal across various age groups as well as diverse ethnic groups. Given the high incidence of smoking starting before the age of 20, there is an urgent need for organized mass anti-smoking campaigns, especially in schools targeting the younger age group. Need of awareness against the smoking and the cause of lung cancer needs to emphasized to reduce the burden of the lung cancer.
Elucidation of PARP inhibitor activity in BRCAwt recurrent ovarian cancer by hrr mutational gene profile analysis.
Authors: Mansoor Raza Mirza, Bin Feng, Ming Shan, Kaiming Sun, Ilkar Yalcin, Kevin Coleman, Kenneth S. Thress, Sebastien Hazard, Jing Y. Wang, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2019)

5568 Background: Niraparib is an oral, selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved for maintenance treatment of BRCA mutated ( BRCAmut) and BRCA wild-type ( BRCAwt) recurrent ovarian cancer patients (pts) who are in response to platinum-based chemotherapy. In the non-germline BRCA mutated (non-g BRCAmut) cohort of the ENGOT-OV16/NOVA trial, clinical benefit with niraparib vs placebo was seen in pts regardless of their Myriad myChoice HRD test status ( BRCAmut and homologous recombination deficiency [HRD] score), with a hazard ratio (HR) of 0.38 in HRD-positive (HRDpos) and 0.58 in HRD-negative (HRDneg) pts. To determine if treatment benefit in HRDneg pts may result from mutations in other homologous recombination repair ( HRR) genes, we examined the relationship between progression-free survival and other HRR gene mutations in the NOVA non-gBRCAmut cohort. Methods: A retrospective, exploratory biomarker analysis was conducted using all available tumor samples from 331 pts enrolled in the NOVA non-g BRCAmut cohort. Mutation status of HRR genes was evaluated using a 43-gene NGS assay (Myriad Genetics), including BRCA1/2 and 16 additional HRR genes. Results: In this exploratory analysis of the NOVA non-g BRCAmut cohort, niraparib demonstrated clinical benefit in pts with somatic BRCA mutation (HR, 0.27) and in BRCAwt pts (HR, 0.47). In addition, BRCAwt pts with other HRR gene mutations also derived benefit from niraparib (HR, 0.31), as did BRCAwt/ HRRwt pts (HR, 0.49). When BRCAwt/ HRRwt pts were categorized by HRD score, clinical benefit was also observed in both HRDpos and HRDneg pts, with HRs of 0.33 and 0.60, respectively. These results suggest that, although these biomarkers have good positive predictive value, they are not good negative predictors for niraparib benefit in this indication. Conclusions: This retrospective, exploratory analysis of the ENGOT-OV16/NOVA non-g BRCAmut cohort suggests that although pts with somatic BRCA mutation and other HRR mutations benefit from niraparib treatment, clinical benefit is also seen in HRDneg pts without HRR mutations, perhaps related to other genomic, epigenetic, or functional alterations within ovarian tumors yet to be defined.
Low dose enzalutamide in metastatic castration-resistant prostate cancer: A retrospective Caribbean study.
Authors: Vincent Vinh-Hung, Kadiatou Diakite, Clarisse Joachim, Stefanos Bougas, Cristina Ioana Furtos, Jean-Marc Rakotonarivo, Wadah Lababidi, Eva Papadopoulou, Patrick Escarmant, Jacqueline Veronique-Baudin, Claire F. Verschraegen
Journal: Journal of Clinical Oncology (2019)

e16548 Background: There is scarce information on the efficacy of low-dose enzalutamide in metastatic castration-resistant prostate cancer. We report on a series treated with half dose enzalutamide. Methods: We observed a trend in our practice to initiate low-dose enzalutamide at the time of disease progression in older patients considered frail, presenting with cardio-vascular comorbidity or with history of neurological symptoms. Records were retrospectively reviewed. The selection criteria were: 1) Metastatic disease demonstrated by at least one imaging modality, CT, bone scan, or positron emission tomography. 2) Progression of prostate specific antigen (PSA). 3) Castrate testosterone level ( &lt; 0.2 ng/mL). 4) Enzalutamide treatment at 80 mg or less, once daily. To estimate the rate of PSA response, we used linear interpolation to compute the time from the initiation of low-dose enzalutamide to 50% PSA reduction. Results: Between November 2015 and December 2018 at the Martinique University Hospital, 10 patients matching the selection criteria were treated with ≤ 80 mg enzalutamide od: 8 started de novo with the low dose, 2 started with 160 mg but required dose reduction for intolerance. The mean age was 78 years (range 67-84). Three had painful bone metastases. The mean PSA at start of low dose enzalutamide was 88 ng/mL (range 1.06 - 251.8). All patients were maintained with reduced dose. At the current follow-up of 9 months (range 0 - 36 months), PSA response was observed in 7 patients ( = 70%), 1 was not evaluable (PSA not assessed), 2 did not respond. Of the 2 non-responders, one had no sign or symptom of disease progression; the other presented with extensive disease progression previously treated with abiraterone, he refused to receive increased dose enzalutamide. Among the 7 responders, the time to 50% PSA reduction was 57 days (range 26 - 119). Currently, the decline of PSA remains sustained in 6 of the 7 responders, it increased in 1 who discontinued enzalutamide. Pain decreased in the 3 symptomatic patients, including the PSA non-responder. Conclusions: Low dose enzalutamide appears efficient in a large proportion of selected frail patients. Further follow-up is required to evaluate the long-term response.
Case 25-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Jerome P Richie, Lewis A. Hassell
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 27-year-old man was admitted to the hospital because of hematuria.He was well until 13 years earlier, when total, gross, painless hematuria developed several hours after trauma to the left flank in a bicycle accident. He was seen at another hospital, where results of bleeding studies were normal, and an intravenous urographic examination was negative. Cystoscopic examination showed that bleeding was limited to the left ureteral orifice; a voiding cystourethrographic study and an angiographic examination were also negative. Hematuria persisted, and four months later he returned to the same hospital, where repeated cystoscopic and retrograde pyelographic . . .
Survival outcomes of premenopausal patients diagnosed with invasive lobular carcinoma.
Authors: Hee Jeong Kim, Seon-Ok Kim, Rachel A. Freedman, Ann H. Partridge, Otto Metzger-Filho
Journal: Journal of Clinical Oncology (2019)

1093 Background: The survival outcomes of postmenopausal women with invasive lobular carcinoma (ILC) are similar to invasive ductal carcinoma (IDC) when treated with aromatase inhibitor, but inferior when treated with tamoxifen. We sought to investigate the survival outcomes of premenopausal ILC when compared to IDC using a population-based analysis. Methods: We used Surveillance, Epidemiology, and End Results data (SEER) between 1990 to 2015 to identify premenopausal patients (defined as &lt; 50 years old), diagnosed with stage I to III IDC or ILC. Breast Cancer Specific Survival (BCSS) was assessed using log-rank test and piecewisecox models. Annual hazard of BCCS for hormone receptor positive (ER+) ILC and ER+ IDC were calculated from year 0 to 20 and defined as the proportion of patients with a BCSS event during a 1-year interval. Results: The study includes a total of 170,352 pts diagnosed with either IDC (n = 158,733) and ILC (n = 11,619). 71% of IDC and 95% of ILC pts were ER+. Median age was 44 years old and median follow up was 90 months(IQR 40-151 months). Survival analysis revealed a significant time-dependent effect of histology for BCSS (p &lt; .0001). When compared to IDC, ILC pts had better BCSS in the first 10 years after diagnosis (HR 0.73, 95% CI 0.68-0.78), but worse BCSS outcome after year 10 (HR 1.80, 95% CI 1.59- 2.03). Similar results were observed when adjusting for ER status, histologic grade and stage on multivariate analysis. Among pts ≤ 35 years old(n = 371 ILC; 18086 IDC) survival analysis revealed a non-significant trend towards inferior outcome for ILC compared to IDC throughout the whole follow-up period (HR = 1.2 95% CI 0.96-1.52). Annual hazard of BCCS events showed a peak at year 5 for both IDC and ILC. In the subset of IDC, we noticed a decreasing hazard of BCSS from years 6 through 20. By contrast, in the subset of ILC, we observed higher frequencies of BCSS from years 6-20 when compared to IDC (p &lt; 0.0001). Conclusions: In this population-based analysis, premenopausal ILC had worse BCSS estimates when compared to premenopausal IDC. This is explained by a higher incidence of late events in the subset of ILC when compared to IDC.
Randomized phase Ⅱ trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage Ⅲ non-squamous non-small-cell lung cancer: NJLCG1001.
Authors: Kana Watanabe, Yukihiro Toi, Atsushi Nakamura, Tatsuro Fukuhara, Ryosuke Chiba, Masachika Akiyama, Jun Sakakibara-Konishi, Hisashi Tanaka, Naruo Yoshimura, Eisaku Miyauchi, Taku Nakagawa, Ryotaro Igusa, Hiroyuki Minemura, Yoshiaki Mori, Keisuke Fujimoto, Haruo Matsushita, Fumiaki Takahashi, Akira Inoue, Shunichi Sugawara, Makoto Maemondo
Journal: Journal of Clinical Oncology (2019)

8527 Background: It is unknown which regimen is the best in concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC). Our previous randomized phase Ⅱ study, NJLCG0601, showed that chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy with acceptable toxicities. In this trial, this regimen was compared to a regimen with pemetrexed and cisplatin for stage Ⅲ non-squamous NSCLC. Methods: Patients with inoperable stage Ⅲ non-squamous NSCLC were randomized to UFT 400 mg/m 2 on days 1–14 and 29–42, and cisplatin 80 mg/m 2 on days 8 and 36 (UP), or pemetrexed 500 mg/m 2 and cisplatin 75 mg/m 2 on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) was administered from day 1 to a total dose of 66 Gy radiotherapy in 33 fractions. Consolidation chemotherapy after CCRT was not planned for this study. The primary endpoint was 2-year overall survival (OS), with expected rates of 55% and a lower limit of 35% (alfa 0.05, beta 0.2). Secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), OS, and toxicity profile. Results: From November 2010 to June 2017, 86 patients were enrolled from 11 institutions. Of the 85 eligible patients, the rate of 2-year OS was 78.6% (95% CI: 62.8–88.3%) in the UP arm and 85.5% (95% CI: 70.5–93.2%) in the PP arm. The ORR was 76.7% in the UP arm and 81.0% in the PP arm. With a median follow-up of 54 months, median PFS and OS were 12.3 and 64.2 months in the UP arm, and 26.2 months and not reached in the PP arm, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP arm than in the PP arm (14.0%, 2.0%, respectively). Grade 3/4 pneumonitis occurred in 7.0% and 4.8% of patients in UP and PP arms, respectively. Conclusions: Both regimens with IFRT achieved the expected 2-year survival rate. PP had more favorable results than UP in terms of OS and PFS. We selected the PP arm for the next step.
Real life data from Turkey regarding the impact of first-line sunitinib and pazopanib in metastatic renal cell cancer.
Authors: Ulas Isik, Osman Kostek, Gokcen Demiray, Ahmet Dirican, Melih Simsek, Mahmut Büyüksimsek, Gokhan Ucar, Ulug Mutlu Gunaydin, Teoman Sakalar, Altay Aliyev, Atakan Demir, Serdar Turhal, Kezban Nur Pilanci, Umut Kefeli, Ali Gokyer, Semra Paydas, Dogan Uncu, Ilker Nihat Okten, Kazim Uygun, Devrim Cabuk
Journal: Journal of Clinical Oncology (2019)

e16075 Background: Although the distribution in the world varies widely, renal cell carcinoma (RCC) is the ninth most common cancer, especially in males. It’s the seventh most common cancer in Turkey. In this study, the progression-free survival (PFS) and overall survival (OS) of patients with metastatic RCC (mRCC) who were treated at 13 centers in our country were evaluated and the efficacy of first-line treatment approaches was compared. Methods: Data of mRCC patients admitted to 13 outpatient clinics in Turkey between 2008 and 2018 were reviewed retrospectively. Demographic characteristics, pre-treatment clinical evaluations, information about treatment approaches and survival outcomes of the patients were collected. All medical records were collected by a detailed review of the patients’ charts. The median and percentage values were frequently signified for defining of central trends. Kaplan-Meier method was applied for OS analyzes and log-rank test with Cox-regression models were applied for the evaluation of prognostic factors. Results: Data from files of 262 patients were reviewed. Twelve of these patients were excluded from the study because they could not receive treatment due to comorbidities and other reasons at metastatic stage of the disease. Of the patients, 100 (40%) were female and 150 (60%) were male. Median age was 60 (range 21-83). For the entire group, the median PFS (mPFS) was 27.6 months and the median overall survival (mOS) was 46.1 months. In terms of first-line treatment of metastatic disease, 41.3% of the patients received sunitinib, 48.8% of the patients received pazopanib, 15.8% of the patients received other treatments. PFS of the patients receiving sunitinib, pazopanib and the other treatments were 26.3 months, 34.2 months and 14.2 months, respectively. There was no statistically significant difference between PFS of the patients receiving sunitinib and pazopanib (p = 0.05). mOS was 54 months in sunitinib arm, 54.9 months in pazopanib arm and 23.3 months in the other treatment arm. There was no statistically significant difference between two treatment agents in terms of mOS (p = 0.43). Conclusions: Pazopanib was more commonly prescribed in Turkey. There were no statistically significant differences between mPFS and mOS of the patients who received sunitinib and pazopanib for the first-line treatment of mRCC. With increased use of immunotherapeutic agents for the first-line treatment of mRCC in our country, improvement in mOS could be expected.
Ethics consultations in patients with neuro-oncologic diseases.
Authors: Ugur Sener, Elizabeth C. Neil, Alan Carver, Eli L. Diamond, Louis Voigt
Journal: Journal of Clinical Oncology (2019)

e13519 Background: In patients with cancer, ethical issues regarding patient autonomy, surrogate decision making, and end-of-life care often arise. Ethics consultation can help clarify perspectives of different stakeholders involved in a patient’s care, facilitate communication, and resolve conflicts. Neurologic manifestations of cancer can cause impairment of cognition, communication, and functional independence. Ethical conflicts in the specific context of neuro-oncologic diseases have yet to be characterized. Methods: In this retrospective study, we reviewed 50 cases where ethics consultation was requested for patients with neurologic malignancies or neurologic complications of cancer treated at Memorial Sloan Kettering Cancer Center (MSK). Results: Of 50 patients (ages 4-76, 56% female) reviewed, 27 had a primary central nervous system (CNS) malignancy, 21 had CNS metastasis, one had a vascular malformation, and one had no clear diagnosis. Neurologic issues contributing to patients’ clinical status included toxic metabolic encephalopathy (14), leptomeningeal disease (10), intracerebral hemorrhage (10), hydrocephalus (9), seizures (6), cord compression (5), and ischemic stroke (3). At the time of ethics consultation, 39 patients lacked decision-making capacity, 47 did not have an advance directive, and 38 did not have a do not resuscitate (DNR) order. Ethical issues identified included surrogate decision making (20), DNR (18), capacity (6), refusal of treatment (5), futility (4), brain death (4), and research ethics (2). Contextual issues included staff-family conflict (22), cultural or religious considerations (10), intra-family conflict (7), intra-staff conflict (6), and physician attitude toward treatment (3). Conclusions: Neuro-oncologic diseases present a unique constellation of ethical conflicts, particularly about end-of-life care. Language and cognitive deficits, impaired decision-making, and sudden neurological decline are factors that shape ethical conflicts in this clinical setting. Further study of ethical issues in neuro-oncology may help patients receive care that is consistent with their goals and values.
Tabelecleucel in combination with pembrolizumab (Pembro) in platinum-pretreated, recurrent/metastatic Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (EBV+NPC).
Authors: Lillian L. Siu, Joshua Bauml, Douglas Adkins, A. Dimitrios Colevas, Cesar Augusto Perez, Jennifer Hsing Choe, Yang Zhang, Wen Shi, Willis H. Navarro, Missak Haigentz, Guilherme Rabinowits, David G. Pfister
Journal: Journal of Clinical Oncology (2019)

TPS6092 Background: Approximately 25% of patients (pts) with NPC develop RM disease, which has a poor prognosis (median overall survival [mOS]: 12–16 mo), despite standard treatments with radiation and/or chemotherapy. NPC is an EBV-associated cancer in which programmed cell death ligand 1 (PD-L1) expression is upregulated upon EBV activation. Pembro showed antitumor activity in a phase 1b study of pts with RM-NPC (objective response rate [ORR]: 26%; mOS: 16.5 mo) (Hsu, J Clin Oncol 2017;35:4050-56). Targeting RM EBV+ NPC with tab-cel immunotherapy (off-the-shelf, allogeneic EBV-specific T cells) in pts has also shown promise, with 2-yr OS rates of 84% (Prockop, ASCO 2016;34:3012). The favorable safety profile of tab-cel offers the opportunity for combination immunotherapy with pembro for increased efficacy. Methods: This multicenter, open-label, single-arm phase 1b/2 study evaluates safety and efficacy of tab-cel in combination with pembro. Study participants are ≥12 yrs of age with incurable, locally recurrent or metastatic EBV+ NPC previously treated with platinum-containing therapy. Pts are checkpoint-inhibitor naïve (phase 1b/2) or refractory to anti-PD-1 or anti-PD-L1 therapy (phase 1b). Tab-cel is selected from a bank based on matching ≥2 HLA alleles, including ≥1 restricting HLA allele, between pts and donors. Tab-cel will be administered intravenously (IV) on days 1, 8, and 15 of a 21-day cycle. Initial tab-cel dose is 2x10 6 cells/kg and the de-escalated tab-cel dose (if needed) is 1x10 6 cells/kg. Pembro is administered at 200 mg IV Q3W in adults and 2 mg/kg IV Q3W in pts aged 12 to 17 yrs. Primary outcomes of phase 1b are to characterize dose-limiting toxicities, identify the maximum tolerated dose (MTD) or in the absence of MTD, the recommended phase 2 dose, and assess safety. Primary outcomes for phase 2 are ORR and safety. Secondary endpoints include progression-free survival, OS, and duration of response. Enrollment is ongoing for 12-24 participants in the phase 1b portion of the study with a 6+6 design. Phase 2 is expected to enroll 36 pts. Clinical trial information: NCT03769467.
Oncotype recurrence score (RS) and discordance in patients with secondary invasive breast events (SIBE).
Authors: Brittney Shulman Zimmerman, Krystal Pauline Cascetta, Julia Blanter, Lauren Eggert, Madeline Molot, Meng Ru, Anupma Nayak, Ira Bleiweiss, Shabnam Jaffer, Amy Tiersten
Journal: Journal of Clinical Oncology (2019)

e12016 Background: Oncotype RS is a 21-gene assay used to predict the likelihood of distant recurrence and benefit of chemotherapy in patients with node-negative, tamoxifen treated breast cancer (BC). We developed a database to determine rates of SIBE and identify cases of discordance between Oncotype RS and tumor grade (TG). Our goal was to recognize patients with discordant tumors who had SIBE, with implications for patient management. Methods: We identified 618 patients (645 samples) with early-stage, hormone positive BC treated between 2006-2018, with tumor characteristics available for analysis. Among these patients, there were 24 SIBE (n = 24) from 23 patients (3.7%). When stratified by RS using traditional cutoffs (Paik, 2004), rates of SIBE were 2.8%, 5.0% and 4.5% in low, intermediate and high-risk groups respectively. Discordance was defined as 1 or 2-step difference between RS (low, intermediate, high risk) and TG (well (WD), moderately (MD) and poorly (PD) differentiated). Prior studies demonstrated 7-19% “2-step discordance” between TG and RS (i.e. PD tumors with low-risk RS or WD tumors with high-risk RS). N(%) or median were used to describe patients’ characteristics between groups and compared by Mann-Whitney U test at the confidence level of 5%. Results: Of the 24 SIBE, 42% had low RS ( &lt; 18), 46% had intermediate RS (18-30) 12% had high RS ( &gt; 31). Median RS was 22 and median age at secondary event was 61 (67% post-menopausal). At time of SIBE, 54% were metastatic, 25% locally recurrent and 21% contralateral. Within this dataset, 63% were 1-step and 4% were 2-step discordant. Significantly fewer patients were treated with systemic chemotherapy in the discordant group (p &lt; 0.01), though 94% displayed MD or PD TG. Discordant tumors tended to have lower RS (median 14 vs. 24) and be larger. There were no significant differences in menopausal status or Oncotype ER/PR score. Conclusions: Although the sample size of patients with SIBE is small, our data suggests that patients with discordant tumors of low-risk RS but higher TG may be receiving inadequate treatment (i.e. no chemotherapy). In addition to RS, other factors such as discordance, TG and size should perhaps be considered when determining treatment plans.