tbuckley/cabot-search huggingface dataset:
Real-world (rw) clinical outcomes for advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) treated with second line (2L) ramucirumab plus docetaxel (R+D) post frontline (1L) platinum based chemotherapy plus immune checkpoint inhibitors (Pt + ICI).
Authors: Jeffrey Melson Clarke, Raina Mathur, Cliff Molife, Marta Batus, Victoria Jennifer Stefaniak, Katherine B. Winfree, Shrujal Baxi, Zhanglin Lin Cui, David Lenis, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2019)

e20727 Background: R+D is approved for use in pts with aNSCLC after Pt chemotherapy. With recent approvals, ICI can now be added to Pt chemotherapy (Pt + ICI) in 1L. This retrospective observational study provides an exploratory view of baseline characteristics and rw clinical effectiveness outcomes for pts receiving 2L R+D post 1L Pt + ICI. Methods: All adult pts treated with 2L R+D after 1L Pt + ICI therapy between 03/01/2015 and 06/30/2018, with ≥ 3 months follow up, were selected from the Flatiron Health EHR-derived de-identified database (n = 15). Rw clinical endpoints during R+D therapy included rw objective response rate (rwORR), rw disease control rate (rwDCR), rw best response, as well as Kaplan-Meier estimates of rw time to first response &amp; rw duration of response. Results: Median age was 62 years, 10 pts (66.6%) were aged &lt; 65 years, 11 (73.3%) were men, 3 (20.0%) had no history of smoking, 14 (93.3%) had non-squamous histology, 4 (26.7%) were EGFR positive, 3 (20.0%) were KRAS positive and 6 (85.7%) were PD-L1 negative. Of the 8 pts with a documented rw tumor response assessment, 3 (37.5%) had partial response (PR), 3 (37.5%) had stable disease (SD), &amp; 2 (25.0%) had progressive disease as their rw best response. The rwORR (PR or complete response [CR]) &amp; rwDCR (PR, CR, or SD) were 37.5% and 75.0%, respectively. Among responding pts, median time to first response was 2.2 months (95% CI, 1.3 - not reached [NR]) &amp; median duration of response was 2.3 months (95% CI, 1.5 - NR). Patient numbers were too small (n = 15) and duration of follow-up was too short (3.4 months [IQR, 0.7 - 5.4]) to make robust estimation of overall survival or rw progression free survival. Conclusions: Data from this small patient cohort in US community practice are not conclusive and should be considered exploratory, but do show high rates of rw objective response and rw disease control rates during 2L R+D following 1L Pt + ICI. Data with larger sample sizes and additional follow-up are needed to better understand outcomes of R+D following the addition of ICI to 1L Pt chemotherapy regimens.
Ultrasound elastography: a novel tool for the differential diagnosis of pleural effusion
Authors: Bin Jiang, Xue-lian Li, Yan Yin, Qin Zhang, Tong Zang, Wang-shu Song, Xue-mei Wang, Jian Kang, Felix J.F. Herth, Gang Hou
Journal: European Respiratory Journal (2019)

Traditional thoracic ultrasound (TUS) is often the initial tool used to help diagnose malignant pleural effusion (MPE). Ultrasound elastography, a relatively new technique, has been used to differentiate malignant disease from benign disease by evaluating tissue "stiffness". However, no studies evaluating the efficacy of ultrasound elastography for diagnosing MPE are available. We assessed the value of ultrasound elsatography for diagnosing MPE prospectively.All 244 enrolled patients were divided into a development set and a validation set in chronological order. The cut-off elasticity index was established using a receiver operating characteristic curve constructed from the continuous data of the patients in the development set. The diagnostic performance of ultrasound elastography was compared with that of TUS in the validation set.In the development set, the mean elasticity index (47.25 kPa) was the optimal cut-off. In the validation set, pleural ultrasound elastography had a sensitivity of 83.64%, a specificity of 90.67%, a positive predictive value of 86.79%, a negative predictive value of 88.31%, a positive likelihood ratio of 8.96 and a negative likelihood ratio of 0.18 for diagnosing MPE. The sensitivity of ultrasound elastography was significantly higher (p=0.006) than that of TUS (60%).Pleural ultrasound elastography is a better technique than TUS for differentiating MPE from benign pleural disease.
Preliminary result of phase II study of megestrol combined with 5-hydroxytryptamine 3 inhibitor and dexamethasone for the prevention of nausea and vomiting induced by high emetogenic chemotherapy.
Authors: Qiong Wu, Suxia Luo, Ning Li, Wenying Deng, Yijie Ma, Xinyi Yang
Journal: Journal of Clinical Oncology (2019)

e23049 Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing treatment-related side effects and have a strong impact on treatment adherence. A triplet antiemetic regimen, which is composed of neurokinin-1 receptor antagonist (NK 1 RA), 5-hydroxytryptamine 3 (5-HT3) inhibitor and dexamethasone, is recommended by current antiemetic guidelines. However, NK 1 RA is not available in hospital and more expensive for Chinese patients. Megestrol is currently known as more effective appetite stimulants in patients with cachexia or loss of appetite, but its antiemetic properties are less well known. Therefore, the aim of this study was to further evaluate the efficacy and safety of megestrol for the prevention of CINV. Methods: Patients treated with high emetogenic chemotherapy (HEC) were randomly divided into experimental group and control group. The antiemetic regimen of control group: 5-HT3 inhibitor 5mg/d, dexamethasone 12mg/d1, 8mg/d2-4. The regimen of experimental group: the use of 5-HT3 inhibitor and dexamethasone was the same as that of control group, and each patient took megestrol 160mg orally from the first day of chemotherapy for 10 days. Digestive tract reactions were daily evaluated after beginning of HEC. Primary end point was rate of complete response to vomiting and nausea. Results: From September 7 to December 31, 2018, 60 patients were enrolled and randomized in the study. The delayed nausea and vomiting rates were significantly lower in experimental group than control group (nausea: 63.3% vs 83.3%; vomiting: 13.3% vs 33.3%; p&lt; 0.00). The control group was significantly higher rate of Grade 3-4 vomiting than that of the experimental group (20% vs 0%, p&lt; 0.01). Conclusions: Megestrol, combined with dexamethasone and 5-HT3 inhibitor, has been shown to be able to successfully control CINV and no increase side effects during HEC. Clinical trial information: ChiCTR1800017953. [Table: see text]
Adjuvant Therapy for Ampullary Cancer
Authors: Andrew H. Ko, Eric K. Nakakura
Journal: JAMA Surgery (2019)

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Case 42-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Nicholas S. Hill, Eugene J. Mark
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 61-year-old man was admitted to the hospital because of increasing dyspnea.He was well until five years earlier, when palpitations developed. Three and a half years before admission he began to experience progressive exertional dyspnea. Three years before entry the dyspnea worsened. He was seen at another hospital, where x-ray films of the chest were reported to show slight cardiac enlargement with evidence of pulmonary hypertension; no sign of a left-to-right shunt was seen. The dyspnea worsened further, and 34 months before entry an electrocardiogram showed a normal rhythm, incomplete right bundle-branch block, and right atrial . . .
Bevacizumab (BV) maintenance (M) after first-line chemotherapy (CT) plus BV for metastatic colorectal cancer (mCRC) patients (pts): A meta-analysis of individual pts data (IPD) from three phase III studies.
Authors: Lisa Salvatore, Emilio Bria, Isabella Sperduti, Axel Hinke, Susanna Hegewisch-Becker, Thomas Aparicio, Karine Le Malicot, Valerie Boige, Dieter Koeberle, Daniela Baertschi, Daniel Dietrich, Giampaolo Tortora, Dirk Arnold
Journal: Journal of Clinical Oncology (2019)

3550 Background: Although CAIRO3 and AIO KRK 0207 trials demonstrated the benefit of BV + fluoropyrimidine as a M regimen after induction CT + BV, the role of BV alone is not clear. Indeed, SAKK 41/06 and PRODIGE 9 trials failed to demonstrate the superiority of BV alone vs no M, while AIO KRK 0207 showed the non-inferiority of BV alone vs combo M. Thus, in order to evaluate the magnitude of the eventual benefit of M with BV alone vs no M, an IPD meta-analysis was performed. Methods: Trials whereas mCRC pts were prospectively randomized to receive BV M or not were considered eligible. Primary end-points were PFS and OS, both from the start of induction and M. Univariate and multivariate analyses for PFS and OS were performed, with the following variables: baseline ECOG PS; age ( &gt; vs ≤ 65 years); RAS and BRAF status; LDH and CEA baseline level; RR (PR or CR vs SD) during induction; induction CT (oxa- vs iri-based); resected primary tumor; primary tumor side; synchronous vs metachronous; adjuvant treatment; number (N) of metastatic sites; liver-only disease. Results: IPD of 1,064 pts enrolled in the PRODIGE 9, AIO KRK 0207 and SAKK 41/06 trials were collected. Considering the different timing of randomization in PRODIGE 9 (at the start of induction) vs AIO KRK 0207 and SAKK 41/06 (at the start of M), IPD of pts not progressed during induction and starting M phase entered the analysis. 909 pts were included, 457 (50%) received BV M. Median PFS from induction start was 9.6 and 8.9 months in BV group vs no M group, respectively (HR 0.78; 95%CI: 0.68-0.89; p &lt; 0.0001). At the multivariate PFS analysis, BV M, resected primary tumor, N of metastatic sites and liver-only disease were significant. No difference in terms of OS between the 2 groups was observed. Conclusions: This is the first IPD meta-analysis investigating the role of BV alone M vs no M after first-line induction CT+BV in mCRC pts. Despite the significant PFS improvement in favor of BV M, the absolute benefit appears limited, and without a clear clinical relevance. On these bases, a predictive nomogram to identify pts most likely to benefit from BV M is under evaluation and will be presented during the Congress.
Clinical characteristics and treatments outcomes of patients with metastatic uveal melanoma (UM) in a Brazilian population: A retrospective unicentric study.
Authors: Giovanna Campiolo, Milton Jose De Barros E. Silva, Mariana Petaccia de Macedo, Jose Augusto Rinck
Journal: Journal of Clinical Oncology (2019)

e21018 Background: Uveal melanoma is the most common primary ocular tumor in adults and accounts for 5% of all melanoma diagnoses in the United States. Approximately fifty percent of patients with uveal melanoma develop metastatic disease. The most frequent site of metastasis from UM is the liver (89 to 95% of the cases) and liver failure is the leading cause of death. To date, no systemic therapy has shown benefits in terms of overall survival (OS) in UM. Methods: We retrospectively analyzed clinical characteristics and aspects of response to systemic and local therapy of a cohort of 58 patients with UM who were treated in our institution from January of 2000 to December of 2017. Survival curves were calculated by Kaplan-Meier method and log-rank test. Results: Median age was 55y. 64% of the patients were female and 48,3% of them were caucasian. With a median follow-up time of 23 months, the median OS was 28,4 months. The median time between primary treatment and systemic relapse was 3.7 years. In 90% of the cases the liver was the unique site of progression. 12% patients had liver metastasectomy as local treatment, with OS of 102,3 months vs. 24,5 months ( p= 0,04) for no local treatment. 12% of the patients with liver methastasis perfomed regional treatment with intra-arterial chemotherapy (IAC) and 17% with chemoembolization (CE). The progression free survival (PFS) for regional treatment was 2.9 months (0,9-27 m); 4,25 months (0,9-27 m) for IAC and 2,9 months (0,9-27 m) for CE. There was no significant benefit in OS for locorregional treatment. As first line treatment, 29% of patients had chemotherapy, 10% had ipilimumab and 3,4% had anti-PD1. The median PFS for first line treatment was 2,49 months; 2 months for chemotherapy, 3,8 months for ipilimumab and 14 months for anti-PD1. The median PFS for second line treatment was 2,8 months and for third line was 2,3 months. There was no consistent clinical impact in OS for systemic treatment. Conclusions: The current systemic treatments available for cutaneous melanoma have limited efficacy in UM, so far none have yet proven a survival benefit. Locorregional therapies are relevant for patients with unresectable hepatic metastases. Resection of liver lesions in highly selected cases has the potential to improve patient outcomes, but the survival advantage may partially reflect patient selection.
Comparative effectiveness of proton therapy versus photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer.
Authors: Brian Christopher Baumann, Nandita Mitra, Joanna Harton, Ying Xiao, Andrzej Wojcieszynski, Peter Edward Gabriel, Haoyu Zhong, Huaizhi Geng, Abigail Doucette, Jenny J. Wei, Peter J. O'Dwyer, Justin E. Bekelman, James M. Metz
Journal: Journal of Clinical Oncology (2019)

6521 Background: Concurrent chemo-radiotherapy is standard-of-care curative treatment for many cancers, but is associated with substantial morbidity. Proton therapy may increase the tolerability or effectiveness of concurrent chemo-radiotherapy by reducing radiation to normal tissues. Methods: We conducted a comparative effectiveness study of adult non-metastatic cancer patients treated with curative intent with proton chemo-radiotherapy vs. photon chemo-radiotherapy from 2011-2016 at the University of Pennsylvania. Re-irradiation and disease sites treated with photon-only therapy were excluded. Data on adverse events and survival was gathered prospectively. Primary endpoint was 90-day adverse events associated with unplanned hospitalizations (CTCAEv4 grade ≥3 adverse events). Secondary endpoints included decline in ECOG performance status during treatment, 90-day grade ≥2 adverse events, disease-free survival (DFS) and overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were fit for both outcomes. Propensity scores were estimated using an ensemble machine-learning approach. Results: 1,483 patients were included (391 proton/1,092 photon). Proton patients were significantly older (median 66 vs. 61), had less favorable Charlson-Deyo comorbidity scores (median 3.0 vs. 2.0), and had lower integral radiation dose to tissues outside the target (p &lt; 0.05 for all). Baseline toxicity and performance status were similar (p &gt; 0.05). In propensity score weighted-analyses, proton chemo-radiotherapy was associated with significantly lower relative risk (RR) of 90-day grade ≥3 adverse events [11.5%(95%CI 8.3-14.7%) for protons; 27.6%(95%CI 24.9-30.2%) for photons; RR 0.31, 95%CI 0.15-0.66, p &lt; 0.01]; 90-day grade ≥2 adverse events (RR 0.78, 95%CI 0.65-0.93, p &lt; 0.01); and decline in performance status during treatment (RR 0.51, 95%CI 0.37-0.71, p &lt; 0.01). There was no difference in DFS or OS. Conclusions: In adults with locally advanced cancer, proton chemo-radiotherapy was associated with significantly reduced acute adverse events causing unplanned hospitalizations with similar disease-free and overall survival.
Defining tissue requirements for a reliable detection of tumor mutational burden (TMB) in clinical FFPE samples.
Authors: Hans-Ulrich Schildhaus, Thomas Herold, Karl Worm, Oliver Stoss
Journal: Journal of Clinical Oncology (2019)

e14265 Background: In the context of immuno-oncology related cancer treatment, tumor mutational burden (TMB) is currently explored as a predictive biomarker for several human malignancies. Several sequencing assays are increasingly commercially available. Established methodologies require rather large amounts of DNA input (in the range of 100 ng) which, however, are frequently not available from small biopsies. We aim to investigate how tissue size and DNA input influence TMB scores. Methods: DNA from 20 specimens (12 biopsies of non-small cell lung cancer (NSCLC); 8 surgical resection specimens from NSCLC, colorectal cancer and endometrial carcinomas) was manually extracted by using the Qiagen GeneRead DNA FFPE kit. Cases were selected to provide a wide range of relative tumor cell content (from &lt; 10% to &gt; 50%) and to include microsatellite-stable and –instable (MSI) cases. Samples were analyzed in triplicates from predefined numbers of unstained sections of a standardized tissue size. DNA quantification was done fluorometrically and by qPCR. Up to 40 ng of DNA were analyzed with the QIASeq TMB Panel (incl. MSI primer boosters; Qiagen). Sequencing was done on an Illumina NextSeq platform, TMB scores and MSI status were determined by using the CLC workbench 5.0.1 (Qiagen). Results: Biopsy samples generated less numbers of DNA molecules (as detected by unique molecular identifiers, UMIs) and less overall reads compared to resection samples. UMI coverage was &gt; 500x in all samples with &gt; 15 ng DNA input. TMB scores were highly reproducible among all samples with &gt; 15 ng DNA but differed significantly among samples with limited DNA input. Interestingly, TMB scores were inversely correlated with DNA input among those samples with &lt; 15ng. Thus, valid TMB scores could also be obtained from only one slice of 1 cm 2 tissue from tumor resections or 3 slices of an endoscopic biopsy (each of 5µm thickness). All pre-characterized MSI carcinomas could be detected correctly. Conclusions: We provide first evidence that TMB can be reliably determined also in small biopsies yielding limited DNA content. However, false high TMB scores can occur in samples with &lt; 15ng DNA input. Our results contribute to the definition of minimum requirements (tissue size and DNA input) for valid TMB measurement on clinical FFPE samples.
Delivery of bleomycin among patients with testicular cancer: A population-based study of pulmonary monitoring and toxicity.
Authors: Christopher M. Booth, Michael J. Raphael, Xuejiao Wei, Andrew George Robinson, Philippe L. Bedard, Safiya Karim, M. Dianne Lougheed
Journal: Journal of Clinical Oncology (2019)

e16056 Background: Bleomycin is commonly used to treat testicular cancer and can be associated with severe pulmonary toxicity. There is limited information about how clinicians monitor patients during treatment and the incidence of pulmonary toxicity in routine practice. Methods: The Ontario Cancer Registry was linked to electronic records of treatment to identify all incident cases of testicular cancer treated with orchiectomy and bleomycin, etoposide, and cisplatin (BEP) chemotherapy in the province of Ontario during 2005-2010. Health-administrative databases were used to describe use of pulmonary function tests (PFTs), chest imaging and physician visits. Results: 475 patients were treated with orchiectomy and chemotherapy. Complete chemotherapy records were available for 93% (368/394) of men treated with BEP. Bleomycin was omitted among 32% (116/368) of patients. PFTs were performed in 17% (63/368), 17% (61/368) and 29% (106/368) of patients before BEP, during BEP, and within 2 years of finishing BEP, respectively. During chemotherapy, 62% of patients (227/368) had chest imaging. In the two years following BEP, 23% (85/368) had a physician visit for respiratory symptoms; this rate was substantially higher among men with greater exposure to bleomycin; 40% (24/60) for 10-12 doses bleomycin vs 21% (53/250) for 7-9 doses vs 14% (8/58) for 1-6 doses (p = 0.002). Two percent of men (8/368) had visit codes for pulmonary fibrosis. Conclusions: A substantial proportion of men treated with BEP will seek medical attention after chemotherapy for respiratory symptoms and this is associated with cumulative dose of bleomycin. Use of PFTs and chest imaging during treatment is common. Whether PFT test results or clinical symptoms are leading to bleomycin dose omission is uncertain.
Mutation concordance of matched tissue sample and blood sample: A result of 456 lung cancer patients.
Authors: Xiaoping Wen, He Bin, Ye Lei, Zhang Jing, Lifeng Li, Suo Peisu, Lele Song, Shifu Chen, Chen Jianhua
Journal: Journal of Clinical Oncology (2019)

e20049 Background: Cell-free DNA (cfDNA) sequencing is an important alternative for tissue sequencing when tissue samples are not available. To better study the association of a blood sample and tissue sample, we designed a study to evaluate the concordance of gene mutations of tumor tissues and matched cfDNA. Methods: From May 2017 to January 2019, 456 lung cancer patients were enrolled in this study. For each patient, a matched tumor tissue sample and blood sample were collected. DNA samples were extracted from these samples, and then sequenced with a pan-cancer gene panel. Results: The concordance ratio was computed by the number of common variants divided by the summation of common variants, the number of tissue-specific variants and number of blood-specific variants. Among these 456 patients, an overall by-variant concordance ratio of 49.7% (1457/2932) was observed. When considering only the major driver genes, the observed concordance ratios were EGFR = 45.7% (96/210), KRAS = 48.5% (147/303), ALK-fusion = 50% (8/16) and BRAF = 52.5% (21/40). The mean variant allele frequency (VAF) of common variants was significantly higher than the mean VAF of variants only detected in tissue (29.07% vs. 12.29%, p-value &lt; 2.2e-16). Conclusions: This study shows that the concordance ratio between a tissue sample and a blood sample is close to 50%. As new technologies are being developed to detect low-frequency variants better, we can expect this concordance ratio to improve in the future.