tbuckley/cabot-search huggingface dataset:
Oncologic outcomes of segmentectomy versus lobectomy for radiologically aggressive small-sized lung cancer.
Authors: Atsushi Kamigaichi, Yasuhiro Tsutani, Takahiro Mimae, Yoshihiro Miyata, Kentaro Imai, Hiroyuki Ito, Haruhiko Nakayama, Norihiko Ikeda, Morihito Okada
Journal: Journal of Clinical Oncology (2019)

8525 Background: Despite increasing evidence of favorable outcomes after segmentectomy for indolent lung cancer, such as ground glass opacity-dominant tumors, the adaptation of segmentectomy for radiologically aggressive lung cancer remains controversial. We attempted to elucidate oncologic outcomes after segmentectomy for radiologically aggressive lung cancer. Methods: Data from a multicenter database of 1353 patients with completely resected clinical Stage IA1–IA2 lung cancer at three institutions were retrospectively analyzed to identify radiologically aggressive lung cancer and compare outcomes of segmentectomy versus lobectomy in patients with radiologically aggressive lung cancer using propensity score matching. Results: Multivariable analysis showed that consolidation to maximum tumor (C/T) ratio on preoperative high-resolution computed tomography ( P= 0.037) and maximum standardized uptake value (SUVmax) on 18-fluorodeoxyglucose positron emission tomography/computed tomography ( P= 0.029) were independent predictors of recurrence-free survival (RFS). The criteria for radiologically aggressive lung cancer were determined as C/T ratio ≥ 0.8 or SUVmax ≥ 2.5, for which 522 patients were identified. RFS and overall survival (OS) were significantly worse in patients with aggressive lung cancer (5-year RFS, 83.3%; 5-year OS, 89.4%) than in those without the same (5-year RFS, 97.0%; P&lt; 0.0001; 5-year OS, 97.3%; P&lt; 0.0001). Among patients with aggressive lung cancer, no significant difference in RFS and OS was found between those undergoing lobectomy (n = 392) (5-year RFS, 81.3%; 5-year OS, 88.3%) and segmentectomy (n = 130) (5-year RFS, 90.0%; P= 0.33; 5-year OS, 92.3%; P= 0.76). Among the 111 pairs propensity matched for age, sex, smoking history, solid tumor size, C/T ratio, SUVmax, tumor location, clinical stage, and histology, similar RFS and OS were found between those undergoing lobectomy (5-year RFS, 83.3%; 5-year OS, 88.3%) and segmentectomy (5-year RFS, 90.9%; P= 0.92; 5-year OS, 94.5%). Conclusions: For radiologically aggressive small-sized lung cancer, oncologic outcomes of segmentectomy were equivalent to those of lobectomy.
Evaluation of complete pathological remission rates in surgically resected MSI-high metastatic colorectal cancers (mCRC).
Authors: Kaysia Ludford, Romain Cohen, Wai Chin Foo, Jane V Thomas, Yann Parc, Magali Svrcek, Scott Kopetz, Thierry Andre, Michael J. Overman
Journal: Journal of Clinical Oncology (2019)

e15046 Background: Immune checkpoint inhibition (ICKi) for mCRC with deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) demonstrates a high clinical activity rate that appears durable. The impact of immunotherapy on pathological tumor response in dMMR/MSI-H CRC is unknown. Our aim was to assess the pathological response and clinical outcomes following surgical resection in dMMR/MSI-H CRC patients who undergo surgical resection following immunotherapy. Methods: All dMMR/MSI-H mCRC patients treated with anti-PD1/L1 based ICKi between November 2016 and December 2018 at MD Anderson Cancer Center, Houston, Texas and Saint-Antoine Hospital, Paris, France who then underwent surgical resection were included in this retrospective analysis. MSI-H status was determined by ICH in 4 patients and by PCR and ICH in 8 patients. The primary outcome was pathological response in resected surgical specimens following at least 1 cycle of ICKi. Complete pathological response was defined as the absence of residual cancer cells in the surgical specimen. Results: 12 patients (median age at diagnosis 45 years (range 30-70); 10 germline mutations,2 sporadic) of 111 who received ICKi (11%) underwent surgical resection of primary tumor only (n = 5), metastases only (n = 6) or both primary tumor and metastases (n = 1). 42% of patients received PD1 combined with CTLA4 iCKi while 58% received PD1 monotherapy. The median time from ICKi introduction to surgery was 12 months (range 2-28). Prior to surgery 1 patient had complete radiographic response while 11 patients had residual tumor on imaging. 9 surgeries were done with curative intent and 3 with palliative intent. 11 patients achieved pCR while 1 achieved near pCR with rare viable tumor remaining (prior ICKi duration was 2 months). Median follow-up from surgery is 7 months. No patients have progressed following surgical resection. Conclusions: Complete pathological response is achievable with ICKi for dMMR/MSI-H mCRC. For these patients this data supports the curative potential of anti-PD1 based therapy and suggests that residual radiographic tumor may not require surgical resection following response to anti-PD1 based therapy.
Serum microRNA signatures for the detection of pancreatobiliary cancer.
Authors: Shuichi Mitsunaga, Shogo Nomura, Kazuo Hara, Yukiko Takayama, Makoto Ueno, Keiji Hanada, Ikuya Miki, Shinichiro Takahashi, Takamichi Kuwahara, Tomohiro Nomoto, Tamotsu Sudo, Akira Myomoto, Hiroko Sudo, Satoko Takizawa, Motohiro Kojima
Journal: Journal of Clinical Oncology (2019)

e15718 Background: The diagnostic value of serum microRNAs (miRNA) in a highly sensitive microarray for pancreatobiliary cancer (PBca) has been demonstrated. This study attempted to build and validate a signature comprised of multiple serum miRNA markers for discriminating PBca from healthy controls. Methods: A multicenter prospective study on the diagnostic performance of serum miRNAs was conducted. The patients (pts) with treatment-naïve PBca and healthy participants aged ≥60 years were enrolled. Clinical data and sera were collected. Target population was randomly divided to training or validation cohort with an allocation ratio of 2:1. Twenty-nine serum miRNA markers on the microarray data were analyzed. Using any combinations of the markers, a Fisher’s linear discriminant analysis was performed, and the resulting sensitivity, specificity and AUC of ROC curve to discriminate PBca from healthy controls were calculated for each combination. Marker combinations with a sensitivity/specificity (SN/SP) of ≥80%/90% and high AUC in comparison with AUC of CA19-9 were defined as the diagnostic miRNA signature, which were selected in the training cohort. Next, the signatures were screened out which showed a good reproducibility in the validation cohort. As an independent external cohort, PBca pts and healthy with pooled frozen sera were enrolled and the identified miRNA signatures were further validated. Results: Total of 546 participants (80 healthy and 223 PBca in training set, 40 healthy and 104 PBca in validation set, 49 healthy and 50 PBca in external validation set) were analyzed in this study. Four serum miRNA combinations were identified as the diagnostic miRNA signature. In the training set, four miRNA signatures, consisted of 10 miRNAs, were developed. For the best-performed miRNA signature, the SN/SP and AUC in the validation and external validation cohorts were 84/90% and 0.95 (CA19-9: 73/95% and 0.88) and 84/90% and 0.93 (CA19-9: 80/94% and 0.87), respectively. Conclusions: The diagnostic serum miRNA signatures for PBca were identified in this study.
Prognostic significance of the number of pelvic lymph-nodes resection in patients with cervical adenocarcinoma: An analysis from JGOG 1070S study.
Authors: Yuji Ikeda, Tsunekazu Kita, Akiko Furusawa, Munetaka Takekuma, Mikio Mikami
Journal: Journal of Clinical Oncology (2019)

5529 Background: Although resection of more than 20 lymph-nodes is considered to be adequate in pelvic lymphadenectomy for cervical cancer patients, prognostic significance of the number of resected lymph-nodes (PLN-num) is clinically still unknown. Methods: This nationwide multicenter retrospective study (JGOG 1070S) examined consecutive 693 patients with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy including pelvic and/or para-aortic lymphadenectomy between 2008-2009 at 87 institutions of the Japanese Gynecologic Oncology Group. Maximum number of enrollments from one institution was limited 10 or less to minimize the inter-institutional bias. Correlation between PLN-num and prognosis was analyzed using Cox hazard model with considering histological subtypes. Results: Of 473 eligible cases in this study, the average PLN-num per a case in each institution was positively correlated with the number of total cases treated in each institution per year. (R = 0.42, P = 0.012). Patients with high PLN-num showed favorable progression free survival (PFS) (P = 0.12). Focusing on adeno and adeno-squamous carcinomas, significantly improved PFS was shown in high PLN-num cases (P = 0.012), although no significance was found in squamous cell carcinoma (P = 0.754). Multivariate analysis in adeno and adeno-squamous cases showed PLN-num as an independent prognostic factor (HR; 0.46, 95%CI; 0.24–0.84, P = 0.026) along with disease stage and adjuvant therapeutics. Subset analysis of adeno and adeno-squamous cases without adjuvant therapeutics showed significant improvement of survival in high PLN-num group (P = 0.019). Conclusions: In our study, PLN-num in lymphadenectomy for patients with cervical adeno or adeno-squamous carcinoma was clarified to be a significant prognostic factor. Systematic total lymphadenectomy is recommended for these patients to obtain a favorable prognosis.
Erratum: Synovial tissue research: a state-of-the-art review
Authors: Carl Orr, Elsa Vieira-Sousa, David L. Boyle, Maya H. Buch, Christopher D. Buckley, Juan D. Cañete, Anca I. Catrina, Ernest H. S. Choy, Paul Emery, Ursula Fearon, Andrew Filer, Danielle Gerlag, Frances Humby, John D. Isaacs, Søren A. Just, Bernard R. Lauwerys, Benoit Le Goff, Antonio Manzo, Trudy McGarry, Iain B. McInnes, Aurélie Najm, Constantino Pitzalis, Arthur Pratt, Malcolm Smith, Paul P. Tak, Sander W. Tas, Rogier Thurlings, João E. Fonseca, Douglas J. Veale
Journal: Nature Reviews Rheumatology (2017)
Phase 1b study of chemoprevention with green tea polyphenon E (PPE) and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (Erlotinib) in patients (pts) with advanced premalignant (AP) lesions of the head and neck.
Authors: Dong Moon Shin, Jonathan Jay Beitler, Mark El-Deiry, Conor Ernst Steuer, Amy Y. Chen, Harry Micael Baddour, Zhuo Georgia Chen, Steve Roser, Kelly R. Magliocca, Mihir Patel, Christopher C Griffith, Adam Klein, Taofeek Kunle Owonikoko, Fadlo Khuri, Sreenivas Nannapaneni, Nabil F. Saba
Journal: Journal of Clinical Oncology (2019)

6049 Background: Based on the strong synergistic effects between green tea polyphenon E (PPE) and EGFR-TKI in our preclinical studies (Int J Cancer, 2008; Cancer Prev Res, 2009; JCO, 2009), we conducted a phase 1b study with PPE and erlotinib combination for APL (mild-, moderate-, severe-dysplasia or carcinoma in situ [CIS]) of the oral cavity and larynx from 2/2011 to 11/2017 at Emory Winship Cancer Institute. Methods: All pts were enrolled after signing the IRB approved Informed Consent Form. Tissue biopsy before and at 6-months (6-M) treatment was mandatory, and cytobrushed samples of the APL and normal buccal mucosa at 3-, 6-, and 12-M were obtained for biomarker studies. Treatment included fixed dose of PPE (200 mg, P.O.,TID) and dose escalation of erlotinib P.O., (50mg [level 1], 75mg [level 2] and 100mg [level 3]) for 6-M. The primary endpoint was safety and toxicity, and secondary endpoints were evaluation of pathologic responses, cancer free survival (CFS) and biomarker modulation. Results: Out of 27 enrolled pts, 6 control subjects for biomarker studies, 2 ineligible, and 19 were treated with PPE and erlotinib for 6-M. Clinical characteristics of treated patients included median age, 63 yrs. (range,33-78); 9 M/10 F; 10 former or current smokers/9 never smokers; 15 severe dysplasia or CIS, 2 moderate dysplasia, 2 mild dysplasia; 13 had surgical resection; 17 oral cavity primary; and 2 at larynx. 3 pts were treated at dose level 1, 4 at level 2, and 12 at level 3. Toxicity (G0 or G1 excluded) were: skin rash (1 G3, 1 G2), pruritus/dry skin (1 G2), fatigue (1 G2), diarrhea (1 G2), epistaxis (1 G2), and hypertension (2 G3, 1 G2). Skin rash (associated with erlotinib) may be DLT and MTD has not been reached. The recommend doses for phase 2 or 3 studies will be PPE 200mg TID plus erlotinib 100mg QD. 17 pts were assessed for pathologic responses at 6-M: pCR 7/17 (41%), pPR 2/17 (12%), pSD 5/17 (29%) and pPD (3/17 (18%). The median follow up was 32 months. Median CFS has not been reached. 16 pts are alive at the time of data analyses and 1 pt died (by noncancerous reason). Biomarker studies are ongoing for tissues and/or cytobrushed samples. Conclusions: The treatment of the combination of green tea PPE plus erlotinib for 6-M was well tolerated in pts with APL of the head and neck, and showed significant pathologic response rates (pCR and pPR, 53%). This combination therefore deserves further investigation for efficacy testing. Clinical trial information: NCT01116336.
Innovative Practice in Latin America: Medical Tourism and the Crowding Out of Research
Authors: Felicitas Holzer, Ignacio Mastroleo
Journal: The American Journal of Bioethics (2019)

In an insightful article recently published in the American Journal of Bioethics, Jacob Earl outlines the concept of innovative practice, addresses ethical problems and presents a permissive oversight proposal to deal with the ethical concerns identified.We agree to a large extent with Earl's approach and, therefore, decided to develop his comprehensive analysis further.In particular, we want to extend it from national to global contexts.In this regard we argue that innovative practice in countries with poor regulation of the sale and marketing of new drugs carries a higher risk of crowding out research.In turn, this entails the potential harm to global public health caused by a significant reduction or exclusion of sound and socially valuable research.We think that analyzing innovative practices performed in a global landscape of poor regulation, like the one we find in many Latin American countries, can provide us with useful insights into Earl's approach.
Population-based screening for <i>BRAF</i> V600E in metastatic colorectal cancer (mCRC) to reveal true prognosis.
Authors: Jenny E. Chu, Benny Johnson, Van K. Morris, Kanwal Pratap Singh Raghav, Lucas Swanson, Howard John Lim, Daniel John Renouf, Sharlene Gill, Robert Wolber, Aly Karsan, David F. Schaeffer, Scott Kopetz, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2019)

3579 Background: BRAFV600E ( BRAF) mutations (mts) portend poor prognosis in mCRC and patients (pts) may die before ascertainment. Since 2014, Vancouver Coastal Health (VCH) has performed reflex hereditary screening of CRCs with BRAF and mismatch repair (MMR) immunohistochemistry (IHC). We evaluated this BRAF mt population-based cohort ( BRAF POP ) to establish the true prognosis of BRAF mts in mCRC. Methods: We reviewed all mCRCs from VCH between 4/2014 and 5/2018 for BRAF by IHC (VE1 antibody). Overall survival (OS) from stage IV diagnosis was compared to mCRCs with next generation sequencing (NGS) determined BRAF mts ( BRAF NGS ) from BC Cancer &amp; MD Anderson. BRAF NGS OS did not differ by center (p = 0.77). Results: See table for BRAF cohort baseline characteristic comparison. BRAF POP pts had worse OS than BRAF NGS pts (HR 2.5, 95% CI 1.6 – 3.9, P &lt; 0.0001). Median OS for all BRAF mt pts was 17.9 mos. Both groups had worse OS than wild type pts (P &lt; 0.0001). 52 (81%) of BRAF POP pts were referred to oncology, 40 (63%) received chemotherapy, and 12 (19%) had NGS BRAF testing. BRAF POP pts who had NGS testing with BRAF mts had OS comparable to other BRAF NGS pts (P = 0.89) and better OS than BRAF POP pts that never had NGS testing (HR 0.37, 95% CI 0.18-0.76, P = 0.030). Pts with BRAF mts and MMR deficiency (dMMR) (n = 40) had worse OS than MMR proficiency (pMMR, n = 202) (1.6, 95% CI 1.0-2.5, P = 0.011). This was driven by BRAF POP dMMR pts (HR 1.9, 95% CI 0.9-4.0, P = 0.036) as no difference was seen by MMR in BRAF NGS pts (HR 1.3, 95% CI 0.8-2.2, P = 0.30). Conclusions: Current estimates of prognosis for mCRC with BRAF mts likely underestimate its impact due to referral bias for NGS testing. BRAF mts with dMMR are associated with worse prognosis than pMMR. This appears driven by BRAF POP pts. [Table: see text]
Albumin levels and Prognostic Nutritional Index in glioblastoma.
Authors: Anas Saeed Bamashmos, Addison Barnett, Assad Ali, Hong Li, Lilyana Angelov, Gene H. Barnett, Alireza Mohammad Mohammadi, Samuel T. Chao, Jennifer S. Yu, Erin Sennett Murphy, John H. Suh, Glen Stevens, David M. Peereboom, Manmeet Singh Ahluwalia, Wei (Auston) Wei
Journal: Journal of Clinical Oncology (2019)

e13567 Background: Albumin levels are widely used to estimate patients’ nutritional status. Low perioperative albumin levels are associated with worse outcomes. Moreover, Prognostic Nutritional Index (PNI), which is calculated from serum albumin levels and peripheral blood lymphocyte count as follows: PNI = (Albumin x 10) + (0.005 x ALC), has been used to predict both short and long term outcomes in patients with wide variety of tumors. The primary objective of this study was to characterize perioperative albumin levels and PNI in newly diagnosed GBM patients. Secondary objectives included associations between albumin levels and PNI on progression free survival (PFS) and overall survival (OS). Methods: We retrospectively reviewed 568 newly diagnosed GBM patients who underwent surgery followed by standard of care chemoradiation. We analyzed the association between albumin and PNI on age, sex, MGMT methylation status, and extent of surgical resection on PFS and OS using a multivariate Cox proportional hazard model. Results: Of the 568 patients collected, 355 (62.5%) were males, 158 (27.8%) had gross total resection of the tumor, and 197(42.5%) were MGMT methylated. Both albumin and PNI were associated with OS but not PFS. The hazard ratio (HR) for OS among the top 2 quartiles of both albumin level and PNI were significantly higher than the bottom two quartiles. The median albumin level was 4.0 and the median PNI was 40. The point for significant high hazard ratio (HR) was around median value for both Albumin and PNI based on restricted cubic spine Cox regression models. The Kaplan-Meir (KM) estimated median OS was 15.2 months for albumin &gt; 4, and 7.6 for albumin ≤4. The KM estimated median OS was 14.6 months for PNI &gt; 40, and 5.7 for PNI≤40 (P logrank &lt; 0.001 for both). While controlling for other factors that may also be associated with early death including age, gender, surgery type and MGMT status, HR = 1.9 (95% CI = 1.4- = 2.6) for Albumin &lt; 4, and HR = 2.1 (95% CI = 1.5- 3.0) for PNI &lt; 40 compared to their counterpart. Conclusions: Glioblastoma patients with perioperative albumin &gt; 4 had a median OS of 15.2 months and 7.6 months for albumin ≤4, and a median OS of 14.6 months for PNI &gt; 40 and 5.7 months for PNI≤40 (P logrank &lt; 0.001 for both).
Neoadjuvant pembrolizumab (Pembro) for early stage non-small cell lung cancer (NSCLC): Updated report of a phase I study, MK3475-223.
Authors: Jair Bar, Damien Urban, Efrat Ofek, Aliza Ackerstein, Ilanit Redinsky, Nir Golan, Iris Kamer, David Simansky, Amir Onn, Stephen Raskin, Tiberiu Shulimzon, Michael Peled, Nona Zeitlin, Sharon Halparin, Menucha Jurkowicz, Ramez Abukhalil, Marina Perelman, Alon Ben-Nun
Journal: Journal of Clinical Oncology (2019)

8534 Background: Resected NSCLC clinical stage I or II harbor a 5 year survival of only 30-50%. Immunotherapy might be more effective in low-burden disease. We hypothesized that neo-adjuvant immunotherapy is a feasible, safe and effective treatment (Tx) for early stage NSCLC. Methods: MK3475-223 is an ongoing phase I study of neoadjuvant pembrolizumab in stage I-II NSCLC. All Pembro Txs are 200mg q 3 weeks (wks). Objectives: determine safety; recommended phase 2 dose/schedule; pathological &amp; radiological response. Doses-schedule limiting toxicities (DLT) were defined as significant surgical complications (bleeding, delayed wound healing, ARDS, prolonged air-leak) or a significant delay of surgery. The doses-schedule escalation cohorts were (i) single pembro dose 3 wk prior to surgery; (ii) 2 pembro doses, 2 wks later surgery; (iii) 2 pembro doses, 1 wk later surgery. Expansion cohort received the doses-schedule of cohort (iii). Percentages of remaining viable tumor in the post-Tx were assessed, 10% or less was considered amajor pathological response (MPR). IHC for pre-Tx PDL1 was done. Efficacy was evaluated for the patients who had received 2 doses of pembrolizumab. Results: No DLT occurred in the dose-schedule escalation cohorts. 10 patients received 2 cycles of neo-adjuvant pembrolizumab. 4 patients achieved a MPR (4/10 who received 2 cycles of pembro; 40%; 95% C.I. 16.7-68.8%). No correlation is seen between the levels of PDL1 pre-Tx and the pathologic response. Size of the tumor and N status was also not in any apparent correlation with MPR (data not shown). Interestingly, all of the MPR cases had a relatively long interval from 1 st Tx till surgery. Clinical trial information: NCT02938624. Conclusions: Neo-adjuvant pembro is safe and feasible. A promising sign of efficacy is seen. Achieving MPR might require a longer 1 st -Tx-surgery interval. Predictive biomarkers for response might be different from those in advanced disease. Recruitment and correlative studies are ongoing.[Table: see text]