tbuckley/cabot-search huggingface dataset:
Outcomes of myeloablative, T cell deplete unrelated donor hematopoietic stem cell transplantation at a single center.
Authors: Mahmoud Gaballa, Albert Jang, Hussein Hamad, Shaun Bulsara, Meng-Fen Wu, George Carrum, Carlos Almeida Ramos, Rammurti Kamble, LaQuisa Hill, Sai Ravi Pingali, Ngoc Vu, Audrey Scholoff, Gloria Obi, Helen E. Heslop, Premal D. Lulla
Journal: Journal of Clinical Oncology (2020)

e19525 Background: Myeloablative conditioning (MAC) and unrelated donor (UD) hematopoietic cell transplantation (HCT) are associated with increased non-relapse mortality (NRM) compared with matched related donor (MRD) HCT [18%, 21%, and 32% for MRD, Matched UD (MUD), and mismatched MUD (MMUD), respectively, p &lt; 0.001] (Saber et al, 2012). Our center uses alemtuzumab as means of T cell depletion to mitigate NRM risk in UD HCT. Here, we report outcomes utilizing this strategy. Methods: We retrospectively analyzed adult patients (pts) who received alemtuzumab-based T cell deplete MAC UD HCT from August 2012 to December 2017. Outcomes were estimated via Kaplan Meier and cumulative incidence methods. Results: Sixty-eight pts underwent T cell deplete MAC UD HCT for AML/MDS (n = 32), ALL (n = 18), lymphoma (n = 5), and other diseases (n = 13). Thirty-nine (57.4%) underwent a MUD HCT, while 29 (42.4%) underwent a MMUD (≤ 9/10 match) HCT. Median follow up was 35.5 months (m) (range 1.5 – 71.1). Median age was 46 years (range 21 - 68), 58.8% were male. Nineteen AML pts (67.9% of all AML) were considered high risk defined as secondary AML (n = 3), CR2 or more (n = 9), primary induction failure (n = 6) or having gross residual disease at time of HCT (n = 1). At 24 m, overall survival (OS) for the entire cohort was 65.3% (95%CI (CI) 53.5%- 77.2%), GVHD relapse-free survival (GRFS) was 54.8% (CI 42.8%- 66.9%), NRM was 10.4% (CI 4.5%- 19.2%), and relapse incidence (RI) was 27.3% (CI 17.1%- 38.5%). None of the 68 pts had graft failure or rejection. In the AML/MDS cohort, at 24 m OS was 52.3% (CI 33.9%- 70.7%), GRFS was 41.4% (CI 23.9%- 59%), NRM was 9.7% (CI 2.4%- 23.2%), and RI was 39.1% (CI 21.8%- 56.2%). Non-AML/MDS pts at 24 m had OS, GRFS, NRM and RI of 76.8% (CI 62.6%- 90.9%), 66.7% (CI 51.3%- 82.08%), 11.1% (CI 3.4%- 23.9%), and 16.7% (CI 6.6%- 30.6%), respectively. The table summarizes our outcomes. Conclusions: We show that alemtuzumab-based MAC conditioning for UD HCT has the benefit of being well tolerated with low NRM and high GRFS, while having comparable RI and OS compared to published outcomes of T cell replete MAC UD HCT (Saber et al, 2012). However, the retrospective nature without a comparator is a major limitation which necessitates a future prospective study to validate these findings. [Table: see text]
老年社区获得性肺炎治疗反应性及预后的评估
Authors: 王毅, 刘均宾, 谢绪峰
Journal: BMJ (2012)

分析124例老年社区获得性肺炎患者的临床资料,发现C反应蛋白、乳酸、肺炎严重度指数和CURB-65评分与患者治疗反应、病情变化及预后有明显相关性.提示监测以上指标对评估老年社区获得性肺炎患者的治疗反应和预后有重要的临床意义。
Clinical and imaging characteristics of reversible posterior encephalopathy syndrome in 8 patients
Authors: Yu-ping Xing, Yu-fen Wang
Journal: BMJ (2009)

A retrospective study was conducted in 8 patients with reversible posterior encephalopathy syndrome to analyze the clinical and MRI findings and follow-up outcomes of the disease.The participants clinically presented with elevated blood pressure(n=8),blurred vision(n=6),severe headache(n=4),dysphofia(n=4),impaired shon-term memory(n=2),and seizure(n=6).The most important imaging finding Was vasogenic edema,which showed better prognosis.

Key words: 
Brain diseases;  Magnetic resonance imaging
Equivalence randomized trial comparing treatment based on sentinel node biopsy versus neck dissection in operable T1-T2N0 oral and oropharyngeal cancer.
Authors: Renaud Garrel, Françoise Perriard, Valentin Favier, Fanny Richard, Jean Pierre Daures, Marie De Boutray
Journal: Journal of Clinical Oncology (2020)

6501 Background: Although sentinel node (SN) biopsy is known to be accurate in operable oral and oropharyngeal cT1-T2N0 squamous cell carcinomas (OC), the oncological equivalence of a treatment based on SN compared to that based on neck dissection (ND) has to be evaluated. Methods: A prospective multicenter randomized medico economic study included patients with OC operated of primary tumor and systematic neck dissection in ND-arm (standard treatment) versus patients operated of primary tumor and SN biopsy only if negative or ND if SN biopsy positive (SN-arm, experimental treatment). Primary endpoint was neck-relapse-free survival at 2 years and 5 years. Hypothesis of equivalence was tested with a delta of 10%. Functional outcomes were assessed by comparing the length of the hospital stay, the number of physiotherapy prescriptions and dysfunctions in neck and shoulder scales during the 2 post-operative years. Results: Out of 307 included patients in 10 hospital centers, 279 evaluable cases showed a neck-relapse-free survival at 2 years and 5 years respectively of 89,6% (95%CI: 0.827; 0.938) and 89,6 %, (95%CI: 0.827; 0.938) in the ND-arm (14 neck relapses out of 139 patients) and of 90,7% (95%CI: 0.842; 0.946) and 89,4% (95%CI: 0.823; 0.938) in the SN-arm (13 neck relapses out of 140 patients). The survival difference between the two arms was less than the 10% expected interval, confirming the equivalence with p = 0.008. The median length of hospital stay was 7 days (ext. 3-30) in SN-arm and 8 days (ext. 2-94) in ND-arm (Wilcoxon’s test, p = 0.001). The other functional outcomes were statistically worse in the ND-arm at the 2nd, 4th and 6th postoperative months. There was no more difference at 12 months and later. Conclusions: This study demonstrated the oncological equivalence of the SN approach compared to the ND approach in a multicenter study with a lower morbidity and care consumption in the SN approach during the 6 first post-operative months. Treatment based on sentinel node biopsy is established as a standard of care in OC. Clinical trial information: NCT02855723 .
Flexible Mixture Model Approaches That Accommodate Footprint Size Variability for Robust Detection of Balancing Selection
Authors: Xiaoheng Cheng, Michael DeGiorgio
Journal: Molecular Biology and Evolution (2020)

Long-term balancing selection typically leaves narrow footprints of increased genetic diversity, and therefore most detection approaches only achieve optimal performances when sufficiently small genomic regions (i.e., windows) are examined. Such methods are sensitive to window sizes and suffer substantial losses in power when windows are large. Here, we employ mixture models to construct a set of five composite likelihood ratio test statistics, which we collectively term B statistics. These statistics are agnostic to window sizes and can operate on diverse forms of input data. Through simulations, we show that they exhibit comparable power to the best-performing current methods, and retain substantially high power regardless of window sizes. They also display considerable robustness to high mutation rates and uneven recombination landscapes, as well as an array of other common confounding scenarios. Moreover, we applied a specific version of the B statistics, termed B2, to a human population-genomic data set and recovered many top candidates from prior studies, including the then-uncharacterized STPG2 and CCDC169-SOHLH2, both of which are related to gamete functions. We further applied B2 on a bonobo population-genomic data set. In addition to the MHC-DQ genes, we uncovered several novel candidate genes, such as KLRD1, involved in viral defense, and SCN9A, associated with pain perception. Finally, we show that our methods can be extended to account for multiallelic balancing selection and integrated the set of statistics into open-source software named BalLeRMix for future applications by the scientific community.
The short-term health and economic burden of gestational diabetes mellitus in China: a modelling study
Authors: 徐婷婷, Dainelli Livia, 余恺, 马良坤, Zolezzi Irma Silva, Detzel Patrick, 方海
Journal: BMJ (2018)

目的
妊娠期糖尿病（GDM）属于高危妊娠，与母婴不良妊娠结局的发生密切相关。本研究目的是评估2015年中国的GDM的短期健康与经济总体负担。


方法
研究运用TREEAGE PRO软件，建立决策树模型，评估由GDM造成的增量疾病成本和孕妇生命质量损失[质量调整生命年（QALY）]。研究设定的跨度为孕妇怀孕第28周至分娩结束。模型中所用概率数据和成本数据来源于当前的文献综述、临床诊断治疗指南、样本省份医疗价格指南和专家访谈资料。并对关键概率和成本变量进行敏感性分析。


研究对象
2015年处于妊娠期的中国女性。


结果
每个GDM患者的平均医疗成本为6 677.37元（相当于2015年1 929.87美元），比健康孕妇高出95%。其中：GDM的诊断和治疗费用为4 421.49元；母亲的并发症治疗费用为1 340.94元，比健康孕妇高出26%；新生儿并发症治疗费用为914.94元，比健康孕妇组的新生儿高出52%。2015年，中国有1 650万的婴儿出生，按照GDM患病率为17.5%，GDM的患者人数为290万人。据此估计GDM造成的年度总体社会经济负担为193.6亿元（相当于55.9亿美元）。而健康质量损失估计约为260 000 QALY。


结论
即使是从短期来看，GDM仍为中国带来了巨大的健康与经济负担，需要社会更多的关注。同时我们的研究结果也表明，有必要从国家层面上来实施GDM预防和治疗策略，以减少社会和个人的经济和健康负担。
心肌梗死院前溶栓的有效性和安全性观察
Authors: 谢圣兰, 向小平, 刘枫, 周喆, 董蕾, 胡大一, 孙利红
Journal: BMJ (2004)

130例AMI患者中院前组76例,院内组54例,发病至开始溶栓时间均≤12 h.所有患者均嚼服阿司匹林300 mg,并予尿激酶100万单位+20 ml生理盐水于10 min内静脉推注,再予150万单位+100 ml生理盐水中于60 min内静脉滴注.院前组比院内组溶栓时间平均提前1.4 h;临床开通率在院前组为76%,院内组为63%;随访5周发现反复心绞痛发作、重度心律失常和心脏性死亡的发生在院前组明显少于院内组。
Radioiodine (RAI) in combination with durvalumab for recurrent/metastatic thyroid cancers.
Authors: Bharat Burman, Eric Jeffrey Sherman, Anuja Kriplani, Loren S. Michel, Lara Dunn, James Vincent Fetten, Elizabeth Warner, Ravinder K Grewal, Mona Sabra, R. Michael Tuttle, Laura Boucai, Stephanie Fish, Sofia Haque, Irina Ostrovnaya, Ronald A Ghossein, Jeffrey Knauf, David G. Pfister, James A Fagin, Alan Loh Ho
Journal: Journal of Clinical Oncology (2020)

6587 Background: Immune checkpoint blockade (ICB) has limited efficacy for radioiodine-refractory thyroid cancer. The high incidence of autoimmune thyroid disease and ICB-induced hypothyroidism suggests that loss of T cell tolerance to thyroid protein epitopes is common and can be activated by ICB to induce immune responses. We hypothesize that RAI can enhance presentation of thyroid protein immunogens and putative neoantigens in thyroid cancers to amplify the effectiveness of ICB. We studied the safety and efficacy of RAI plus the anti-PD-L1 agent durvalumab (durva) in recurrent/metastatic (R/M) patients (pts). Methods: Pts. had at least one RAI-avid tumor on the most recent RAI scan or one tumor on FDG PET with an SUVmax &lt; 10. RECIST measurable disease was required. Any number of prior therapies was allowed. Pts were treated with durva 1500 mg IV every 4 weeks with recombinant human TSH (rhTSH)-stimulated RAI (100 mCi) administered in Cycle 1. Treatment beyond progression was allowed. The primary objective was to assess safety. Durva related dose limiting toxicities (DLTs) were monitored for 6 weeks after the first dose. Since no durva DLTs were observed in the first 6 pts, per protocol rules the trial accrued 11 pts total. Secondary objectives were assessing best overall response (BOR) per RECIST and progression-free survival (PFS). Results: 11 pts (7 female) were enrolled. Eight had prior drug therapy. No DLTs or &gt; Grade 3 durva related adverse events (AEs) were observed. The most common non-laboratory AEs (regardless of attribution) were cough (7), hypertension (7), pain (6), edema (5), and fatigue/nausea/diarrhea/arthralgia/dry skin/dyspnea/edema (4 each). As of 2/6/20, 2 had partial response, 7 stable disease, and 2 progression of disease as BOR. Six pts had tumor regression. Four pts received treatment for &gt; 6 months. Six are still on treatment. Analyses of research biopsies (bxs) (8 had pre-treatment bxs, 6 had an additional on-treatment bx) will be presented. Conclusions: Durva plus RAI is safe and well tolerated. The preliminary efficacy signal in this small cohort is promising. Understanding how RAI plus PD-L1 targeting impacts the tumor immune microenvironment may guide how RAI should be evaluated in future ICB trials. Clinical trial information: NCT03215095 .
Peritoneal mesotheliomas characterized by less cell-cycle alterations and more <i>TRAF7</i> alterations than malignant pleural mesotheliomas.
Authors: Michael Offin, Jacklynn V. Egger, Andrea Cercek, Garrett Michael Nash, Marc Ladanyi, Marjorie Glass Zauderer
Journal: Journal of Clinical Oncology (2020)

9059 Background: While peritoneal mesotheliomas (PM) are clinically distinct from malignant pleural mesotheliomas (MPM) it is unknown if genetic alterations reflect these differences. Here we report the molecular alterations and clinicopathologic characteristics of a prospectively collected PM cohort as compared to MPM. Methods: Patients with PM (n = 59) and targeted next generation sequencing (NGS; MSK-IMPACT) from January 2014 to January 2019 were assessed and followed through February 2020. Germline variants were analyzed in consented patients. NGS was compared to patients with MPM (n = 194) assessed in the same time interval. Results: Median age at diagnosis was 61 (range: 20-77), 56% were women (n = 33), and 92% had epithelioid histology (n = 54). 66% had ascites (n = 39) and 24% developed extra-abdominal metastases (n = 14; including lung, pleura, and mediastinum). 68% (n = 40) underwent surgical debulking and 80% (n = 47) had infusional therapy (median lines: 3) including platinum/pemetrexed (n = 38), EPIC (n = 22), HIPEC (n = 15), and immunotherapy (n = 16). The median overall survival (OS) from diagnosis was 5.4 years (median follow up 3.5 years). The median tumor mutation burden (TMB) was 1.8 mut/Mb (range: 0-14.9) in PM vs 2.0 mut/Mb (range: 0-31.5) in MPM (p = 0.049). More patients with PM had TRAF7 alterations than in MPM (5/59 vs 3/194; p = 0.02) while fewer had CDKN2A/ CDKN2B (4 vs 55; p = 0.0004). All patients with TRAF7 altered PM had well-differentiated papillary epithelioid histology. There was no difference in the prevalence of other common alterations such as BAP1 (32 vs 98; p = 0.66), NF2 (12 vs 55, p = 0.24), SETD2 (11 vs 24; p = 0.28), and TP53 (9 vs 28; p = 0.84) in PM vs MPM respectively. Patients with BAP1-altered PM had shorter OS (4.6 vs 9.8 years; HR 2.6, 95% CI 1.1-6.4; p = 0.04) while TRAF7-altered PM had improved OS (not reached vs 4.8 years; HR 0.3, 95% CI 0.1-0.9; p = 0.04) compared to wild type. 13% (4/30) of patients with PM had pathogenic variants on germline NGS ( POT1 I78T, MUTYH R109Y, BAP1 E402*, APC I1037K). Conclusions: NGS confirms the distinct biology of PM compared to MPM. Specifically, the former shows fewer cell cycle ( CDKN2) alterations compared to MPM. In contrast to MPM, BAP1 alteration was associated with shorter survival. As previously described, we found enrichment of TRAF7 in well differentiated papillary epithelioid PM associated with improved survival but notably some TRAF7 alterations were identified in poorly differentiated MPM. Consistent with other reports, the prevalence of germline alterations was 13%.
Is hypofractionated radiation associated with improved timely completion of adjuvant radiation in breast conserving therapy? A National Cancer Database study.
Authors: Steven Gerard Woodward, Brandon George, Karan Varshney, Alliric Isaac Willis
Journal: Journal of Clinical Oncology (2020)

539 Background: Timely completion (TC) of adjuvant radiation therapy following breast conservation therapy (BCT) has been associated with improved mortality and disease-free survival (DFS). Little data exists comparing TC of hypofractionated radiation (HR) and traditional radiation (TR). Methods: We performed a retrospective review of the National Cancer Data Base (2012-2016) on patients undergoing BCT. A multivariable logistic regression model was used to compare TC of HR (within 5 weeks of initiation) and TR (within 7 weeks of initiation) with interaction terms to look at within treatment effects of patient, tumor, and facility characteristics. Results: A total of 360,834 patients who underwent BCT were identified with 65% (n=235,783) undergoing TR and 35% (n=125,051) undergoing HR. TC of HR was achieved in 93.5% of patients and 74.2% of TR patients (p&lt;0.0001). Across categories of year of diagnosis, age, race, median income, facility type, distance to treatment, T-stage, chemotherapy use, and lymph node status it was found that rate of TC was greater in HR compared to TR. The effect on TC by these factors was different in HR patients compared to TR in all categories except median income, distance to treatment, and T-stage (table). Conclusions: The decision between use of HR or TR in BCT is an essential component in treatment of breast cancer patients. Providers may improve mortality and DFS by identifying patients who are more likely to finish HR or TR on time based on patient, facility, and tumor factors. [Table: see text]
Osimertinib in previously EGFR-TKI treated non-small cell lung cancer (NSCLC) patients without T790M mutation: Real-world evidence.
Authors: Yung-Hung Luo, Han Liu, Jason A. Wampfler, Henry D. Tazelaar, Yalun Li, Tobias Peikert, Dan Liu, Konstantinos Leventakos, Yuh-Min Chen, Yanan Yang, Shih-Hwa Chiou, Ping Yang
Journal: Journal of Clinical Oncology (2020)

e21631 Background: The efficacy of osimertinib in previously EGFR-TKI treated NSCLC patients without T790M mutation remains unclear in real-world practice. We investigated whether osimertinib can provide survival benefit in EGFR-mutant patients without T790M mutation after 1st/2nd generation TKI treatment. Methods: Between January 1, 2009, and March 31, 2019, 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as≥2 nd -line EGFR-TKI treatment were identified at Mayo Clinic. The time to treatment failure of osimertinib was analyzed by the Kaplan-Meier (KM) estimates. The risk of death post diagnosis was analyzed by Cox proportional hazard models. Results: Among 417 EGFR-mutant patients, higher risk of death was found in patients with age above 65 years, non-adenocarcinoma, no surgery treatment, no radiation treatment, non-exon 19 deletion/exon 21 L858R mutation, higher ECOG PS (2-4), PD-L1 expression of 50% or more, bone metastasis, live metastasis, and adrenal metastasis (all p &lt; 0.05). Moreover, osimertinib as ≥2nd-line TKI treatment in patients with or without T790M revealed lower risk of death compared to 1 st /2 nd generation TKI treatment without subsequent osimertinib (HR = 0.33; 0.46, and p = 0.0002; 0.0232, respectively). However, among patients receiving osimertinib as ≥2 nd -line TKI treatment, patients with T790M did not have superior survival than those without (p = 0.2803). Among 154 patients receiving osimertinib, a higher risk of treatment failure for osimertinib was found in male (HR = 1.72; p = 0.0327), patients with 1 st -line TKI duration ≤12 months (HR = 2.16; p = 0.0019), BMI drop &gt; 10% (HR = 1.85; p = 0.0207), PD-L1 levels of 50% or more (HR = 4.28; p = 0.0008), and 1 st -line TKI with afatinib (HR = 2.19; p = 0.0136). Nonetheless, osimertinib as ≥2nd-line TKI in patients without 790M mutation did not have higher risk of treatment failure than those with T790M (p = 0.1236). Conclusions: This is the first study to demonstrate that osimertinib can provide similar survival benefit in previously EGFR-TKI treated NSCLC patients without T790M mutation as those with T790M in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression &lt; 50% and may potentially gain benefit from optimizing treatment strategies including immunotherapy.
吸烟与慢性阻塞性肺疾病
Authors: 翁心植, 张洪玉
Journal: BMJ (1999)

布伦特兰博士于1998年5月13日在第51届世界卫生大会上当选为新的总干事，她宣布，上任后首先要抓控制吸烟和防治疟疾。烟草引起全球每年死亡人数达300万。若目前对吸烟情况不加抑制，到2025年每年死于烟草危害者将增至1000万。在我国，目前死于烟草危害者已达60～70万，到2025年将达200万。烟草雾首先进入呼吸道，故呼吸系统最大程度受到危害。在工业发达国家，肺癌是吸烟造成死亡的首要疾病；而在我国，大规模、高水平的流行病学调查结果显示，慢性阻塞性肺疾病（简称慢阻肺）是人们吸烟造成死亡的首要疾病。
Topical 5-ALA photodynamic therapy for the treatment of condylomta acnminnta
Authors: Mu-kai Chen, Ji-huang Xie, Yu-hua Li, Qi-man Liao, Jian-de Han
Journal: BMJ (2009)

20%ALA cream were applied topically to condylomata acuminata.The cream was kept in place for 4 h.He-Ne laser light at 630nm was used,and the dose of light was 100 J/cm2 for all of the patients.After three treatment,the complete removal rate(CRR)of urethral and other genital mucossa were 93.4%and 88.9%,significantly higher than genital skin 39.1%(P＜0.05).The adverse reactions of ALA-PDT are mainly local minor erosion,short-term pain,but no scar.It showed that ALA-PDT is an effective,minimally invasive treatment for condylomata acuminata,especially for the lesions on urethral and genital mucosa.

Key words: 
Condylomata acuminata; Photochemo therapy
Personalized combination of neoadjuvant domatinostat, nivolumab and ipilimumab in macroscopic stage III melanoma patients stratified according to the interferon-gamma signature: The DONIMI study.
Authors: Irene L.M. Reijers, Petros Dimitriadis, Elisa A. Rozeman, Judith M. Versluis, Annegien Broeks, Linda J.W. Bosch, Jasper Bouwman, Sten Cornelissen, Oscar Krijgsman, Maria Gonzalez, Disha Rao, Lindsay G Grijpink-Ongering, Marloes van Dijk, Andrew Spillane, Richard A. Scolyer, Bart A. Van De Wiel, Alexander M. Menzies, Alexander Christopher Jonathan Van Akkooi, Georgina V. Long, Christian U. Blank
Journal: Journal of Clinical Oncology (2020)

TPS10087 Background: Previous OpACIN and OpACIN-neo studies, investigating neoadjuvant ipilimumab (IPI) plus nivolumab (NIVO), demonstrated high pathologic response rates (74-78%) and favorable long-term outcomes in patients (pts) achieving pathologic response; at 36 and 18 months follow-up, respectively, only 1/71 (1.4%) pts with response has relapsed. In contrast, pts without pathologic response (pNR) have a poor prognosis; 15/23 (65.2%) have relapsed so far. This emphasizes the need for baseline biomarkers predictive of non-response and new neoadjuvant treatment combinations for these pts. In our previous studies, baseline interferon-gamma (IFN-γ) signature low pts were less likely to respond to neoadjuvant IPI plus NIVO. The DONIMI study tests the combination of NIVO +/- IPI with domatinostat (DOM), a class 1 histone deacetylase inhibitor, according to the IFN-γ signature in the tumor. Based on the signature previously described by Ayers et al. we have developed a neoadjuvant IFN-γ signature algorithm that will be used for the first time to classify pts in this prospective trial. Methods: The aim of this two-center investigator-initiated phase 1b study is to assess the safety and feasibility of neoadjuvant NIVO +/- DOM +/- IPI in 45 stage III melanoma pts with RECIST 1.1 measurable de-novo or recurrent disease. IFN-γ signature high pts (n = 20) will be randomized (stratified by center) to Arm A (2 cycles NIVO 240mg q3wk) or Arm B (2 cycles NIVO 240mg q3wk + DOM 200mg twice daily (BID), d1-14, q3wk). IFN-γ signature low pts (n = 25) will be randomized to Arm C (2 cycles NIVO 240mg q3wk + DOM 200mg BID, d1-14, q3wk) or Arm D (2 cycles NIVO 240mg q3wk + IPI 80mg q3wk + DOM 200mg once daily (OD), d1-14, q3wk). Based on safety data of the first 5 pts in arm D, the remaining pts will be treated with either a higher dosing scheme (200mg BID, d1-14, q3wks), a lower dosing scheme (100mg OD, d1-14, q3wks) or the same dosing scheme (200mg OD, d1-14, q3wks). The primary endpoint is safety and feasibility. A treatment arm will be declared as not feasible if 2/5 or 3/10 pts cannot adhere to the preplanned time of surgery (week 6 +/- 1week) due to treatment-related adverse events. Biopsies (week 0, 3), blood samples (week 0, 3, 6, 12) and feces (week 0, 3, 6) will be collected for translational research. The first patient was enrolled on January 23 th , 2020. Clinical trial information: NCT04133948.