tbuckley/cabot-search huggingface dataset:
Combination therapy with nivolumab and tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma.
Authors: Benjamin Garmezy, Tian Zhang, Andrew Leonard Laccetti, Minas P. Economides, Amishi Yogesh Shah, Nizar M. Tannir, Eric Jonasch, Pavlos Msaouel, Amado J. Zurita, Paul Gettys Corn, Aradhana M. Venkatesan, Landon Carter Brown, Chester Kao, Emily Noelle Kinsey, Michael Roger Harrison, Andrew J. Armstrong, Daniel J. George, Matthew T Campbell
Journal: Journal of Clinical Oncology (2020)

e17090 Background: Two immunotherapy (IO) and tyrosine kinase inhibitor (TKI) combinations are FDA-approved for patients (pts) with metastatic renal cell carcinoma (mRCC). Here we present a multicenter off-protocol experience with IO/TKI combinations after progression on monotherapy. Methods: We performed a retrospective analysis of pts with mRCC who received combination non-FDA approved off-protocol IO/TKI combination therapy from 11/2015 – 1/2019 at MD Anderson Cancer Center and Duke Cancer Institute. Results: 48 pts met criteria for study inclusion. At therapy start: median (med) age 65 years; 75% clear cell histology; 68.8% IMDC intermediate risk (20.8% favorable, 10.4% poor); 81.3% prior nephrectomy; med metastatic sites: 2; med prior systemic treatments: 2; most common metastatic sites: lung (58.3%), lymph node (52.1%), and bone (43.8%). Pts received nivolumab (nivo) in combination with the following: cabozantinib (n = 24, 50%), pazopanib (13, 27.1%), axitinib (6, 12.5%), lenvatinib (2, 4.2%), ipilimumab/cabozantinib (3, 6.3%). Med PFS was 13.7 months and med OS was not reached. The two largest cohorts received nivo + cabozantinib (N+C; med dose 40 mg daily) or nivo + pazopanib (N+P; med dose 400 mg daily). The N+C cohort had higher med metastatic sites (3 vs 2) and was more pretreated with agents unique to their IO/TKI combination (med 2 vs 0). In the N+P group, more pts had started on TKI prior to addition of nivo at progression (69.2% vs 45.8%), and fewer had IO monotherapy with TKI addition (30.8% vs 50%). With a med follow up of 14.0 months after combination start, the N+C cohort had a med PFS of 7.3 months (initiated TKI first: 4.8, IO first: 8.2) and med OS of 18.2 months (TKI first: 11.8, IO first: 24.3). The N+P cohort had med follow up of 20.5 months after combination, med PFS of 21.3 months (TKI first: 16.5, IO first: 21.8), and med OS was not reached. In the N+C group, 87.5% experienced any grade adverse event (AE), most common included fatigue (79.2%), diarrhea (42.7%), nausea (29.2%), hypertension (29.2%), and weight loss (25.0%). In the N+P group, 92.3% experienced any grade AE, including fatigue (76.9%), hypertension (38.5%), diarrhea (30.8%), nausea (30.8%), and weight loss (30.8%). There were no grade ≥3 AEs. Conclusions: Slow disease progression on nivo or TKI may be safely controlled with addition of IO/TKI therapy. Med PFS after addition of nivo to TKI appears similar (N+C) and improved (N+P) compared to nivo monotherapy (Checkmate-025). Med PFS after addition of TKI to IO was also similar (N+C) and improved (N+P) compared to historical controls.
Prognostic characteristics of patients with benign mesenteric lymph node enlargement after surgical resection for colorectal cancer.
Authors: Fei Tian, Gong Chen
Journal: Journal of Clinical Oncology (2020)

4027 Background: Patients with lymph node metastasis of colorectal cancer (CRC) have a greater risk of recurrence. However, the characteristics of benign mesenteric lymph node enlargement (BLNE) are not well documented. The aim of this study is to assess clinical and prognostic significance of BLNE in patients with CRC. Methods: 601 patients who underwent surgery for stage 0, I, II CRC from January 2010 to April 2014 were included and separated into two groups by presence of BLNE. Univariate and multivariate analyses were constructed to demonstrate prognostic factors between BLNE group (n = 275) and control group (n = 326). Results: The risk of recurrence in BLNE group after curative resection was significantly lower than control group, with the 1-, 3-, and 5-year disease-free survival rates being 98.2, 91.6, and 86.9 %, in BLNE group and 95.7, 86.2, and 78.2 %, in control group respectively (p = 0.004). The mortality in BLNE group was lower compared with non BLNE group (mean overall survival: 95.7±1.2 vs. 89.5±1.4 months, p = 0.001). Patients of BLNE group also had a higher percentage of younger age, family tumor history, left sided tumors and tumor size ≥4cm. Adjusted Cox regression showed BLNE was an independent prognostic factor for both disease free survival and overall survival ( P= 0.003 and 0.001). Conclusions: The study indicates that BLNE can be a useful positive factor in predicting recurrence and long-term survival concerning CRC patients. This conclusion offers a new viewpoint about CRC genesis and progression.
Comparison of psychological health status between infertile women with and without polycystic ovary syndrome
Authors: Sai-jiao Li, Jing Yang, Tai-lang Yin, Wang-ming Xu, Wei Li, Lu Wang
Journal: BMJ (2011)

One hundred and twenty-two infertile women with polycystic ovary syndrome (PCOS) and 112 infertile women without PCOS were interviewed with symptom checklist 90 ( SCL-90) and questionnaire of demographic and clinical characteristics to understand their psychological health status. Results demonstrated that scores of depression, interpersonal sensitivity, obsessive-compulsive and aggressive symptoms in infertile patients with PCOS were significantly higher than those in non-PCOS infertile ones (P < 0. 05 ). Acne had negative effect on their psychological health status (OR =3. 379, 95% CI = 1.096 ±10.419) . Scores of somzatization, interpersonal sensitivity, anxiety, obsessive-compulsive, aggressive and paranoid ideation symptoms were significantly higher in secondary infertile patients with PCOS than those in primary infertile ones (P<0. 05). Patients with PCOS had obviously psychological problems, especially in secondary infertile patients with PCOS ( P < 0. 05 ). Thus, it is suggested that psychological health status be evaluated in clinical diagnosis for infertile women so that they can be predicted and treated to improve its effectiveness.

Key words: 
Polycystic ovary syndrome; Mental health
Adult Langerhans cell histiocytosis: a report of 2 cases
Authors: Ke Ding, Miao-bing Liu
Journal: BMJ (2010)

Two cases of adult Langerhans cell histiocytosis were retrospectively reviewed. Both caseswere male cigarette smokers, aged 39 and 45. Chest pain was the major symptom in one case and radiologyshowed lesions in the right ribs. Another case was admitted because of the shadow in the chest X-raydiscovered during routine physical examination. Lung cysts and reticular changes were shown in the high-resolution CT scan, predominantly in the upper and middle lung fields. Pathological diagnosis wereestablished though surgical bone biopsy or thoracoscopic lung biopsy respectively. Specific Langerhans cellswere detected udder light microscope and staining for the S-100, CD1a antigens were all positive in twocases.

Key words: 
Histiocytosis, langerhans-cells
Abstract 15329: Clinical and Angiographic Factors Contributing to Discrepancy Between Angiographic and Fractional Flow Reserve Estimation in Intermediate Coronary Stenosis
Authors: Kakehi Kazuyoshi, Yoshitaka Iwanaga, Heitaro Watanabe, Masafumi Ueno, Tomoyuki Ikeda, Toru Takase, Kenji Yamaji, Kazuhiro Kobuke, Shunichi Miyazaki
Journal: Circulation (2017)

Background: Visual-functional mismatch between angiographic and fractional flow reserve (FFR) analyses has been reported and the contributing factors remain poorly understood. Therefore, we evaluat...
Pressurized intra peritoneal aerosol chemotherapy (PIPAC) vs. intravenous chemotherapy to assess quality of life &amp; response rates in unresectable peritoneal metastases secondary to platinum resistant ovarian cancer: A comparative study.
Authors: S.P. Somashekhar, Rohit Kumar C., Ashwin K. Rajgopal, Amit Rauthan, Poonam Patil, Priya Kapoor
Journal: Journal of Clinical Oncology (2020)

e18091 Background: The primary objective of this study is to assess Qol &amp; response rates in platinum resistant ovarian cancer patients with peritoneal metastasis treated with PIPAC procedure in comparison with conventional systemic intravenous chemotherapy. Methods: Between October 2017 and December 2019, 31 PIPAC applications were done in 15 patients with cisplatin 10.5mg/m 2 and doxorubicin 2.1mg/m 2 . During same period 20 patients received systemic chemotherapy with clinician’s choice of drug ((mono-therapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly with or without bevacizumab).The response rate (With MRI &amp; Ca-125) &amp; quality of life assessment (QLQ C-30) of both the group was done periodically and recorded. Results: Overall 35 patients were analysed in this study. The results have been presented in Table. Conclusions: PIPAC in comparison to intravenous chemotherapy for platinum resistant ovarian cancer with peritoneal metastasis showed better response rates (66.6 vs. 22.4%) and improved quality of life score. PIPAC has shown promising results and should be in the arsenal of the clinicians managing patients with platinum resistant ovarian cancer. [Table: see text]
SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA).
Authors: Davendra Sohal, Mai T. Duong, Syed A. Ahmad, Namita Gandhi, Muhammad Shaalan Beg, Andrea Wang-Gillam, James Lloyd Wade, Elena Gabriela Chiorean, Katherine A Guthrie, Andrew M. Lowy, Philip Agop Philip, Howard S. Hochster
Journal: Journal of Clinical Oncology (2020)

4504 Background: Clinical outcomes after curative treatment of resectable PDA remain suboptimal. To assess the potential of early control of systemic disease with multiagent peri-op CTx, we conducted a prospective trial in the National Clinical Trials Network. Methods: S1505 was a randomized phase II trial of peri-op CTx (12 weeks pre-, 12 weeks post-op) with either mFOLFIRINOX (Arm 1) or Gem/nabP (Arm 2). Eligibility required confirmed tissue diagnosis of PDA, ECOG PS 0 or 1, and resectable disease per Intergroup criteria. Primary outcome was 2-year overall survival (OS), using a “pick the winner” design; for 100 eligible patients (pts), accrual up to 150 pts was planned to account for cases deemed ineligible at central radiology review. We previously presented data on eligibility (ASCO 2019 abstr 4137). Here we present the final efficacy and toxicity results for the eligible pts. Results: From 2015 to 2018, 147 pts were enrolled; there were 102 eligible pts; 55 in Arm 1; 47 in Arm 2. For Arms 1 and 2 respectively: median age, 66 (44-76) and 64 (46-76) years; males, 36 (65%) and 24 (51%); and ECOG PS 0, 34 (62%) and 31 (66%) pts. Treatment details are shown in Table. For Arm 1 and Arm 2, respectively: Two-year OS was 41.6% and 48.8%; median OS was 22.4 months and 23.6 months. Neither arm’s 2-year OS estimate was statistically significantly higher than the a priori threshold of 40% (p=0.42 in Arm 1 and p=0.12 in Arm 2). Median disease-free survival (DFS) after resection was 10.9 months in Arm 1 and 14.2 months in Arm 2 (p=0.87). Conclusions: We have demonstrated: 1) two-year OS of 41.6% (median 22.4 months) with mFOLFIRINOX and 48.8% (median 23.6 months) with Gem/nabP for all eligible pts starting treatment for resectable PDA; 2) post-resection DFS of 10.9 months and 14.2 months, respectively; 3) adequate safety and high resectability rates with peri-op CTx; 4) little evidence that either regimen improves OS compared with the historical standard. Clinical trial information: NCT02562716 . [Table: see text]
Clinical features of allergic granulomatosis polyangiitis with neurologic involvement: an analysis of 5 cases
Authors: Zhengjuan Lu, Yun Luo
Journal: BMJ (2020)

Ten patients with allergic granulomatosis with polyangiitis (AGPA) were admitted in Nanjing Drum Tower Hospital during January 2013 to August 2019, among whom 5 cases with neurologic involvement. The clinical features, laboratory findings and clinical outcome of the 5 patients were analyzed and literature review was performed. Among 5 cases of AGPA with neurologic involvement, 3 presented with peripheral neuropathy as the initial symptom, 2 had multiple mononeuropathy, 3 had distal asymmetric or symmetric polyneuropathy. All five patients had acute or subacute onset, and the symptoms of limb numbness or pain were prominent. Electrophysiological examination showed that sensory and motor conduction amplitude significantly decreased or disappeared. Eight of the 10 AGPA patients were treated with corticosteroid combined with immunosuppressants, 2 were treated with corticosteroid alone. Eight patients had good prognosis and 2 patients died. The results suggest that peripheral neuropathy is common in AGPA. When the patients present with acute or subacute onset of axonal impairment of peripheral neuropathy and elevated eosinophils, AGPA should be considered.


Key words: 
Churg-Strauss syndrome; Peripheral nervous system; Pathological conditions, signs and symptoms
Utility of circulating tumor DNA in genomic profiling of colorectal cancer with peritoneal metastasis.
Authors: Tenghui Ma, Weiguo Cao, Jin Huang, Yuguang Song, Lingjun Zhu, Lianke Liu, Yun-Bo Zhao, Jun Bai, Li Liang, Fei Ma, Mingming Yuan, Rongrong Chen, Hui Wang
Journal: Journal of Clinical Oncology (2020)

e16057 Background: Patients (pts) with peritoneal metastatic (PM) colorectal cancer (CRC) have significantly poorer prognosis than those with other metastases. In this study, we aim to investigate genomic profiles of PM-CRC and metastatic CRC without peritoneal involvement (non-PM-CRC) and PM-CRC with other organ involvement (PM-CRC+) using circulating tumor DNA (ctDNA)-based sequencing. Methods: A total of 169 pts with metastatic CRC were enrolled irrespective of treatment history, including 53 pts with non-PM-CRC, 47 pts with PM-CRC, and 69 pts with PM-CRC+. Matched tumor-normal next-generation sequencing of 1021 cancer-related genes was performed on ctDNA and white blood cells derived from plasma samples. The differences of mutation number were examined with student t test, and the differences of mutation detection rate were examined with two tailed Fisher’s exact test. p≤0.05 was considered statistically significant. Results: Somatic mutations were identified in 96% of pts with non-PM-CRC, 77% of pts with PM-CRC, and 97% of pts with PM-CRC+. The number of somatic mutations observed in the PM-CRC cohort was significantly lower than that in the other cohorts with the median value of 2 in the PM-CRC cohort, 9 in the non-PM-CRC cohort, and 7 in the PM-CRC+ cohort (p = 0.0002 and p &lt; 0.0001, respectively). The most frequently mutated genes in these cohorts was listed in Table. The detection rate of APC and TP53 mutations in the PM-CRC cohort was significantly lower than the other cohorts. Significant differences were also observed when comparing TCF7L2 mutations in the non-PM-CRC and the other cohorts, LRP1B mutations in the PM-CRC cohort and PM-CRC+ cohort, and NOTCH4 and PCK1 mutations in the non-PM-CRC and PM-CRC+ cohorts. In addition, BRAF mutations were more commonly observed in the PM-CRC cohort (13%) than the other cohorts (8% for non-PM-CRC cohort, 4% for PM-CRC+ cohort) (p = 0.51 and 0.16, respectively). Conclusions: Pts with PM-CRC exhibit a distinct molecular profile compared with non-PM-CRC and PM-CRC+, which may be helpful to explain their relatively poor prognosis and potentially be used in the early diagnosis of PM. [Table: see text]
Assess how non-oncology care settings influence the longitudinal journey of cancer patients.
Authors: Daniel Carnegie, Elenee Argentinis, Dibyajyoti Mazumder
Journal: Journal of Clinical Oncology (2020)

e19254 Background: Electronic health records (EHRs) are increasingly being accepted by regulators and as real world evidence (RWE). In a recent literature review (published elsewhere in this conference), we identified that many of the commercial databases source data solely from oncology clinics. This analysis aimed to understand the extent to which melanoma skin cancer patients receive cancer care specialties other than oncology. Methods: Newly diagnosed melanoma patients with one or more melanoma encounters (ICD10 CM) from January-Dec 2017 were included from the Optum Electronic Health Record Data Repository. Optum EHR data repository has more than 90 million de-identified patient lives mostly sourced from integrated healthcare delivery network EHRs within the US. Optum data includes the entire care continuum across primary case, across specialties, inpatient and outpatient encounters. Index date was defined as the first date of melanoma diagnosis within the study period. EHR history was assessed for 6 months prior to index and 1 year post index. All pathology, radiology and treatment encounters were identified, and all specialties who participated in the patient’s oncology diagnosis and care were counted. All ICD codes were verified by certified medical professional. Results: A total 7351 patients had one or more melanoma related encounters in 2017. During the 6 months prior to diagnosis, histological tests were ordered mostly by dermatologists (38%), followed by pathologists (19%), while oncologists and surgeons ordered 6% and 5%, respectively. Analysis of surgical excision on or after index indicated that dermatologists performed 47% of procedures followed by plastic surgeons (10%) and oncologists (9%). Oncologists comprised 44% of chemotherapy prescribing, while general medicine accounted for 14%. Conclusions: A large proportion of dermatological cancer care encounters occur outside the oncology setting. Therefore, to understand the factors that affect treatment outcomes, the EHR data used for outcomes research should include the entire care continuum.
Phase Ib study assessing different sequencing regimens of atezolizumab (anti-PD-L1) and sipuleucel-T (SipT)in patients who have asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.
Authors: Charles Joel Rosser, Yosuke Hirasawa, Jared David Acoba, David Jon Tamura, Sumanta K. Pal, Jeffrey Huang, Mark C. Scholz, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2020)

e17564 Background: Combining an immune checkpoint inhibitor with a tumor vaccine may leverage complementary mechanisms of action for treatment of mCRPC. Atezolizumab, a fully human anti–PD-L1 IgG1 antibody, is an approved treatment option in multiple indications; while SipT, an autologous cellular immunotherapeutic, is approved for treatment of metastatic castrate resistant prostate cancer (mCRPC). We present a phase Ib study evaluating safety, tolerability and objective response rate of atezolizumab + SipT in patients with mCRPC (NCT03024216). Methods: Eligible patients who had asymptomatic or minimally symptomatic progressive mCRPC and met standard criteria for sipuleucel-T were randomized to receive either atezolizumab 1200 mg IV every 3 weeks for 2 doses then SipT IV every 2 weeks for a total of three infusions (Arm 1) or SipT IV every 2 weeks for a total of three infusions followed by atezolizumab 1200 mg IV every 3 weeks for 2 doses (Arm 2). The primary endpoint was safety, while secondary endpoints included objective tumor response (PCWG2 and modified RECISTv1.1 criteria) and comparing systemic immune responses after induction between the arms. Results: As of February 6, 2020, 37 pts (median follow-up 7.4 months, median age 75 yrs [range 53.0–86.0]; median number of previous treatments 4 [range 1-8], 75.7% ECOG PS = 0) were enrolled. Three patients did not complete induction therapy (1 – withdrew consent, 1 developed toxicity, and 1 progressed). There were no grade 5 toxicities attributed to study drugs and grade 4 toxicities were noted in 2 patients, 1 in each arm (Arm 1 bronchitis and Arm 2 hypotension). Eight grade 3 toxicities were noted in arm 1 (hyponatremia, pulmonary embolus x3, bone pain, hypophosphatemia, shock, tooth fracture from a fall), while 4 grade 3 toxicities were noted in arm 2 (anemia, hypertension x 2, pneumonia). None of the grade 3 or 4 SAEs were noted to be irAEs. At 6 months, there were 11 SD (7 in Arm 1 and 4 in Arm 2), 18 PD and 7 unevaluable (3 withdrew from study and 4 have yet to reach 6 month evaluation). At this time, PFS was noted to be 8.2 months in Arm 1 and 5.8 months in Arm 2 (p = 0.054). Conclusions: The safety profile of the combination of atezolizumab with sipuleucel-T appears manageable in a heavily pre-treated population and consistent with those agents administered as monotherapy. Responses were seen but no CR. Immune activation studies may shed light on which sequence is optimal. Clinical trial information: NCT03024216 .
The anti–PD-1 antibody spartalizumab in combination with dabrafenib and trametinib in advanced <i>BRAF</i> V600–mutant melanoma: Efficacy and safety findings from parts 1 and 2 of the Phase III COMBI-i trial.
Authors: Georgina V. Long, Celeste Lebbe, Victoria Atkinson, Mario Mandalà, Paul D. Nathan, Ana Arance, Erika Richtig, Naoya Yamazaki, Caroline Robert, Dirk Schadendorf, Hussein Abdul-Hassan Tawbi, Paolo Antonio Ascierto, Antoni Ribas, Keith Flaherty, Neha Pakhle, Aisha Masood, Eduard Gasal, Reinhard Dummer
Journal: Journal of Clinical Oncology (2020)

10028 Background: Treatment (tx) with checkpoint inhibitors or targeted therapy improves outcomes in patients (pts) with BRAF V600–mutant advanced melanoma; however, many pts subsequently progress and die. Preliminary evidence suggests that targeted therapy may enhance the impact of checkpoint inhibitors and improve efficacy compared with either treatment alone. Methods: COMBI-i is investigating first-line spartalizumab 400 mg every 4 wk + dabrafenib 150 mg twice daily + trametinib 2 mg once daily in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). We report efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort), with a median follow-up of 24.3 mo. Response was assessed per RECIST v1.1. The randomized part 3 is ongoing. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 20 (56%) had stage IV M1c disease and 15 (42%) had elevated lactate dehydrogenase (LDH) levels (≥ upper limit of normal). At the data cutoff (August 19, 2019), tx was ongoing in 10 pts (28%). The confirmed investigator-assessed objective response rate (ORR) was 78% (n = 28), with 16 complete responses (CRs; 44%) and 12 partial responses (33%). Median duration of response (DOR; 10/28 responders with events) was not reached (NR); 24-mo DOR rate was 53.4% (95% CI, 29%-73%). Median progression-free survival (PFS) was 22.7 mo; 24-mo PFS rate was 41.4% (95% CI, 23%-59%). At the cutoff, median overall survival (OS) was NR, with a 24-mo OS rate of 74.1% (95% CI, 56%-86%). In pts with elevated LDH, ORR was 67%, with 4 CRs (27%); median PFS was 10.7 mo (95% CI, 4.6-19.1 mo), and median OS was NR. The estimated 24-mo PFS and OS rates in these pts were 26.7% and 52.5%, respectively. All pts had ≥ 1 tx-related adverse event (TRAEs); 26 (72%) had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs were pyrexia (17%), increased lipase (11%), neutropenia (11%), increased blood creatine phosphokinase (8%), and increased γ-glutamyltransferase (8%). AEs leading to discontinuation of all 3 study drugs occurred in 6 pts (17%). All-causality grade ≥ 3 AEs requiring immunosuppressive medication occurred in 19 pts (53%). One pt died of cardiac arrest that was not considered tx related. Conclusions: The combination of spartalizumab + dabrafenib + trametinib resulted in high ORR and CR rates, with a high frequency of durable responses, including in patients with poor prognostic factors. Clinical trial information: NCT02967692.