tbuckley/cabot-search huggingface dataset:
The role of stromal tumor infiltrating lymphocytes (sTILs) as a predictive biomarker for carboplatin-based neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC).
Authors: Elaine M. Walsh, Mark O'Loughlin, Aliaa Shalaby, Mark Webber, Michael J. Kerin, Sharon A. Glynn, Grace Callagy, Maccon M. Keane
Journal: Journal of Clinical Oncology (2019)

e12085 Background: High numbers of sTILs are predictive of pCR in TNBCs. This study examines the role of sTILs as a predictive biomarker for carboplatin (Cb) based NACT. Methods: sTILs were scored on 88 pre NACT TNBC biopsies as per the International TILs Working Group and were scored as continuous and categorical variables: 0-10%; 11-25%; 26-49%; ≥50%. OR was calculated using non-pCR as baseline parameter. Results: Patients with sTILs &gt; 10% had increased pCR rates compared to those with sTILs ≤10%: pCR breast (B) (61% vs 31% p = 0.004); pCR breast/axilla (BA) (52% vs 29% p = 0.021). In those treated with Cb, there were no differences in pCR B between sTILs &gt; 10% or ≤10% (67% vs 53%; p = 0.355) or pCR BA (60% vs 53%; p = 0.500). In those who did not receive Cb, sTILs &gt; 10% had increased pCR B (57% vs 15%; p = 0.002) and pCR BA (46% vs 12%; p = 0.005) compared to sTILs ≤10%. Similar trends were seen with sTILs &gt; 25% and ≥50%: differences were seen in patients who did not receive Cb, but not in those treated with Cb. In LPBCs, the addition of Cb did not significantly increase pCR rates: 67% vs 83% for Cb and non-Cb regimens (p = 0.583). In non-LPBC, pCR rates were increased with Cb: pCR B 59% vs 31% (p = 0.017), and pCR BA 56% vs 23% (p = 0.005) for Cb and non-Cb regimens. The association between sTILs and pCR was significant in multivariable models adjusting for grade and Cb. In patients who did not receive Cb (n = 54), increasing sTILs were associated with increased pCR B (OR 0.15 p = 0.004; OR 0.27 p = 0.039; OR 0.10 p = 0.05 for &gt; 10%, &gt; 25%, ≥50%) and pCR BA (OR 0.18 p = 0.019; OR 0.08 p = 0.029 for &gt; 10%, ≥50%). In patients treated with Cb (n = 30), increasing sTILs were not associated with pCR B (OR 1.97 p = 0.581; OR 0.27 p = 0.334; OR 0.50 p = 0.719) or pCR BA (OR 2.93 p = 0.372; OR 0.79 p = 0.831; OR 0.40 p = 0.622 for &gt; 10%, &gt; 25%, ≥50%). Conclusions: sTILs are predictive of pCR: as sTILs increase, pCR rates increase. Tumors with high sTILs had high pCR rates to anthracycline-taxane (AT) NACT. The effect of increasing sTILs on pCR was most notable in patients who did not receive Cb based NACT, suggesting that tumors with high sTILs are inherently sensitive to AT based chemotherapy. Intensifying NACT with Cb could be used to increase pCR rates in patients with low sTILs. sTILs should be explored as a biomarker to intensify chemotherapy in those with low sTILs, and to de-escalate chemotherapy in tumors with high sTILs.
Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease
Authors: Harry Sokol, Loic Brot, Carmen Stefanescu, Claire Auzolle, Nicolas Barnich, Anthony Buisson, Mathurin Fumery, Benjamin Pariente, Lionel Le Bourhis, Xavier Treton, Stéphane Nancey, Matthieu Allez, Philippe Seksik
Journal: Gut (2019)

Following ileal resection for Crohn's disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence. Ileal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France. Ileal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors. Surgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
Effectiveness of scalp cooling in reducing chemotherapy-induced alopecia: A single center prospective study in Lebanon.
Authors: Nour Haidar, Lewis Nasr, Fadi Nasr
Journal: Journal of Clinical Oncology (2019)

e12075 Background: Hair loss (alopecia) is recognized as one of the most common and distressing side effects of chemotherapy. The scalp cooler first used in 1970s against the Chemotherapy CIA (chemotherapy induced alopecia). This study aimed at assessing the effectiveness of scalp cooling (PAXMAN Cooler ORBIS II SCALP COOLER) in reducing chemotherapy-induced alopecia. Methods: This prospective study was conducted at the Mount-Lebanon Hospital in the one day chemotherapy between 01 January 2017 and 31 December 2018. 109 women diagnosed with breast cancer with stage I or II undergoing neoadjuvant, and adjuvant chemotherapy were enrolled. Patients with scalp cooling 54.1% (n=59), control 45.9 % (n=50). Scalp cooling done by using the scalp cooling device. The primary end point was to assess the hair loss using the dean’s scale after multiple cycles of chemotherapy. The clinical assessment and alopecia evaluation were done after each chemotherapy cycle. The secondary endpoint was the side effect of the scalp cooler such as headache. Results: The Mean age was 55.73 ± 11.9 years. 82.56 %received Anthracycline-based chemotherapy regimen with Docetaxel, and 14.69 % Anthracycline-based chemotherapy regimen with Paclitaxel and 2.75 % took only anthracycline with cyclophosphamide. The effectiveness of hair preservation was successfully reported as 62.7% grade 0, 22.01 % grade 1 and 15.29% grade 2. There were highly significant differences between patients underwent scalp cooling and patients without scalp cooling with different regimens of chemotherapy (P value &lt;0.0001). The major side effect, the headache where was reported in 25.7% from the total (P value &lt;0.0001). Conclusions: Hair preservation in stage I , II breast cancer undergoing multiple regimens of chemotherapy was significantly more effective in the scalp cooling group.
KEYNOTE-629: Phase 2 study of pembrolizumab for recurrent/metastatic or locally advanced unresectable cutaneous squamous cell carcinoma (cSCC).
Authors: Jean Jacques Grob, Rene Gonzalez, Nicole Basset-Seguin, Jacob Schachter, Olga Vornicova, Jessica Ruth Bauman, Florent Grange, Nicolas Meyer, Josep M. Piulats, Eric (Pingye) Zhang, Burak Gumuscu, Ramona F. Swaby, Brett Gordon Maxwell Hughes
Journal: Journal of Clinical Oncology (2019)

TPS9598 Background: Findings from phase 1 and 2 studies suggest that targeting programmed death 1 (PD-1)/PD-L1 pathway can provide durable antitumor activity in patients with local/regionally advanced or metastatic cSCC and may be a promising treatment option. The open-label, single-arm, phase 2 KEYNOTE-629 trial (NCT03284424) will be conducted to test the clinical activity of the PD-1 inhibitor pembrolizumab in locally advanced, unresectable, and recurrent or metastatic cSCC. Methods: Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for up to 35 infusions (≤24 months) or until protocol-specified treatment discontinuation. Treatment will not be stratified in this study. Eligibility criteria include age ≥18 years; locally advanced cSCC for which the patient is ineligible for resection or radiotherapy (RT) or for which the patient previously underwent RT to the index site or systemic therapy for curative intent; presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; and Eastern Cooperative Oncology Group performance status 0 or 1. Treatment will be discontinued for progressive disease, unacceptable toxicity, intercurrent illness preventing administration, investigator’s decision, patient withdrawal of consent, pregnancy, or cessation for administrative reasons. Response will be assessed by imaging 6 weeks after treatment initiation, every 6 weeks through year 1, and every 9 weeks thereafter or more frequently if clinically indicated. After disease progression or the start of new anticancer therapy, the patient will be followed up every 12 weeks until death, consent withdrawal, or study end, whichever occurs first. Safety will be monitored throughout the study and for 30 days after treatment end or 90 days if the patient experiences serious adverse events. The primary end point is objective response rate (RECIST v1.1). Secondary end points include response duration, disease control rate, progression-free survival, overall survival, and safety. Recruitment is ongoing in 10 countries and will continue until approximately 50 additional patients with locally advanced, unresectable cSCC are enrolled. Clinical trial information: NCT03284424.
Drug funding price negotiations: Towards achieving a balance between individual and population gains in health benefits.
Authors: Ambika Parmar, Tina Jiao, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2019)

6641 Background: Drug price negotiation to lower cost to a cost-effectiveness threshold (λ) is a recognized approach to improve health care opportunities for the greater benefit of the population. Critics have raised concerns for this approach given the additional time required and speculated loss of quality-adjusted life-years (QALY) for patients. The current study aimed to quantify the incremental net health benefit (INHB) of publicly funded oncology drugs, if funding occurred at list prices without (w/o) negotiations. Methods: Pan-Canadian Oncology Drug Review submissions were reviewed to identify funded drugs with unique indications. For included drug indications economic guidance panel (EGP) reports were reviewed for incremental costs (ΔC) and ΔQALY from manufacturer’s base case cost-effectiveness analyses, EGP lower (LL) and upper limit (UL) re-analyzed estimates (based on list prices). Number of new cases in Ontario (most populous province in Canada) per indication (2017-18) was obtained from provincial databases. Annual QALY gain for each indication was determined by: (ΔQALY×cases). Provincial QALY gain/loss w/o price negotiations to reference λ was estimated by: (INHB= [ΔQALY− (ΔC/λ)] ×cases). Incremental net monetary benefit demonstrated annual monetary gain/loss w/o price negotiations to reference λ: (INMB= [(ΔQALY×λ) −ΔC] ×cases). Results: 34 drug indications including 4,629 new cases were identified. Annual QALY gain for funded indications using manufacturer, LL and UL estimates was 1,851, 1,617 and 1,301, respectively. At reference λ CAD$100,000/QALY, funding w/o negotiations resulted in loss of 2,176, 2,368, 2,451 QALY, representing budgetary diversions away from other health care interventions. This would result in a provincial net annual loss of 325, 751 and 1,150 QALY, respectively. INMB demonstrated provincial net monetary loss of CAD$32,472,389, $75,113,684 and $115,022,331, respectively. Conclusions: Despite an annual gain in QALY for funded drug indications, a net provincial loss in QALY w/o price negotiations was demonstrated. Thus, supportive evidence exists for drug price negotiations towards the promotion of health benefits for the population.
Clinical and immunological analyses of immune checkpoint inhibitor-associated neuromuscular (NM) toxicities.
Authors: Bilal A. Siddiqui, Jean-Bernard Durand, Jianjun Gao, Jianbo Wang, Ana Aparicio, Matthew T Campbell, Arlene O. Siefker-Radtke, Nizar M. Tannir, Paul Gettys Corn, Pavlos Msaouel, Amishi Yogesh Shah, Amado J. Zurita, Shi-Ming Tu, Maria E. Suarez-Almazor, Tummala Sudhakar, Christopher Logothetis, Padmanee Sharma, Sumit Kumar Subudhi
Journal: Journal of Clinical Oncology (2019)

e14118 Background: A rare and often fatal spectrum of NM immune-related adverse events (irAEs) includes myositis, myocarditis, and myasthenia gravis (MG). A deeper understanding of their clinical and immunologic features may improve outcomes. Methods: Sixteen patients (pts) with genitourinary cancers who were treated with ICI and developed myositis, myocarditis, MG, or overlap syndrome (≥2) were identified. Diagnostic criteria included serum CK (n=16), aldolase (n=14), troponin (n=12), BNP (n=15), autoantibodies (n=16), and cytokines (n=9). Biopsies of skeletal muscle (n=13) and endomyocardium (n=4) were also obtained. Immune profiling is being performed on blood and tissue for pts consented to an institutional-approved laboratory protocol. Results: ICI-associated NM irAEs consisted of isolated myositis (n=8, 50%), myocarditis (n=1, 6%), MG (n=1, 6%), or overlap syndrome (n=6, 38%), with the most common presenting symptom being weakness (n=9, 56%). CK levels were elevated in 15 (94%) pts, and autoantibodies were detected in 9 (56%). Muscle biopsies showed predominantly T cell infiltration. All 16 pts received corticosteroids, 12 (75%) were treated with other immunosuppressive agents, and 14 (88%) underwent plasmapheresis. Five pts (50%) with isolated irAEs achieved symptom resolution, and none in the overlap group. (Table) Conclusions: NM irAEs occurred more frequently with combination ICI, and were associated with weakness, and elevated CK level and serum autoantibodies. Both T and B cells appear to drive disease pathogenesis. The presence of one toxicity on the spectrum warrants evaluation for associated irAEs. Compared to isolated NM irAEs, the overlap syndrome appears to be more treatment refractory. Current guidelines require refinement to identify effective treatments to improve outcomes. [Table: see text]
Genes copy number variation in tumor cells of patients with metastatic and non-metastatic lung adenocarcinoma.
Authors: Denis S. Kutilin, Igor A. Leyman, Yuriy N. Lazutin, Anna V. Chubaryan, Pavel A. Anistratov, Oleg N. Stateshny, Igor N. Turkin, M. A. Gappoeva, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2019)

e14502 Background: Currently known markers of lung adenocarcinoma are insufficient to predict the development of this disease, which makes the search for new molecular markers a relevant problem. Our purpose was to analyze changes in genes copy number variation (CNV) in tumor and non-tumor cells of the lung in patients with (T1-3N1-2M0-1) and without (T1-3N0M0) metastasis to identify potential molecular markers for the prediction of the disease development. Methods: The study was performed on tissue sections from FFPE blocks of 90 patients diagnosed with lung adenocarcinoma. Tumor and non- tumor cells were isolated using laser microdissection (Palm MicroBeam, Carl Zeiss). Copy numbers of 32 genes (BAX, BCL2, C-FLAR, P53, MDM2, BFAR, SEMA3B, RASSF1A, CASP9, CASP3, CASP8, SOX2, OCT4, NANOG, PIK3, MKI67, HV2, HIF1A1, XRCC1, MMP1, TERT, CTNNB1, VEGFA, KRAS, EGFR, GRB2, SOS1, MAPK1, STAT1, BRAF, FTO, mir3678) were determined by Real-Time qPCR (ACTB, B2M, GAPDH - reference genes). Statistical analysis was performed using the Mann-Whitney test. Results: A pooled sample (n = 90) showed significant (p &lt; 0.005) increase in the copy numbers of MAPK1 and SOX2 and decreased copy numbers of the mir3678, HV2, BAX and CASP3 genes in tumor cells compared to non-tumor. Patients with metastatic and non-metastatic lung adenocarcinoma had significant (p &lt; 0.05) differences in genes copy number in tumor cells compared to non-tumor ones: patients with T1-3N1-2M0-1 (n = 50) – decreased copy numbers of the mir3678, HV2, MDM2, P53, XRCC1, CASP3 and OCT4 genes and increased SOX2 copy number; patients with T1-3N0M0 (n = 40) – increased copy numbers of the MAPK1 and mir3678 genes and decreased HV2 copy number. Conclusions: The detected changes in copy numbers of genes responsible for the regulation of apoptosis, proliferation, oxidative phosphorylation and the function of the EGFR signaling pathway in lung tumor cells revealed new molecular markers to predict the risk of metastasis ( mir3678, MDM2, Р53, SOX2, XRCC1, CASP3, OCT4, MAPK1).
Potential elimination of multi-drug resistant cancer cells by targeted non-engrafting intentionally mismatched activated donor lymphocytes.
Authors: Shimon Slavin
Journal: Journal of Clinical Oncology (2019)

e14007 Background: Immunotherapy by targeted autologous T cells, TIL or CAR-T, are considered most effective modalities for treatment of otherwise resistant cancer, yet cure is rarely achieved. In contrast, cure of resistant disease by donor lymphocyte infusion (DLI) following allogeneic stem cell transplantation suggests that alloreactive lymphocytes represent a most effective approach for elimination of resistant malignant cells. The first patient relapsing following supra-lethal chemoradiotherapy is alive &amp; well &gt; 34 years. Using murine B cell leukemia (BCL1) and metastatic breast cancer (4T1) we proved that non-engrafting intentionally mismatched lymphocytes activated with IL-2 that were consistently rejected cured otherwise lethal cancer with no graft-vs-host disease (GVHD). Methods: We first applied graft-vs-tumor effects by non-engrafting Intentionally Mismatched Activated Killers (IMAK) following mild immunosuppressive conditioning to maximize homeostatic proliferation of activated T &amp; NK cells. IMAK was first applied inpatients with multiple myeloma and lymphoma treated with donor lymphocytes pre-activated in vitro prior to infusion and for 5 days following infusion withlow dose IL-2.We next studied feasibility of Allogeneic Targeted Activated Cancer Killer cells (ATACK) using IL-2 activated haploidentical donor lymphocytes including T &amp; NK cells targeted against antigens over-expressed on the surface of malignant cells: Her-2/neu, EGFR, VEGF and CD20 using commercially available Herceptin, Erbitux, Avastin or Rituximab, respectivelyin a pilot study involving 16 patients with advanced metastatic solid tumors. Results: Using IMAK donor lymphocytes were uniformly rejected and no patient developed GVHD. Disease-free survival &gt; 20 years was documented in our first myeloma patient with plasmacytomas and in another relapsing after autologous SCTand in 2 patients with non-Hodgkin lymphoma. Longterm progression-free survival was reported in 5 of 31 patients with resistant solid tumors. Following ATACK transient mild toxicity was manageable in outpatient clinic and no GVHD developed. Conclusions: Using ATACK against minimal residual disease accomplishable by most cancer patients following conventional 1st line treatment may result in cure of otherwise resistant cancer while avoiding GVHD.
Disparities in survival by insurance status in chronic lymphocytic leukemia.
Authors: Kahee A. Mohammed, Noor Al-Hammadi, Lana Hamieh, Nosayaba Osazuwa-Peters, Leslie J. Hinyard
Journal: Journal of Clinical Oncology (2019)

e18134 Background: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in western world. It is the disease of older adults with a median age at diagnosis of approximately 70 years. However, significant proportion of younger adults are diagnosed with CLL and they usually have an adverse clinical and molecular risk profile necessitating early interventional strategies compared to older patients. Socioeconomic disparities may affect survival for some patient populations. This study examined survival by insurance status for younger patients with CLL. Methods: The Surveillance, Epidemiology, and End Results database was used to identify patients, aged 15 - 64 years, who were diagnosed with CLL between 2007 and 2014 and whose insurance status (no insurance, Medicaid, and other insurance) was documented at diagnosis. Unadjusted associations between insurance status and overall survival (OS) were plotted using Kaplan-Meier curves. The association between insurance status and CLL-specific mortality was assessed using multivariate Cox proportional hazards regression models, adjusting for sociodemographic covariates. Results: A total of 10,913 patients with CLL were included with a median follow up of 44 months. Five-year survival estimates were 87.3%, 87.2%, and 94.0% for patients with no insurance, Medicaid, and other insurance, respectively. In multivariate analysis, compared to patients with other insurance, patients with no insurance (hazard ratio [HR] = 2.33, 95% confidence interval [CI] = 1.73 – 3.140) and Medicaid (HR = 1.95, 95% CI = 1.49 – 2.54) had significantly worse OS survival after adjusting for sociodemographic factors. Conclusions: Younger patients with no insurance or Medicaid have lower survival outcomes after diagnosis with CLL compared to patients with other insurance. Addressing barriers to care, providing resources, and expanding access to care is paramount to reducing the gap in survival for the uninsured patients and those with lower socioeconomic status. Further studies are needed to address poor survival outcomes among Medicaid patients.
Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma
Authors: Federico Rotolo, Jun Ma, Jean-Pierre Pignon, Yuk Tung, Georgios Fountzilas, Yoke Lim Soong, Anthony T. C. Chan, Guopei Zhu, Sophie Marguet, Pierre Blanchard, Dora L. W. Kwong, James Moon, Pei-Yu Huang, Stefan Michiels, Daniel T. T. Chua, Kwan-Hwa Chi, Li Zhang, Hai-Qiang Mai, Wai Tong Ng, Edwin Pun Hui, Anne W. M. Lee, Yong Chen, Jean Bourhis, Julie Leclercq
Journal: JNCI Journal of the National Cancer Institute (2017)
Optimal body mass index cutoff point for predicting survival of colorectal cancer in Asian population: A National Health Information Database Analysis.
Authors: Nan Song, Aesun Shin, Dan Huang, Minjung Kim, Ji Won Park
Journal: Journal of Clinical Oncology (2019)

e13098 Background: A U-shaped relationship between body mass index (BMI) and colorectal cancer mortality has been revealed. However, an optimal BMI range for predicting survival in Asian colorectal cancer patients is unknown. We established the most appropriate cut-off point of BMI for better survival in Asian colorectal cancer patients. Methods: Two cohorts of colorectal cancer patients were included in this study; 5,815 from the Seoul National University Hospital, Korea for development cohort and 54,043 colorectal cancer patients from the Korean National Health Information Database for validation cohort. To determine the optimal cut-off point of BMI at diagnosis, the systematic dichotomization based on log-rank test was performed by the method of Contal and O’Quigley. We evaluated the association between BMI at diagnosis and overall survival (OS) using the Cox proportional hazard model. Results: During a median follow-up of 5.7 years for hospital-based development cohort and 4.3 years for nation-wide validation cohort, 1,180 (20.3%) deaths and 10,244 (19.0%) deaths occurred, respectively. The optimal cut-off point of BMI at diagnosis was identified at 20.2 kg/m 2 (log-rank statistic = 96.69, Q-statistic = 3.07, P&lt; 0.01) for differentiating between the poorer and better OS in development cohort. When compared to the patients with BMI &lt; 20.2 kg/m 2 , the patients with BMI ≥20.2 kg/m 2 were significantly associated with the better OS in the Cox proportional hazard regression analysis (HR = 0.62, 95% CI = 0.54-0.72, P= 1.1×10 -10 ). The association was validated in the nation-wide cohort showing the better OS in the patients with BMI ≥20.2 kg/m 2 . (HR = 0.64, 95% CI = 0.60-0.67, P&lt; 0.01). Conclusions: We suggest the use of a BMI value of 20.2 kg/m 2 to predict survival in Asian colorectal cancer patients.