tbuckley/cabot-search huggingface dataset:
A randomized phase II study of ipilimumab at 3 (ipi3) or 10 mg/kg (ipi10) alone or in combination with high dose interferon-alfa (HDI) in advanced melanoma (E3611).
Authors: Ahmad A. Tarhini, Sandra J. Lee, Uma N. M. Rao, Arun Nagarajan, Mark R. Albertini, Jerry W Mitchell, Stuart J. Wong, Mark A. Taylor, Noel Laudi, Phu Van Truong, Robert Martin Conry, John M. Kirkwood
Journal: Journal of Clinical Oncology (2017)

9542 Background: Interferon-α (IFN) favors a Th1 shift in immunity. Combining CTLA4 blockade with IFN may downregulate CTLA4 suppressive elements. Prior data from a phase II of tremelimumab and HDI showed promising efficacy supporting the current study. Methods: E3611 had a 2x2 factorial design (A: ipi10 + HDI; B: ipi10; C: ipi3 + HDI; D: ipi3) to evaluate (i) no HDI vs. HDI (across ipi doses) and (ii) ipi3 vs. ipi10 (across HDI status). We hypothesized that median progression free survival (PFS) would improve from 3 to 6 months (mos) with HDI vs. no HDI and with ipi10 vs. ipi3. Based on the log-rank test for 80 patients (pts) these comparisons would have 82% power at 2-sided type I error of 0.10. Results: Median follow up 26.4 mos. PFS and overall survival (OS) (eligible and treated pts; N = 80: 18 III/M1a, 24 M1b, 38 M1c) are shown in Table 1. There were no significant differences in PFS or OS when evaluating HDI vs. no HDI or ipi10 vs. ipi3 (Table 1). Response (RECIST) among response evaluable pts (and 4 pts with early death) (N = 76) is shown in Table 1. Stable disease (SD) in 7 (A), 6 (B), 8 (C) and 6 (D). Adverse events (AEs) were consistent with the toxicity profiles of ipi and HDI and included 3 grade 5 AEs considered at least possibly related: 1 in A (suicide), 1 in B (lung infection and hemorrhage) and 1 in C (adult respiratory distress syndrome). One patient in B died of gastrointestinal bleed and cardiac arrest while on corticosteroids to treat temporal arteritis and vision loss. Conclusions: Within the limitations of the sample size, there were no significant differences in PFS with HDI vs. no HDI or ipi10 vs. ipi3. Response and PFS with ipi10 were superior to historical controls and similar to the combination. Correlative studies are ongoing. Clinical trial information: NCT01708941. [Table: see text]
Exposure-response (ER) analysis of alectinib (ALC) in crizotinib-resistant ALK-positive non-small cell lung cancer (NSCLC).
Authors: Peter N. Morcos, Felix Jaminion, Elena Guerini, Joy Hsu, Francois Mercier
Journal: Journal of Clinical Oncology (2018)

e21137 Background: A pooled overall survival (OS) analysis of two single-arm, open-label phase II studies (NP28673, global [NCT01801111] and NP28761, North American [NCT01871805]) with 53.3% of deaths, demonstrated a median OS for ALC 600 mg twice daily (BID) of 29.1 months (95% CI: 21.3–39.0) in crizotinib-resistant ALK+ NSCLC (Ou et al, ASCO 2018). We investigated ER relationships from final pooled phase II OS and safety data. Methods: A semi-parametric Cox proportional hazards (CPH) model investigated the relationship between individual median observed steady-state trough concentrations (Ctrough,ss) for combined exposure of ALC and M4 metabolite along with baseline covariates (demographics and disease characteristics) and OS. Univariate logistic regression analysis explored the relationship between Ctrough,ss and incidence of serious adverse events and Grade ≥3 adverse events. Results: A total of 207/225 (92%) patients had Ctrough,ss data and were included in the analysis. CPH confirmed no statistically significant relationship between Ctrough,ss and OS (95% CI for effect contains 1) over a 9-fold exposure range following ALC 600 mg BID. Log (baseline tumor size) and prior crizotinib treatment duration were the only covariates which statistically influenced OS (Table 1). Larger baseline tumor size and shorter prior crizotinib treatment were associated with worse OS. Logistic regression confirmed no significant relationship (p > 0.4) between Ctrough,ss and safety events. ALC 600 mg BID provides systemic exposures at plateau of response for OS while maintaining a well-tolerated safety profile. Conclusions: The ER analyses confirm that ALC 600 mg BID is the recommended dose for the Global crizotinib-resistant ALK+ NSCLC population. Table 1: Summary of Covariate Effects for OS from the Final Cox Proportional Hazards Model Clinical trial information: NP28673;NCT01801111; NP28761; NCT01871805.Covariate Median (5th and 95th Percentile) Hazard Ratio (95% CI) Relative to Median Log(Baseline Tumor Size [mm2]) 3.78 2.56 0.520 (0.376–0.719) 4.98 1.90 (1.38–2.61) Prior Crizotinib Duration (Days) 366 63.8 1.44 (1.15–1.80) 999 0.465 (0.293–0.740)
Pre-therapy neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio do not predict survival in patients treated with immune checkpoint inhibitors.
Authors: Hashim Mann, Muhammad Umair Mushtaq, Xavier Alberto Andrade Gonzalez, Ahmed T Ahmed, Shweta Gupta
Journal: Journal of Clinical Oncology (2018)

e15092 Background: Inflammatory and immune responses in the tumor microenvironment play a critical role in tumor progression and host immune response. Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have been reported as prognostic factors in several malignancies. We explored the association of NLR and LMR with progression-free survival (PFS) and overall survival (OS) in underserved patients treated with immune checkpoint inhibitors (ICIs). Methods: A retrospective review of 141 cancer patients treated with ICIs was conducted at Cook County Hospital, Chicago. Clinical and pathologic factors were recorded prior to start of ICIs. Cox regression analyses were conducted to correlate these factors with PFS and OS. Hazard ratios with 95% confidence intervals (CI) were obtained. Results: The study included 38% Afro-Americans, 31% Hispanics and 26% Caucasians. Median age was 58 years and 69% were males. Mean BMI and BSA were 24.6 kg/m2 and 1.6 m2, respectively. Primary cancer diagnoses were non-small cell lung cancer (35.5%), melanoma (19%), head and neck cancer (18%), renal cancer (11%), small cell lung cancer (8.5%) and others (8%). Type of ICI included Nivolumab (59%), Pembrolizumab (18%), Ipilimumab (7%), Ipilimumab with Nivolumab (14%) and Atezolizumab (2%). ICI therapy was given as first-line (17%), second-line (59%), third-line (16%), and beyond (8%). PD-L1 status was not available for any of the patients. Median NLR and LMR were 3.4 and 2.3. Median OS was 134 months (95% CI 49-219). Median PFS was 15 weeks (95% CI 13-17). Progression was documented in 64% patients and 27% patients died. Grade III-IV adverse events were reported in 8% patients. NLR (PFS: P = 0.652, OS: P = 0.899) and LMR (PFS: P = 0.938, OS: P = 0.596) did not predict PFS and OS. Conclusions: Although several retrospective studies have reported prognostic utility of peripheral blood NLR and LMR in cancer progression and success of ICI, we did not find predictive significance of NLR and LMR in cancer patients treated with ICIs. Tumor tissue NLR and LMR may have better prognostic utility and should be explored in further studies.
Patient, clinician, and non-patient perceptions of surgical complications in ovarian cancer.
Authors: Rudy Sam Suidan, Charlotte C. Sun, Karen H. Lu, Sharon Hermes Giordano, Larissa Meyer
Journal: Journal of Clinical Oncology (2018)

e22159 Background: Little is known about how pts perceive surgical complications in ovarian cancer (OC). Our objective was to elucidate the perceptions of pts with OC, and assess if they differ from those of clinical providers and a control group of women without OC. Methods: Pts, clinicians, and controls were prospectively interviewed. 14 surgical complications were assessed using the visual analog scale, which was was used to calculate utilities (perceptions). These were scored on a 0-1 scale, where 0 represents death and 1 represents perfect health. An
Neck dissection rate in node positive human papillomavirus associated oropharyngeal carcinoma following chemoradiotherapy.
Authors: Sandro Porceddu, Howard Liu, Anne Bernard, Laura Tam, Robin Milne, Matthew C Foote, Margaret Louise McGrath, Bena Cartmill, Elizabeth Brown, Bryan H Burmeister, Benedict Panizza
Journal: Journal of Clinical Oncology (2018)

6067 Background: With results of chemo-radiotherapy de-escalation trials for Human Papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) pending, any reduction in toxicity may be offset by the increased need for post-therapy neck dissection (PT-ND) for suspected residual nodal disease. We report the rate of PT-ND and overall regional failure rate following standard radiotherapy (RT) with or without chemotherapy (chemo)RT in node positive HPV-associated OPC. Secondary objectives include estimated 5-year regional failure free survival (FFS), loco-regional FFS, distant metastatic FFS and overall survival (OS). Methods: Patients treated between Jan 2005-Jan 2016 on a pre-defined (chemo)RT protocol and 12-week restaging PET/CT (treatment package) with a minimum of 18 months follow up (FU) were analysed. Patients receiving concurrent chemo were prescribed high-dose cisplatin and 70Gy/7 weeks to gross disease. Those ineligible for cisplatin received weekly cetuximab. PT-ND was performed if residual nodal disease was suspected on the restaging scan with complete response at the primary site and no evidence of distant disease. Results: 343 patients were eligible. Median follow up was 60 months, with 302 (88%) alive at the close-out date. Median age was 59 (range, 21-89) yrs. The predominant AJCC/UICC 7th Edition (Ed) T- & N-stage were T2 (37.3%) & N2b (44.9%), respectively. The 8th Ed group staging were; Stage I-49%, Stage II-28% & Stage III–23%. Median RT dose was 70Gy (range, 66-70Gy) and 336 (95.6%) received systemic therapy. At the completion of the treatment package 4.6% (16pts) underwent a ND. 10 pts (62.5%) were pathologically positive. The overall regional failure rate was 6.4%. The estimated 5-year regional FFS was 93% (95% CI: 90.2-95.9), loco-regional FFS 90.6% (95% CI: 87.3-94.0) and distant metastatic FFS 86.9% (95% CI: 83.1-90.8). 5-year OS by stage were; I–93.4% (95% CI: 89.5-97.5), II–82.9% (95% CI: 75.3-91.3) & III–75.9% (95% CI: 66-87.3). Conclusions: Following the treatment package the ND rate was low and regional failure uncommon. These findings serve as a benchmark to assess the benefit of de-escalation trials, which may be offset by an increased need for PT-ND.
A 'melanoma mortality belt' of ten U.S. states with the highest melanoma mortality rates.
Authors: Alan Geller, Juliana Berk-Krauss, David Polsky, Jennifer Stein
Journal: Journal of Clinical Oncology (2017)

e21039 Background: To our knowledge, no study has looked at U.S. melanoma mortality trends by state. We sought to determine the ten states with the highest melanoma mortality rates (per white population) and those with the lowest, as well as any state-wide demographics that could account for these trends. Methods: State melanoma mortality rates were collected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and National Program for Cancer Registries. Data on state characteristics were collectied from the Area Health Resource File (AHRF) and the US Census Bureau. We used a regression model to determine associations between melanoma mortality and the state demographic context, such as median income, per capita income, unemployment rate, education level, and rural versus nonrural. We also examined the effect of access to health care resources by looking at density of dermatologists, density of primary care providers, and total number of hospitals. Results: We identified ten states concentrated across the central United States with the highest melanoma mortality rates. Per capita income was the only significant association for melanoma mortality rates (p = 0.0016, 95% CI 6.88 to 18.09). Median income, unemployment rate, education level, rural versus non-rural, health professional density, and unemployment rate were not associated with melanoma mortality rates by state. Conclusions: There exists a ‘melanoma mortality belt’ across the central United States made up of the ten states with the highest melanoma mortality rates. This trend could not be consistently accounted for by state demographics, even socioeconomic status traditionally thought to correlate with mortality. Only one significant association was seen between melanoma mortality rate and per capita income. Our preliminary findings highlight the multifactorial picture of geographic melanoma mortality inequalities in the U.S.
Clinical outcomes of early-stage ampullary carcinoma: KU Cancer Center experience.
Authors: Mohammed Al-Jumayli, Akshay Middinti, Anusha Chidharla, Ravi Kumar Paluri, Anup Kasi
Journal: Journal of Clinical Oncology (2018)

e16192 Background: Ampullary cancer (AC) is a rare GI malignancy. The management of the locoregional disease iscurative surgery.The role of adjuvant chemotherapy[CT] or combination chemoradiation[CRT] is not well established. We analyzed our institution’s experience in AC.Methods: From June 2006 to July 2016,54 patients with early stage AC were reviewed. Clinicopathological characteristics, PFS and OS were compared between the group who underwent surgery Vs. those who received adjuvant therapy after the surgery Results: The median age of the 54 patients [38(72%) males,15(27%)females] was 67(37-90). Most of patients were white 40(75%) with 5(3%) African American. 52%(28) have smoking history, alcohol abuse 20%(11) and history of pancreatitis 13%(7).In those with localized cancers9(16%)were not surgical candidates. Adjuvant treatment was administered in18(39%)[CT13(28%) CRT 5(11%)]The remaining28(61%) patients underwent surgery alone. A recurrence was noted in 40% of study group. Median OS of the cohort is 30ms with 5yr OS at 30%.Median PFS and OSfor surgery only group was50ms and 61 ms and for surgery + adjuvant therapy group was14ms and 32 months respectively. Compared to surgery alone, adjuvant CT or CRT had no statistically significant difference in terms of PFS(P = 0.56)or OS(P = 0.80). High risk features like peripancreatic extension(16%),perineural invasion(26%)Lymph node positivitivity(29%),Lymphovascular invasion (29% )showed a trend towards poor OS with HR of 1.8,1.6,1.4 and1.2 respectively but were not statistically significant. Conclusions: Despite potentially curative surgery for AC, the recurrence rate is high. In our study, adding adjuvant therapy was not associated with statistically improvement in the OS compared to surgery alone. The limitations of our study include single institution, retrospective study with small sample size. However, the Subgroups with high risk phenotypes such as histological subtypes, peripancreatic extension and Lymphovascular invasion are associated with benefit from adjuvant therapy. A trend in the statistical significance is observed and needs further validation in larger cohort.
Relapse-free survial and target identification to enhance response with neoadjuvant and adjuvant dabrafenib + trametinib (D+T) treatment compared to standard-of-care (SOC) surgery in patients (pts) with high-risk resectable BRAF-mutant metastatic melanoma.
Authors: Jennifer Ann Wargo, Rodabe Navroze Amaria, Peter A. Prieto, Miles Cameron Andrews, Michael T. Tetzlaff, Phillip Andrew Futreal, Patrick Hwu, Wen-Jen Hwu, Isabella Claudia Glitza, Hussein Abdul-Hassan Tawbi, Janice N. Cormier, Jeffrey Edwin Lee, Sapna Pradyuman Patel, Lauren Simpson, Elizabeth M. Burton, Roland L. Bassett, Merrick I. Ross, Jeffrey E. Gershenwald, Michael A. Davies, Scott Eric Woodman
Journal: Journal of Clinical Oncology (2017)

9587 Background: Targeted and immune therapies have dramatically improved outcomes in stage IV metastatic melanoma pts. These agents are now being tested in earlier-stage disease. SOC surgery for high-risk resectable melanoma (AJCC stage IIIB/IIIC), with or without adjuvant therapy, is associated with a high risk of relapse (~70%). We hypothesized that neoadjuvant (neo) + adjuvant treatment with D+T improves RFS in these pts. Longitudinally collected biospecimens from pts receiving this treatment were analyzed to identify candidate strategies to further improve outcomes. Methods: A prospective single-institution randomized clinical trial (NCT02231775) was conducted in BRAF-mutant pts with resectable Stage IIIB/C or oligometastatic stage IV melanoma. Pts were randomized 1:2 to SOC (Arm A) versus neo + adjuvant D+T (Arm B; 8 wks neo + 44 wks adjuvant). The primary endpoint was RFS. Tumor biopsies were collected at baseline, week 3, and at surgery for molecular and immune profiling (whole exome sequencing, gene expression profiling, IHC, flow cytometry). Results: 21 of a planned 84 patients were enrolled (Arm A = 7, Arm B = 14). Arms were well balanced for standard prognostic factors, and toxicity was manageable. RECIST response rate with neo D+T was 77%, and the pathologic complete response rate (pCR) was 58%. First interim analysis revealed significantly improved RFS in the D+T arm over SOC (HR 62.5, p &lt; 0.0001), leading to early closure to enrollment. Pts with a pCR at surgery had significantly improved RFS versus pts without pCR (p = 0.04) on neo D+T. Tumor profiling revealed incomplete MAPK pathway blockade and higher levels of CD8+ T cells expressing immunomodulators Tim-3 and Lag-3 in pts who did not achieve a pCR. Conclusions: Neo + adjuvant D+T is associated with a high pCR rate and markedly improved RFS over SOC in pts with high-risk resectable BRAF-mutant metastatic melanoma. pCR at surgery is associated with improved RFS. Tumor analyses reveal candidate targets for testing in future trials to enhance responses to neo D+T. Clinical trial information: NCT02231775.
Predictive impact of quality of life measurements in chemotherapy treated advanced pancreatic cancer patients at a single Canadian cancer institution.
Authors: Christina Kim, Quincy S. Chu, Konrad Fassbender, Sunita Ghosh, Jennifer L. Spratlin
Journal: Journal of Clinical Oncology (2016)

e21650 Background: Despite advancements in the treatment of advanced pancreatic cancer (APC), prognosis remains poor. With short survival despite aggressive chemotherapy regimens, maintaining quality of life (QOL) is paramount. Evidence suggests QOL may be a prognostic and predictive marker for clinical outcomes in poor prognosis cancers; we hypothesize this is the case in APC. Methods: Patients (pts) > 18 years of age with APC diagnosed between January 1, 2005 and December 31, 2010 and treated at a single Canadian institution were identified using the provincial cancer registry. QOL was assessed using a composite endpoint of clinical benefit, defined as an improvement in patient-reported pain, opioid consumption, ECOG performance status and/or weight. Best radiologic response, progression free survival (PFS) and overall survival (OS) were recorded. Results: Of 387 pts identified by the provincial cancer registry, 103 were seen in consultation and received chemotherapy. Median age was 64 (range 38-84); 58% were male and 66% had metastatic disease. At baseline, the majority of pts reported pain (80%), opioid use (61%) or weight loss (71%). Thirty five (34%) pts experienced a clinical benefit with chemotherapy, but only 6 (17%) of these pts had a radiologic response. The median PFS and OS were improved in pts who experienced a clinical benefit (6.6 months versus 4.6 months, p= 0.03 and 11.7 months versus 6.1 months, p< 0.0001, respectively). Conclusions: In pts with APC treated with chemotherapy, improvement in QOL as indexed by clinical benefit from chemotherapy, predicted for improved PFS and OS. However, it did not appear to be associated with radiologic response to chemotherapy. As such, we have undertaken a prospective study, using validated QOL assessment tools, to further investigate the prognostic and predictive significance of baseline and subsequent QOL scores in patients with APC receiving palliative chemotherapy.
Risk-stratified multidisciplinary ambulatory management of malignant bowel obstruction (MAMBO) program for women with advanced gynecological cancer.
Authors: Yeh Chen Lee, Stephanie Lheureux, Nazlin Jivraj, Catherine O'Brien, Stephane Laframboise, Lisa Michele Tinker, Toral Patel, Terri Stuart-McEwan, Pamela Savage, Alexandra Maria Easson, Jennifer Croke, Jenny Lau, Eran Shlomovitz, Tanya Chawla, Johane Allard, Sarah Buchanan, Pamela Ng, Katherine Karakasis, Amit M. Oza
Journal: Journal of Clinical Oncology (2017)

e18024 Background: Malignant bowel obstruction (MBO) in gynecologic oncology patients is associated with poor prognosis, debilitating symptoms and compromises quality of life. Management of MBO poses a clinical challenge with prolonged hospitalization. Evidence based guidelines for surgical intervention, use of chemotherapy, total parenteral nutrition or best supportive care in this patient population is lacking. Surgical correction may improve survival in selected patients. Retrospective analysis to assess impact of MBO show variable range of MBO-related admissions up to 60 days, and is associated with significant morbidity. Methods: A risk stratified MAMBO program for gynecologic patients has been implemented at Princess Margaret Cancer Centre to define a systematic approach for MBO management and build multidisciplinary consensus for personalized treatment of our patients. The program is novel and includes a nurse-led ambulatory management algorithm with an eHealth application designed to monitor bowel symptoms. A symptom-driven classification system has been devised to objectively define risk using a MBO management algorithm. Complex MBO cases are discussed in designated MBO rounds for consensus treatment recommendation. All patients with MBO are enrolled into a prospective database. Patients undergoing surgical procedures for MBO are consented for opportunistic tissue collection for translational research. MBO patient education materials have been developed to improve awareness and encourage proactive bowel symptom management. Results: Seventy nine patients have been followed through this risk stratified MAMBO program for ambulatory care over 6 months. The MBO program integrates diet, laxatives/stool softeners and drug therapy. Designated MBO rounds are now established for complex case discussion. A prospective MBO database will evaluate treatment and patient-reported outcomes. Conclusions: Risk stratified model of care for multidisciplinary MBO program facilitates decision-making between disciplines and optimize patient care in a vulnerable population with support for ambulatory care.
TCT-845 Clinical impact of low platelet count in patients with coronary arterial disease after percutaneous coronary intervention
Authors: Sangwoo Park, Sun Hack Lee, Tae oh Kim, Yong-Hoon Yoon, Sang Yong Om, Minsoo Kim, Sang-Cheol Cho, Hanbit Park, Kyusup Lee, Osung Kwon, Euihong Ko, Do-yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Soo-Jin Kang, Duk-Woo Park, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)