tbuckley/cabot-search huggingface dataset:
The role of maintenance strategy in metastatic colorectal cancer (mCRC): A systematic review and meta-analysis.
Authors: Mohamad Bassam Sonbol, Luke Mountjoy, Belal Firwana, Diana Almader-Douglas, Kabir Mody, Joleen Marie Hubbard, Mitesh J. Borad, Daniel H. Ahn, M. Hassan Murad, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2019)

3524 Background: In mCRC, induction combination chemotherapy with targeted agents is considered the mainstay of treatment. This is typically followed by maintenance therapy vs. observation which had been examined in various trials. However, it remains unclear how best optimize maintenance strategy. We aim to evaluate comparative effectiveness to support best maintenance strategy. Methods: We searched PubMed, Embase, and Cochrane CENTRAL for randomized controlled trials (RCT) evaluating different maintenance strategies in previously untreated mCRC patients (pts): observation (obs), bevacizumab (bev), fluoropyrimidine (FP), FP+bev, or continuing induction regimen (CTX). Outcomes of interest included OS and PFS. The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White’s multivariate meta-regression to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Results: Twelve trials at low risk of bias (5540 pts) were included. Network meta-analysis shows no benefit of CTX over obs in terms of PFS (HR 0.7; 95% CI 0.46-1.09) and OS (HR 0.95; 95% CI 0.85-1.07). Compared to obs, maintenance therapy shows PFS benefit (HR 0.58; 95% CI 0.43-0.77) with only a trend in OS (HR 0.91; 95% CI 0.83-1.009). All maintenance strategies (FP, FP+bev, and bev) show significant improvement in PFS over obs. On SUCRA analysis, maintenance treatment (FP or FP+bev) has the highest likelihood of achieving better PFS (67.1% for FP and 99.8% for FP+bev) and OS (81.3% for FP and 73.2% for FP+bev). Conclusions: A maintenance strategy with at least a FP with or without the addition of bevacizumab is preferred. However, given the lack of a clear OS benefit, obs is an acceptable alternative. Optimal maintenance strategies should be dependent on factors including patient preferences, cost and toxicities. [Table: see text]
BEATcc (ENGOT-Cx10/GEICO 68-C/GOG3030/JGOG1084): A randomized, open label, phase III study of cisplatin and paclitaxel chemotherapy with bevacizumab (CTx plus B) with or without atezolizumab (Atz) as first-line treatment for metastatic, persistent, or recurrent (m/r) carcinoma of the cervix (CCx).
Authors: Ana Oaknin, Laurence Gladieff, Nicoletta Colombo, Guillermo Villacampa, Mansoor Raza Mirza, Ugo De Giorgi, Leslie M. Randall, Munetaka Takekuma, Antonio González-Martín
Journal: Journal of Clinical Oncology (2019)

TPS5594 Background: The combination of CTx plus B is first line treatment for most patients (pts) with m/r CCx not amenable for local therapy based on GOG240 results. GOG240 regimen showed an improvement in overall survival (OS) compared to CTx alone: 16.8 vs. 13.3 months (HR 0.77, 95% CI 0.62–0.95, p = 0.007). However, further improvement in first line therapy outcomes is an unmet need. Immune-checkpoint inhibitors are breakthrough therapies in several tumor types, and their development in CCx is supported by a strong scientific rationale. Human papillomavirus infection (HPV) causes more than 90% of CCx cases. PD-L1 is a HPV biomarker and is found frequently up-regulated in CCx. Nivolumab and pembrolizumab (Pb) (anti-PD-1 antibodies) have shown response rates of 26.3% and 14.3%, respectively, in pretreated m/r CCx. This has led to the recent FDA approval of Pb in pretreated PD-L1+ m/r CCx. The BEATcc trial (NCT03556839) evaluates the addition of the anti-PD-L1 agent Atz to GOG240 regimen as first line treatment for m/r CCx, following the synergistic rationale between anti-VEGF agents and PD-1/PD-L1 blockade. Methods: Eligible pts: m/r CC with adequate organ function. Pts will be randomized 1:1 to either Arm A (control): C 50 mg/m2 + Tx 175mg/m2 + B 15 mg/kg (CTx plus B) i.v. D1 Q3W or Arm B (experimental): CTx plus B + Atz 1200 mg i.v. D1 Q3W. Stratification factors: prior chemo-radiation, histology and Chemotherapy backbone (CTx vs carboplatin-Tx). Treatment is planned until disease progression, unacceptable toxicity or withdrawal of consent. Pts with a complete response after ≥6 cycles or those with unacceptable CTx toxicity may be allowed to continue only on biologics therapy. An Independent Data Monitoring Committee will analyze the safety of the first 12 pts in the experimental arm completing 2 treatment cycles. The primary endpoint is OS. The study started enrolling in October 2018 and will enroll approximately 404 pts across Europe, Japan, and the US. Clinical trial information: NCT03556839.
Development of a comprehensive prognostic model of lymphedema risk for breast cancer survivors.
Authors: Jennifer Kwan, Petra Famiyeh, Jie Su, Wei Xu, Kenneth Yip, Fei Fei Liu
Journal: Journal of Clinical Oncology (2019)

e23083 Background: Lymphedema is a side-effect of cancer treatment affecting up to 1 in 5 cancer survivors. It is associated with life-threatening medical complications and higher medical costs. To facilitate early detection and treatment of lymphedema in high-risk patients, improved prognostic modeling is required. Methods: The study cohort comprised of female breast cancer survivors at the Princess Margaret Cancer Centre during 2016-18. Using lymphedema diagnosis as the end-point, the Cox proportional-hazards model was applied to patient, disease, and treatment-related parameters to assess performance of established and putative novel prognostic factors for lymphedema. Concordance index (C-index) and Kaplan-Meier analyses were used to evaluate prognostic performance. Results: A total of 176 breast cancer survivors were included in the preliminary analysis. On univariable analysis, traditional treatment-related risk factors for lymphedema (e.g. axillary lymph node dissection, number of lymph nodes dissected, use of radiotherapy) were significant (p &lt; 0.05). Additionally, other treatment-related factors (e.g. radiation boost, supraclavicular radiation), disease factors (e.g. tumor size, number of positive lymph nodes, cancer stage), and patient/biological factors (e.g. developing a surgical seroma) were significant (p &lt; 0.05). Multivariable analysis revealed one traditional treatment-related factor (i.e. number of lymph nodes dissected) and other treatment details (e.g. radiation boost, axillary/supraclavicular radiation) to be the most significant factors. Combining radiation treatment details with traditional treatment-related lymphedema risk factors improved the C-index from 0.609 to 0.710 and separated patients into high- and low-risk groups with 2-year lymphedema-free survivals of 26% (15-44%) and 85% (74-97%) respectively (p &lt; 0.001). Conclusions: Prognostication of lymphedema risk can be improved by considering radiation treatment details, including use of radiation boost and site of radiotherapy. Biological factors, such as developing a surgical seroma, may reveal predisposition towards edema. Validation on an independent data set is being completed. Prospective validation is also required.
Access to care and financial burden for patients with breast cancer in Ghana, Kenya, and Nigeria.
Authors: Majid Twahir, Rasaaq Adisa Oyesegun, Joel Yarney, Andrew Gachii, Clement Edusa, Chukwumere Nwogu, Gitangu Mangutha, Philip Anderson, Emmanuel Benjamin, Borna Müller, Charles Ngoh
Journal: Journal of Clinical Oncology (2019)

6562 Background: Breast cancer is the most frequently diagnosed malignancy and the most common cause of cancer-related death in women in Ghana, Kenya, and Nigeria. We evaluated healthcare resource use and financial burden for patients treated at tertiary cancer centers in these countries. Methods: Records of breast cancer patients treated at the following government/private tertiary centers were included – Ghana: Korle-Bu Teaching Hospital and Sweden Ghana Medical Centre; Kenya: Kenyatta National Hospital and Aga Khan University Hospital; Nigeria: National Hospital Abuja and Lakeshore Cancer Center. Patients presenting within a prespecified 2-year period were followed until death or loss to follow-up. Results: The study included 299 patient records from Ghana, 314 from Kenya, and 249 from Nigeria. The use of common screening modalities (eg, mammogram, breast ultrasound) was &lt; 45% in all 3 countries. Use of core needle biopsy was 76% in Kenya and Nigeria, but only 50% in Ghana. Across the 3 countries, 91-98% of patients completed blood count/chemistry, whereas only 78-88% completed tests for hormone receptor and human epidermal growth factor receptor 2 (HER2). Most patients underwent surgery: mastectomy (64-67%) or breast-conserving Most patients in Ghana and Nigeria (87-93%) paid for their diagnostic tests entirely out of pocket (OOP) compared with 30-32% in Kenya. Similar to diagnostic testing, the proportion of patients paying OOP only for treatments was high: 72-89% in Nigeria, 45-79% in Ghana, and 8-20% in Kenya. Among those receiving HER2-targeted therapy, average number of cycles was 5 for patients paying OOP only vs 14 for patients with some level of insurance coverage. Conclusions: Patients treated in tertiary facilities in sub-Saharan African countries lack access to common imaging modalities and systemic therapies. Most patients in Ghana and Nigeria bore the full cost of their breast cancer care, suggestive of privileged financial status. Access to screening/diagnosis and appropriate care is likely to be substantively lower for the general population.
Use and impact of chemotherapy-free intervals in metastatic colorectal cancer in routine practice.
Authors: Amin Kay, Lingsong Yun, Nathan Taback, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

6535 Background: Several randomized trials have shown that chemotherapy-free intervals (CFIs) may reduce toxicity without compromising survival in patients with metastatic colorectal cancer (mCRC) treated with non-curative intent. However, uptake and outcomes of this approach in routine practice are unknown. We performed a population-based study of the patterns of use of CFIs and their impact on survival and toxicity among patients treated with first-line intravenous (IV) chemotherapy in Ontario, Canada. Methods: The Ontario Cancer Registry was linked with several other administrative databases to identify patients with colorectal cancer who started first-line IV chemotherapy between 2007-2009. A patient was considered to have had a CFI if more than 56 days elapsed between two chemotherapy billing claims. Survival of patients who had at least one CFI was compared to those who did not using Cox regression stratified by duration of treatment and adjusted for age, sex and Charlson comorbidity score. Analysis was performed separately for each type of first line treatment: Irinotecan (IRI), Irinotecan plus Bevacizumab (IR+B), and Oxaliplatin (OX). Toxicity was estimated by calculating the rate of emergency department visits and hospitalizations (adjusted for time on treatment) between those who did and did not have chemo breaks. Results: Between 2007-2009, 1,989 patients started first-line chemotherapy for mCRC in Ontario (22.6% IRI, 47.9% IRI+B, 29.5% OX). 489 (24.6%) had at least one CFI (14.9% IRI, 33.2% IRI+B, 18.1% OX). The median duration of first line treatment was 205 days (IQR 107-366 days). The median duration of the first CFI was 127 days (IQR 90-234 days). In multivariate models stratified by duration of treatment, CFIs did not have a negative effect on survival in either of the 3 treatment groups (HR: 0.62 IRI, 0.90 IRI+B, 0.51 O). Toxicity was lower in patients who had at least one CFI (12.6 vs 16.8 ER visits or admissions per person-month, p=0.036). Conclusions: Chemo-free intervals are used in routine practice in Ontario, and are associated with lower toxicity, without any apparent evidence of negative impact on survival.
Immune gene expression and bayesian network analysis in advanced non small cell lung cancer (NSCLC) patients treated with immunotherapy.
Authors: Sara Baglivo, Fortunato Bianconi, Francesca Romana Tofanetti, Biagio Ricciuti, Lorenza Pistola, Annamaria Siggillino, Maria Sole Reda, Clelia Mencaroni, Maria Francesca Currà, Valeria Teti, Giulio Metro, Guido Bellezza, Vincenzo Minotti, Fausto Roila, Vienna Ludovini
Journal: Journal of Clinical Oncology (2019)

e20693 Background: Immune checkpoint inhibitors (ICIs) have revoluzionized the therapeutic paradigm for different types of cancer including NSCLC. Clinical benefit, however, is limited to a minority of patients. The only adopted predictive biomarker, PD-L1 IHC testing, suffers from some limitations. A better understanding of biomarkers associated with response to ICIs is needed. Here, we studied immune gene expression profile and association with clinical response to immunotherapy in advanced NSCLC patients (pts) treated with ICI. Methods: A total of 37 Formalin-fixed, paraffin-embedded (FFPE) samples from advanced NSCLCs were analyzed by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) (ThermoFisher Scientific) to measure the expression level of 395 genes associated with 36 functional groups including checkpoint pathways, lymphocyte regulation and cytokine interactions, using the Ion Chef and Ion Torrent PGM. Gene level differential expression analysis were performed with the Torrent Suite and Transcriptome Analysis Console (TAC) 4.0 Software. Gene network analysis based on Bayesian algorithm was performed by GeneMANIA database querying with the genes selected through mRNA expression analysis. Results: Among 37 FFPE samples only 18 showed more than 300 OIRRA detectable target genes. In this subgroup, gene expression analysis revealed 7 genes (CCR2, CRTAM, FASLG, SELL, TIGIT, TNFRSF4, and TP63) up-regulated and one gene (CXCL8) down-regulated (p-value &lt; 0.05) in ICI-responders compare to ICI-no responders. Bayesian enrichment computational analysis of the eight gene expression signature showed a more complex network which involves other 10 genes (SIRPG, GZMK, XCL2, CD8A, CD2, IFNG, SIT1, TAGAP, PTPRC and GZMH), correlated with different functional groups. Three main immune-pathways were identified (p &lt; 0.01) (T cell activation, leucocyte activation and migration) involving TIGIT, TNFRSF4, CCR2 and CXCL8 genes among the gene expression signature identified. Conclusions: Our results revealed an immune response gene expression signature of 8 genes differentially expressed between ICI and ICI-no responders. Cancer systems biology analysis approach strengthen our findings identifying an immune molecular network and confirm the correlation of the gene expression signature with relevant immune regulatory functions. If validated, our results may have an important role for the development of a robust test to select patients properly and predict immune response to enable precision immunotherapy.
Pulmonary F-18 FDG uptake of non-tumor area in lung cancer patients to provide risk stratification in postoperative acute exacerbation of interstitial lung disease.
Authors: Takashi Yamamichi, Yoshihisa Shimada, Yojiro Makino, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Norihiko Ikeda
Journal: Journal of Clinical Oncology (2019)

e13165 Background: The incidence of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is higher than the general population. In IPF patients with lung cancer, postoperative acute exacerbation (AE) is considered a fatal comorbidity. This study aimed to investigate whether FDG-PET/CT can be used to assess the risk of postoperative AE of IPF and severe respiratory adverse events (SRAE),which are defined as grade 3a or more severe respiratory complications such as AE, bacterial pneumonia, empyema, and bronchial fistula based upon Clavian-Dindo classification. Methods: We identified 822 patients with lung cancer who had preoperative FDG-PET/CT and subsequent pulmonary resection from July 2012 to July 2018. We reviewed the patients’ clinical records and transferredthe preoperative FDG-PET/CT images of each patient to SynapseVincent system (Fujifilm Corporation, Tokyo, Japan) for measuring SUV value of the lung.Inevery case, both SUVmax of main tumor (tumor-SUVmax) and non-lung tumor part (NLT-SUVmax) were measured. Univariate and multivariate analyses were performed for exploring significant parameters associated with AE and SRAE. Results: The cohort in this study consisted of 460 men and 362 women (mean age 67.9 ± 10.1 years; range 23–87). SRAE was observed in 35 (4.2%) patients including those with AE (n = 16, 1.9%). NLT-SUVmax and presence of IPF on CT were the independent predictive factors for both AE and SRAE. The receiver operating characteristic (ROC) area under the curve (AUC) of significant factors associated with AE and SRAE was measured, and cut-off levels on ROC curves for significant parameters associated with AE and SRAE were 1.69 and 1.55, respectively. The risk rates for the incidence of AE and SRAE according to NLT-SUVmax and chest CT findings were 19.0 % and 30.2% of the patients with positive IPF on CT and NLT-SUV max ≥1.69. Conclusions: NLT-SUVmax was the independent predictor of the incidence of AE and SRAE for patients who underwent pulmonary resection. FDG/PET-CT can be used in routine clinical practice to identify high-risk individuals for AE who require careful and intensive observation after pulmonary resection and that can facilitate clinical decision-making.
Accounting for Height in an Analysis of Body Fat and Breast Cancer Risk
Authors: Kevin J. Lee
Journal: JAMA Oncology (2019)

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Tumor mutational burden (TMB) and response rates to immune checkpoint inhibitors (ICIs) targeting PD-1, CTLA-4, and combination.
Authors: Arsen Osipov, Aleksandra Popovic, Alexander Hopkins, Garrett M. Frampton, Lee A. Albacker, Nilofer Saba Azad, Daniel A. Laheru, Lei Zheng, Elizabeth M. Jaffee, Mark Yarchoan
Journal: Journal of Clinical Oncology (2019)

2578 Background: ICIs targeting PD-1/L1 and/or CTLA-4 have activity against many different cancers. We and others have previously shown that a higher TMB, a surrogate for an increased number of expressed tumor neoantigens, is an important biomarker for response to anti-PD-1/L1 monotherapy. Whether the relationship between the TMB and response to ICIs extends beyond anti-PD-1/L1 is unknown. Methods: We identified 30 major solid tumor types for which TMB has been described using a genomic profiling assay performed by Foundation Medicine. We conducted searches of MEDLINE (from Jan 1, 2010 to Jan 20, 2019), as well as abstracts presented at ASCO, ESMO, AACR Annual Meetings 2010-2018 to identify the objective response rate (ORR) for anti-PD-1/L1, anti-CTLA-4 and combination anti-PD-1/L1 plus anti-CTLA-4, in each of these cancer types. We pooled the response data from the largest published studies that evaluated the ORR. We excluded studies that; enrolled &lt; 10 evaluable patients, investigated ICI therapies in combination with other agents, and studies that selected patients based on immune-related biomarkers. Across tumor types, median TMB was compared to ORR utilizing the coefficient of determination (r 2 ) derived from simple linear regressions. Results: TMB is strongly associated with response to anti-PD-1/L1 monotherapy (n = 8798, r 2 = 0.4704, p &lt; 0.001), and combination anti-PD-1/L1 plus anti-CTLA-4 (n = 2280,r 2 = 0.4082, p = 0.004). Available ORR data were more limited with CTLA-4 monotherapy and the relationship between ORR and TMB did not meet statistical significance (n = 1377, r 2 = 0.2606, p = 0.1086). The additional ORR benefit of adding a CTLA-4 inhibitor to anti-PD-1/PDL1 therapy increased with increasing TMB. In tumor types with a lower TMB ( &lt; 10 mutations/MB), combined ICI therapy led to an average improvement of 5.5% in ORR over PD-1/L1 monotherapy, versus 21.8 % ORR improvement in high TMB tumors (≥10 mutations/MB). Conclusions: A strong relationship exists between TMB and clinical activity of both PD-1/L1 monotherapy and combination ICIs with PD-1/L1 plus CTLA-4. The clinical benefit of adding anti-CTLA-4 to anti-PD-1/L1 is greatest in high TMB tumors and limited in low TMB tumors.
Staccato pulse interleukin-2 (IL-2) in metastatic melanoma (MM) previously treated with checkpoint inhibitors (CPI).
Authors: Walter Quan, Leah I Gutierrez, Kyle Quan, Francine Marie Quan
Journal: Journal of Clinical Oncology (2019)

e21022 Background: The CPI ipilimumab, nivolumab, and pembrolizumab have been adopted into common use for patients (pts) with MM. While their clinical activity is undeniable, a substantial fraction of pts treated with these agents experience disease progression. Additional approaches are therefore needed. Intravenous IL-2 given via daily single intravenous infusions (pulses) has been developed to mitigate toxicity while maintaining anticancer activity against MM. Staccato pulse IL-2 is based on three prior observations. Daily IL-2 schedules have previously been demonstrated to induce Lymphokine Activated Killer cell (LAK) activity [Mitchell, 1989]. LAK generated by IL-2 then subsequently exposed to more IL-2 display enhanced cytotoxicity in vitro [Hank, 1990]. Increased numbers of LAK are seen in pts with melanoma treated with daily IL-2 [Quan, 2011]. Methods: In this retrospective study, ten pts with MM were treated with IL-2 18 Million IU/M2 intravenously over 15-30 minutes on days 1-3 and 21.6 Million IU/M2 intravenously over 15-30 minutes on day 5 on an outpatient basis. Cycles were repeated every 3 weeks. Results: Characteristics: 8 females/ 2 males, median age-56 (range: 21-74), median ECOG-1 (0-1); common disease sites: lymph nodes (12), subcutaneous (6), lungs (5), soft tissue (4). Prior CPI: Ipilimumab (8); Pembrolizumab (5); Nivolumab (2). Common toxicities: nausea/emesis (8), myalgia/arthralgia (5), sinus/catarrhal symptoms (5), fatigue (5), and hypotension requiring intravenous fluids (5). No pts required hospitalization for toxicity related to therapy. Median number of cycles: 3 (2-8). Four pts have had partial responses (total response rate = 40%; 95% CI: 10-70%). The median duration of response exceeds 7.4+ months. One pt having had resolution of prior lung, lymph node, and peritoneal metastases (partial response of 24.5+ months) underwent surgical resection of the residual intraabdominal disease focus and is free of disease at 36.5+ months. Overall, responses have occurred in lung, lymph nodes, subcutaneous, bones, peritoneum, small bowel, and soft tissue sites. Conclusions: Staccato pulse intravenous IL-2 has activity in melanoma pts previously treated with CPI.