tbuckley/cabot-search huggingface dataset:
Risk of hematological, gastrointestinal, and hepatic toxicities in patients with advanced renal cell carcinoma treated with everolimus: A meta-analysis of phase 3 randomized controlled trials.
Authors: Henry Palangdao Igid, Kyaw Zin Thein, Sriman Swarup, Anita Sultan, Fred L. Hardwicke, Nicholas C. D'Cunha, Lukman Aderoju Tijani
Journal: Journal of Clinical Oncology (2018)

e16553 Background: The mTOR signaling pathway is involved in the pathogenesis of many malignancies by regulating cellular metabolism, proliferation, and angiogenesis. Everolimus (E) was shown to have clinical benefit in renal cell carcinoma with notable toxicities. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of hematological, gastrointestinal (GI), and hepatic toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2018 were queried. Phase 3 RCTs that mention hematological, GI and hepatic toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: A total of 1860 patients were eligible. Studies compared E vs cabozantinib or placebo or nivolumab. The RR of all-grade side effects were as follows: anemia, 1.87 (95% CI: 0.95-3.68, p = 0.06); lymphopenia, 3.25 (95% CI: 1.57-6.72, p = 0.001); thrombocytopenia, 1.39 (95% CI: 0.25-7.58, p = 0.69); nausea, 0.99 (95% CI: 0.48-2.04, p = 0.97); vomiting, 1.08 (95% CI: 0.13-8.59, p = 0.93); diarrhea, 1.40 (95% CI: 0.34-5.68, p = 0.63); stomatitis, 4.08 (95% CI: 0.71-23.39, p = 0.11); dysgeusia, 1.27 (95% CI: 0.10-15.46, p = 0.85); elevated aspartate aminotransferase (AST), 0.99 (95% CI: 0.10-9.26, p = 0.99); and elevated alanine aminotransferase (ALT), 1.30 (95% CI: 0.09-17.20, p = 0.84). The RR of high-grade side effects were as follows: anemia, 2.75 (95% CI: 1.81-4.15, p < 0.001); lymphopenia, 3.25 (95% CI: 1.57-6.72, p = 0.001); thrombocytopenia, 1.39 (95% CI: 0.25-7.58, p = 0.69); nausea, 0.42 (95% CI: 0.009 -18.94, p = 0.65); diarrhea, 0.61 (95% CI: 0.10-3.56, p = 0.59); stomatitis, 5.30 (95% CI: 0.30-92.01, p = 0.25); elevated AST, 0.38 (95% CI: 0.05-2.51, p = 0.31); and elevated ALT, 0.31 (95% CI: 0.02-3.53, p = 0.35). Conclusions: Everolimus contributed to a significant increase in high-grade anemia and lymphopenia although there was no significant increase in GI toxicities compared to control arm.
P05.20 Laterality of hipoccampal metastases: MRI analysis of 260 patients with 2595 brain metastases
Authors: T Kazda, A Kuklova, R Belanova, P Pospisil, P Burkon, L Hynkova, P Slampa, J Sana, O Slaby, R Jancalek
Journal: Neuro-Oncology (2018)

Strategies for preservation of memory function in patients irradiated for brain metastases (BM) are currently widely investigated. Rare presence of BM within hippocampus (Hipp) enabled development of Hipp avoiding (HA) whole brain radiotherapy (WBRT). However, this HA zone are undertreated with increased risk of subsequent BM recurrence. Accumulating data are showing different post-radiotherapy changes in the left and the right hippocampus with a theoretical proposal of only unilateral (dominant - left) hippocampal sparing during WBRT. The aim of this retrospective study is to describe spatial distribution of BM on MRI in a cohort of 260 patients (2595 metastases) and to evaluate distribution separately in the left and right Hipp and in respective HA zones including evaluation of location of centre of metastatic mass (representing spatial location of original seed during metastasis grown). Consecutive patients with BM referred to radiotherapy from 2011 till 2014 were analyzed. For those with BM in proximity to Hipp, both Hipp were contoured (RTOG contouring atlas) and expansion of 5mm was performed to create HA zone. All BM in the proximity were delineated for recording of contact to Hipp or to HA zone. 260 pattients, mean age 57.8, most common primary diagnosis lung cancer, 51.9 % women. Median number of BM per patient was 3 with interquartile range 1–7, most commonly cerebellum and frontal lobes. BM within left and right temporal lobe were described in 23.5 and 23.9 % of patients. Overall, 7.7 % of patients developed BM within Hipp and 18.1 % within HA zone, representing 1.1 and 3.3 % of all BM, respectively. There was no statistically significant difference in the laterality of Hipp or HA BM. Left and right Hipp were involved in 4.6 and 5.6 % of patients (HA involvement in 11.5 and 10.4 % of patients, respectively). Left and right Hipp BM represented 0.5 and 0.6 % of all BM (HA zone BM 1.6 and 1.7 % of all BM). More patients presented with the centre of metastasis within left (15 patients) vs. right (6) HAZ reaching statistical significance. No difference between involvement of left and right hippocampus on MRI was retrospectively observed in large consecutive cohort of 260 patients. Incidence of hippocampal BM in our cohort was higher comparing to previous studies. Superiority of HA WBRT will be evaluated in ongoing phase III clinical trials. Higher presence of BM within left HAZ comparing to the right side, when location of centrum of BM was evaluated is hypothesis generating observation and warrants further research.
Clinicopathological features of program death ligand-1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer.
Authors: Akihito Kawazoe, Kohei Shitara, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Takayuki Yoshino, Atsushi Ohtsu, Atsushi Ochiai, Yosuke Togashi, Hiroyoshi Nishikawa, Toshihiko Doi, Takeshi Kuwata
Journal: Journal of Clinical Oncology (2017)

4040 Background: Recently, anti-programmed death 1 (PD-1) or its ligand (PD-L1) antibodies have shown promising activities in metastatic gastric cancer (MGC). However, little is known about detailed clinicopathological features of PD-L1 expression in patients (pts) with MGC. Methods: Pts with histologically confirmed MGC were eligible for this prospective observational study. PD-L1 expression on tumor cell (TC) or inflammatory cell (IC) and mismatch repair (MMR) were analyzed by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was detected by in situ hybridization. The expressions of tyrosine kinase receptors (RTKs) such as HER2, EGFR and MET and cancer genome alterations were also evaluated by IHC or next generation sequencing. Results: A total of 237 pts were enrolled from September 2015 to December 2016. Samples of 199 (84.0%) pts were obtained from biopsy. PD-L1 expression on TC and IC was positive in 27 (11.4%) and 167 pts (70.5%), respectively. One hundred and seventy-one pts (72.2%) had positive PD-L1 expression on either TC or IC. MMR deficient (D-MMR) and EBV was detected in 14 (6.9%, n = 203) and 14 pts (5.9%, n = 237), respectively. PD-L1 expression on TC was more frequently observed in pts with D-MMR (P &lt; 0.001) and KRAS mutation (P &lt; 0.001), while that on IC was more frequently observed in pts with EBV+ (P = 0.045), lymph node metastasis (P = 0.001), and lung metastasis (P = 0.045). In contrast, pts with peritoneal metastasis were associated with less frequent PD-L1 expression in IC (P = 0.003). A significant association was not observed between PD-L1 expression and RTKs expression or presence of other gene alterations. D-MMR was significantly associated with intestinal type (P = 0.026) and absence of liver metastasis (P = 0.022). PD-L1 expression on either TC or IC was not prognostic factor (hazard ratio; 0.92, P = 0.741). Seven pts with D-MMR and seven pts with EBV+ MGC were enrolled in clinical trials of anti-PD-1/PD-L1 antibodies. Conclusions: PD-L1 expression in MGC was associated with some clinicopathological features. Impact of these characteristics on efficacy of anti-PD-1/PD-L1 antibody warrants further evaluation.
Impact of integrating insulin like growth factor-1 (IGF-1) in model for end stage liver disease (MELD) scores on predicting hepatocellular carcinoma patients’ survival.
Authors: Reham Abdel-Wahab, Sahin Lacin, Ahmed S Shalaby, Manal Hassan, Lianchun Xiao, Jeffrey Morris, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2016)

4080 Background: The status of the liver reserve in hepatocellular carcinoma (HCC) affects patient’s survival. In clinical practice, models for end-stage liver disease (MELD) score is used to predict overall survival (OS). Our aim is to evaluate whether integrating IGF-1 can provide additional value to MELD and sodium (Na)-MELD scoring systems in predicting patients’ OS. Methods: Plasma IGF-1 was measured in both training (n = 310) and validation (n = 155) cohorts from MD Anderson Cancer Center. We created MELD-IGF and Na-MELD-IGF scores from training cohort then we validate our results. Cox models were used to determine the association of IGF-1 with OS after adjustment for MELD and Na-MELD. Harrell’s C-index and U-statistics were used to compare the predictive capacity of MELD, Na-MELD, MELD-IGF, and Na-MELD-IGF. Results: IGF-1 was significantly associated with OS after adjusting for MELD or Na-MELD in both cohorts. Patients with IGF ≤ 26ng/ml had significantly higher hazard ratio (HR) compared to patients with the same MELD or Na-MELD but with IGF-1 > 26ng/ml among the training cohort (Table 1). MELD-IGF score had a higher C-index (0.59 and 0.72) compared to MELD score (0.56 and 0.66) (P = 0.017 and 0.011), among training and validation cohort respectively. While, the C-index for MELDNa-IGF was 0.633 compared to 0.629 for MELDNa score in the training cohort, the C-index for MELDNa-IGF and MELDNa scores were 0.72 and 0.66 (P = 0.31 and 0.003) respectively in the validation cohort. Conclusions: Our study indicate that MELD-IGF score is a significant predictor for patients’ OS after being validated into two independent cohorts. Future studies are warranted for international validation of this score. Models Training cohort HR (95% CI) Validation cohort HR (95% CI) MELD and IGF MELD 1.08 (1.04 – 1.12) 1.12 (1.05 - 1.19) IGF-1 ( ≤ 26 vs > 26) 1.96 (1.45 – 2.66) 2.31 (1.39 – 3.86) MELD*IGF 1.197 (1.09 – 1.32) 0.92 (0.78 – 1.1) MELD-IGF 1.07 (1.05 – 1.09) 1.05 (1.03 – 1.07) MELDNa and IGF MELDNa 1.08 (1.06 – 1.11) 1.09 (1.04 – 1.14) IGF-1 ( ≤ 26 vs > 26) 1.93 (1.42 – 2.62) 2.35 (1.39 – 3.98) MELDNa*IGF 1.13 (1.06 – 1.2) 0.97 (0.86 – 1.09) MELDNa-IGF 1.07 (1.05 – 1.08) 1.04 (1.02 – 1.06)
Abstract 16795: Comparison of Success Rate, Procedural Factors, and Radiation Exposure for Coronary Angiography Between Right and Left Radial Approach: Korea Transradial Coronary Intervention Prospective Registry (KOTRI)
Authors: Jun-Won Lee, Young-Jin Youn, Soonchang Hong, Sung Gyun Ahn, Min-Soo Ahn, Jang-Young Kim, Byung-Su Yoo, Seung-Hwan Lee, Junghan Yoon, Sung Ho Her, KyooRok Han, Sang Sig Cheong, Byung Ryul Cho, Jang-Ho Bae, Seung-Woon Rha, Yun-Hyeon Cho, Jin-Bae Lee, Kwang Soo Cha, Hee-Yeol Kim, Min Su Hyon, John Seo, Jae Woong Choi, Keum-Soo Park, Myung Ho Jeong, Sang Wook Kim, Jae-Hwan Lee, Kyung-Soo Kim, Doo-Il Kim
Journal: Circulation (2015)

Introduction: The use of radial artery is gradually increasing because transradial approach have shown less mortality and bleeding complications compared to transfermoral approach. But, there is little known about the differences according to radial access site except for fluoroscopic time and learning curve. Hypothesis: We aimed to compare the success rate, procedural factors and radiation exposure according to radial access site in patients who performed coronary angiography (CAG). Methods: The study population was derived from TRI prospective registry from 20 institutes in Korea from Feb 2013 to Sep 2013. Exclusion criteria were patients with data missing≥30%, invalid data, less than 19-year old patients, patient received interventional treatment, and patient who performed CAG via femoral approach. A total of 3496 among 5779 patients was assessed for data analysis. Success rate for CAG, crossover rate, procedural factors, fluoroscopic time and fluoroscopic dose were compared between right radial (RR) and left radial (LR) approach. Results: Mean age was 62.9±11.6 years and male was 1974 patients (56.5%). The use or EMLA cream was higher in LR group (29.2% vs. 14.0%, p&lt;0.001). CAG with single catheter was similar between RR and LR group (14.5% vs. 15.1%, p=0.652). Success rate for CAG was higher in RR group (99.4% vs. 98.1%, p=0.001). Crossover rate was higher in LR group (1.9% vs. 0.6%, p&lt;0.001). Most common cause for crossover was puncture failure 0.3% vs. 1.2%, p=0.002). Puncture time and CAG time were faster in LR group (2.1±2.7 mins vs. 2.5±3.0 mins, p&lt;0.001; 104±7.4 mins vs. 11.3±8.7 mins, p=0.003). LR group showed lower fluoroscopic time, dose (3.5±3.6 mins vs. 4.9±6.6 mins, p&lt;0.001 ; 37.5±47.8 Gycm2 vs. 41.1±42.2 Gycm2, p&lt;0.001) and higher total contrast volume (84.8±41.1 mL vs. 77.4±33.9 mL, p&lt;0.001). Conclusions: In KOTRI analysis, success rate for CAG was higher in RR group, but radiation time and dose were lower in LR group. Most common cause of crossover was puncture failure.
Skin test results with common and melanoma antigens in metastatic melanoma patients being treated with intratumoral injections.
Authors: Max H. Cohen, Ronald B. Herberman (Dec.)
Journal: Journal of Clinical Oncology (2018)

e21602 Background: In a previous randomized prospective study in patients receiving intralesional (IL) dinitrochorobenzene (DNCB) or IL Bacillus Calmette-Guerin (BCG) we determined that serial in vitro phytohemagglutinin stimulation levels during treatment correlated with the patients’ clinical outcomes. The current evaluation attempted to determine which skin tests during treatment correlated with outcomes. Methods: All patients had progressive cutaneous and/ or subcutaneous melanoma satellitosis metastases, or in-transit metastases, without evidence of metastasis past regional lymph nodes. Patients had been randomized to repeatedly receive either IL BCG (9 patients), or IL DNCB (9 patients) intratumorally into their metastatic nodules. A ‘BCG worse outcome group’ consisted of 6 patients in whom distant metastasis was detected within 2 to 20 months, and who died within 9 to 24 months. A ‘BCG better outcome group’ consisted of 3 patients who were alive and in whom no distant metastases were detected after 12 to 39 months. Similarly, the intralesional DNCB patients were also retrospectively divided into two groups: A ‘DNCB worse outcome group' consisted of 6 patients in whom distant metastasis was detected within 5 to 11 months, and who died within 6 to 12 months. A ‘DNCB better outcome group’ consisted of 3 patients who were alive and in whom no distant metastases were detected after 8 to 20 months. All patients were serially skin tested, as possible, with Purified Protein Derivative antigen (PPD), Mumps antigen, Streptokinase/Streptodornase (SKSD), and inactivated melanoma extracts, using coded syringes. Results: In comparing the two ‘better outcome’ groups with the two ‘worse outcome’ groups, patients who had a positive reaction to melanoma extracts during intratumoral treatment appeared to fare better than those who did not. All patient groups tended to react positively to SKSD, a general sign of immune capability. Conclusions: Among the skin tests compared, testing with melanoma extract during treatment appeared to correlate best with clinical courses in patients undergoing intratumoral injections for progressive melanoma satellitosis or in-transit metastases.
Clinical features and survival outcomes in a prospective spontaneous regression (SR) protocol of renal cell carcinoma (RCC) and melanoma (M) patients.
Authors: Olumide B. Gbolahan, Neda Hashemi-Sadraei, Abass Conteh, Hristos Z. Kaimakliotis, Walter Storkus, Roberto Pili, Theodore F. Logan
Journal: Journal of Clinical Oncology (2018)

e16585 Background: There are multiple case reports of spontaneously regressing metastatic RCC and M patients but little information about the natural history of disease after regression has been documented. We present a series of patients with spontaneously regressing RCC and M followed prospectively after documentation of tumor shrinkage. Methods: In 2003, we obtained IRB approval for an observation protocol for patients with SR of metastatic RCC or M to collect clinical-pathologic data and blood specimens. We defined a spontaneous regression based on any reduction in tumor size that persisted for more than 8 weeks in the absence of systemic therapy. No systemic anti-tumor therapy was given if the SR was maintained. Clinical and radiologic follow up was done regularly and updated 01/29/2018. Time to documentation of regression was determined and overall survival (OS) from surgery/most recent progression to documented regression was estimated by the Kaplan-Meir Method. Results: Between 2003 and 2018, 19 patients with a SR of metastatic RCC (15) and M (4) were identified. Patient and tumor characteristics are as follows: all patients were white, median age 55 years (41-69), 32% female, 14 (73%) had biopsy confirmed metastasis. There was a 2:1 left-sided predominance of RCC (66% vs 33%) with 14 (93%) clear cell. Sites of RCC metastasis included distant lymph nodes (67%), lung (67%), liver (7%) and bone (20%). Two (13%) RCC patients received systemic cytokine therapy prior to nephrectomy. All had nephrectomy before SR was documented. 2 (50%) M patients progressed on adjuvant therapy prior to documentation of SR. The median time from nephrectomy to SR in RCC was 101 days (49-336) and median time from the diagnosis of metastases was 99 days (68-112) for M. Median OS for RCC was 56.3 months (3.1- 204.2) and for metastatic M was 175.6 months (119.1- 215.4). Five (33%) of the RCC and none of the M patients relapsed after documented SR. Median time to relapse after SR was 476 days (116-1100). Conclusions: While SR remains rare, it may occur within 3-4 months of diagnosis of metastatic RCC/M. In our cohort, it is associated with prolonged remission. Immunologic correlates are being explored
Use of PSA kinetics to determine CT-PET PSMA uptake in recurrent or metastatic prostate cancer.
Authors: Avishay Sella, Svetlana Kovel, Tal Sella
Journal: Journal of Clinical Oncology (2017)

e16561 Background: CT-PET PSMA has recently been approved to more accurately detect the extent of prostate cancer. Here we examined PSA level and kinetics (PSA doubling time-PSADT) as a predictor of positive up-take in patients evaluated for suspected recurrent disease. Methods: We retrospectively collected data on 75 patients evaluated by CT-PET PSMA. Mann-Whitney U test and student's T Test (SPSS 20) were applied to test for differences in median in PSA and PSADT level. PSADT was calculated by Memorial Sloan Kettering Cancer Center calculator. Results: Seventy five patients underwent CT-PET PSMA. Their median age was 71 (52-94) years. Uptake was detected in 61(81%) patients; 37 (49%) patients with metastatic disease (lymph nodes, bones, visceral) and 24 (32%) patients with only localized disease (prostate, prostatic bed after prostatectomy). Median Gleason 8 (6-10). CT-PET was positive in 56%, 80% and 96% of patients with PSA levels of ≤1, 1-2 and &gt; 2 ng/ml, respectively, and 86%, 91% and 78% of patients with PSADT 1-2, 3-6 and &gt; 6 months, respectively. Only median PSA levels were significantly associated with any uptake: 6.05 + 24.08 vs. 0.36 + 4.31 ng/ml, p &lt; 0.001. Only median PSADT was statistically associated with metastatic disease compared to only local disease: 7.2 + 14.86 vs. 20.3 + 35.48 months, p &lt; 0.001. Similar results outcome were obtained using student's t-test (data not shown). Gleason score did not predict for CT-PET PSMA outcome. Conclusions: The decision to perform CT-PET PSMA in prostate cancer patients suspected to have recurrent or metastatic disease should be based on PSA levels. PSADT is an independent marker for positive metastatic uptake.
Impact of iron deficiency in patients with hepatocellular carcinoma: Data from the nationwide inpatient sample from 1999-2014.
Authors: Erika Correa, Stuthi Perimbeti, Mariola A. Vazquez Martinez, Maneesh Rajiv Jain, Kristine Marie Ward, David Lane Topolsky, Pamela A. Crilley, Michael Styler
Journal: Journal of Clinical Oncology (2018)

e18751 Background: Iron deficiency anemia (IDA) is a common condition in cancer patients (pts) and can have a deleterious effect on their outcomes. Pts with hepatocellular carcinoma (HCC) often have cirrhosis, hypersplenism, and marrow synthetic dysfunction. We assessed how IDA impacts hospital cost (HC), length of stay (LOS), and inpatient mortality (IM) in this population. These metrics were divided into teaching vs. non-teaching (NT) institutions. Methods: We analyzed data from the Healthcare Cost and Utilization Project’s National Inpatient Sample, from 1999 to 2014 using the ICD-9 code for HCC in the primary diagnosis field. IDA was listed as secondary diagnosis. The prevalence of IDA, total HC, LOS, and IM were compared and further divided into teaching vs. NT institutions. Chi-square test and Cox regression model were used. Results: 46335 admissions (weighted N = 228881) with HCC were identified from 1999 to 2014. Of these, 882 (weighted N = 3911) had IDA.Comparing IDA to those without, HC was higher, $50714 vs. $48213, and LOS was longer, 7.2 days vs. 6.5 days (p = 0.06). IDA IM was higher, 13.7% vs. 6.9%. After controlling for age, race, and comorbidities, HCC pts with IDA had a 133% increased risk of IM, 95% CI (1.97, 2.52). P < 0.0001 for above metrics. 31156 admissions (weighted N = 154954) with HCC were admitted to teaching institutions, and 61039 (weighted N = 12594) to NT institutions. 479 pts with IDA (weighted N = 2384) were admitted to teaching institutions and 247 (weighted N = 1199) admitted to NT institutions. In comparing teaching institutions to NT, HC was higher, $42804 vs. $53579 (p < 0.0001), and LOS was longer, 7.3 days vs. 6.8 days (p = 0.06). IM was higher, 8.5% vs. 5.6%, at teaching institutions (p < 0.01). Conclusions: HCC incidence and mortality rates have been increasing in the USA for over 35 years. Pts admitted with HCC and IDA demonstrated higher HC and mortality. Intriguingly, increased LOS was not significant, though demonstrated a trend. The same trends and significance were found in teaching institutions. This may be due to the higher acuity of pts seen in teaching institutions. Early identification and treatment of IDA may have a beneficial impact on HC, LOS, and overall IM in HCC pts.
Procedure-Specific Risk Prediction for Recurrence in Patients Undergoing Lobectomy or Sublobar Resection for Small (≤2 cm) Lung Adenocarcinoma: An International Cohort Analysis
Authors: Sarina Bains, Takashi Eguchi, Arne Warth, Yi-Chen Yeh, Jun-ichi Nitadori, Kaitlin M. Woo, Teh-Ying Chou, Hendrik Dienemann, Thomas Muley, Jun Nakajima, Aya Shinozaki-Ushiku, Yu-Chung Wu, Shaohua Lu, Kyuichi Kadota, David R. Jones, William D. Travis, Kay See Tan, Prasad S. Adusumilli
Journal: Journal of Thoracic Oncology (2018)