tbuckley/cabot-search huggingface dataset:
A novel approach for sentinel lymph node identification using fluororescence imaging and computed tomography lymphography in early-stage breast cancer patients.
Authors: Hajime Abe, Keiichi Yamazaki, Aya Tokuda, Masao Ogawa, Masayasu Kawasaki, Masao Kameyama
Journal: Journal of Clinical Oncology (2014)

e12025 Background: We had reported a novel technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection. This study investigated whether computed tomography-lymphography (CTLG) can distinguish SLN and the usefulness of SLNB by the combined use of ICG fluorescence method and CTLG. Methods: This study enrolled 82 patients with clinically node-negative breast cancer. Their mean age was 60.6 (ranged from 33 to 87) years. On the day before the operation, we obtained three-dimensional imaging from multidetector-row CT by volume rendering. Contrast agent was injected intradermally, the location of SLN was marked on the skin surface using a CT laser light navigator system. During operation, fluorescence images were obtained using the fluorescence imaging system. Results: This method was visually easy to identify the location of SLN on the axillary skin even in obese patients. Even with small skin incision, SLNs were easily detected by the fluorescence imaging combined CTLG. CTLG could visualize lymphatic flow and accurately identify SLN in 78 (95%) of 82 patients, whereas fluorescence imaging identified successfully lymphatic flow and SLN in all patients. Lymphatic flows of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.5, p<0.01). Ten patients (12%) were found to have lymph node metastases pathologically, and three of them had micrometastases of lymph node. In 4 patients without detected SLN by CTLG, there was no lymph node metastasis. We classified enhancement of SLN as “whole” and “partial”, in case of partial enhancement, the rate of metastasis was significant higher compared to the cases of whole enhancement (p<0.01). Conclusions: This combined navigation method of fluorescence imaging and CTLG revealed more easy and effective to detect SLN than fluorescence imaging alone. In addition, the information from CTLG may be helpful for the diagnosis of SLN metastasis. Enhancement of SLNs by CTLG. Metastasis(+) Metastasis(-) Whole 2 48 Partial 7 21 Not identified 1 3
Type of progression in patients treated with imatinib for advanced gastrointestinal stromal tumor (GIST): A study based on the EORTC-ISG-AGITG trial 62005
Authors: M. M. Van Glabbeke, J. Verweij, P. Casali, J. Zalcberg, A. Le Cesne, P. Reichardt, R. Issels, I. Judson, M. Debiec-Rychter, J. Blay
Journal: Journal of Clinical Oncology (2009)

10536 Background: Development of resistance in GIST patients responding to targeted agents is heterogeneous, and different types of mutations may be observed in different lesions of the same patient. Progressive disease (PD) is defined as increase in size of initial lesions, occurrence of new lesions, or both (RECIST): mixed progression (MXPD), were new lesions develop when old lesions are still responding could represent a different type of biological event. We evaluated the impact of progression type and time to first PD (TTP) on survival after progression (SAP) in a randomized phase III trial comparing two doses of imatinib as first line treatment of GIST in 946 patients. Methods: PD was classified into 5 categories: PD in old lesion without new lesions (PD-), and new lesions associated with CR (CR+), PR (PR+), NC (NC+) and finally PD (PD+); MXPD was defined as CR+ or PR+. We investigated the correlations between type of PD, baseline patients’ characteristics, imatinib dose, TTP and SAP with univariate (UVA) and multivariate (MVA) analysis. Results: Currently, 516 patients with PD have been radiologically documented. PD-, CR+, PR+, NC+, and PD+ were observed respectively in 47%, 2%, 10%, 8%, and 33% of the cases. MXPD was more frequent in patients without prior chemotherapy (15% vs 8%), or with a long TTP (0–6 m: 1%; 6–12 m: 8%; 12–24 m: 12%; 24–60 m: 19%; 60+ m: 25%). MXPD was less frequent in KIT exon 9 mutants (7%) and wild types (4%) than in KIT exon 11 mutants (17%) (UVA), but this is entirely explained by their shorter TTP (MVA). No other correlation was found with imatinib dose or baseline factors. SAP was shown to increases with TTP (P&lt;0.0001), and was independently (and adversely) affected by PD of old lesions and development of new lesions: when compared to PD- patients, TTP adjusted SAP hazard ratio for patients with new lesions were 0.28 (CR+), 1.07 (PR+), 1.32 (NC+) and 1.61 (PD+). SAP was longer after MXPD (UVA), but this is explained by their longer TTP (MVA). Conclusions: In GIST patients treated with imatinib, survival after first progression increases with time to progression and decreases with “severity” of progression. Mixed progressions occur later than other types of progression, and therefore lead to a longer further survival. [Table: see text]
A phase 1b trial of duvelisib, a PI3K-δ,γ inhibitor, in combination with obinutuzumab in patients with CLL/SLL previously treated with a Bruton’s tyrosine kinase inhibitor (BTKi).
Authors: James Stewart Blachly, Jennifer R. Brown, Jacqueline Claudia Barrientos, Nitin Jain, Virginia Kelly, Stephanie Garnick, Jill Rodstrom, Jennifer Sweeney, Shijie Tang, John C. Byrd
Journal: Journal of Clinical Oncology (2015)

TPS7100 Background: Abrogating B-cell receptor pathway signaling through BTK inhibition is an effective treatment strategy for CLL. However, some patients (pts) do not respond, or progress despite BTK inhibitor (BTKi) treatment. Duvelisib, an oral inhibitor of PI3K-δ and PI3K-γ, can reduce downstream PI3K signaling even in the setting of BTK C481S mutation, thus providing an alternative for attenuating CLL growth and survival signaling. Early clinical activity observed in a Phase 1 study of duvelisib monotherapy in a subset of pts previously treated with a BTKi, suggest further evaluation is warranted (Porcu, ASH 2014). Combining duvelisib with obinutuzumab may augment clinical benefit through both cell intrinsic and extrinsic mechanisms. This study (IPI-145-18; ClinicalTrials.gov: NCT02292225) was designed to identify a tolerable dose of duvelisib combined with obinutuzumab, and to evaluate the safety and efficacy of the combination in relapsed/refractory CLL/SLL pts previously treated with a BTKi. Methods: This is a Phase 1b, open-label, dose escalation, safety and tolerability study of duvelisib in combination with obinutuzumab in pts with CLL/SLL whose disease is refractory to or has relapsed while receiving a BTKi therapy. Dose escalation (DE) Cohort 1 will receive duvelisib 25 mg BID in combination with obinutuzumab at its approved dose and schedule. Dose escalation of duvelisib to 50 mg BID or 75 mg BID may occur based on evaluation of dose limiting toxicities. Sequenced administration may be explored if the DE of duvelisib cannot progress when treatments are administered concurrently. An expansion phase is planned to explore the optimal dosing regimen of duvelisib in combination with obinutuzumab. Approximately 64 pts will be enrolled at 5-6 US sites. The primary endpoints are dose-limiting toxicities (DE phase only), AEs, and safety laboratory changes. Secondary endpoints are overall response rate, duration of response, progression-free survival, overall survival, BTK mutation status, and pharmacokinetics. Response will be evaluated according to the modified IWCLL 2008 response criteria. Clinical trial information: NCT02292225.
Defining the index lesion for salvage partial gland ablation after radiation therapy for localized prostate cancer.
Authors: Arjun Sivaraman, Toshikazu Takaeda, Hebert Alberto Vargas, Samson Fine, James Andrew Eastham, Behfar Ehdaie
Journal: Journal of Clinical Oncology (2017)

105 Background: Our objective was to evaluate the impact of MRI and systematic biopsy characteristics to identify the index lesion for salvage partial gland ablation using tumor maps from whole mount slides of salvage radical prostatectomy (sRP) specimen. Methods: We identified 225 patients who underwent sRP between 2000 and 2014 and a tumor map was created from whole-mount slides in 77 patients. Among these patients, we selected men with a priori pre-treatment criteria considered eligible for PGA, including, biopsy proven unilateral disease concordant with a region of interest (ROI) on MRI, and excluding men with imaging suspicious for extra-capsular extension (ECE), seminal vesicle Invasion (SVI) or lymph node involvement (LNI). We describe the correlation between pre-treatment clinical characteristics and final radical prostatectomy whole mount specimen to select men eligible for PGA defined as hemi-gland ablation. Results: Among 77 patients with a tumor map of entirely-submitted and whole-mounted specimens, 15 patients were determined to be eligible for partial gland ablation based on pre-treatment clinical characteristics. The mean age was 60 years and median time from primary RT was 48 months. The median (IQR) tumor volume of the index lesion was 0.3 (0.4) cc. The location of the index lesion was determined to be the apex, mid-gland and base in 77%, 100% and 15% of patients, respectively. The median distance of the index tumor to the urethra was 0.5 (0.2) cm. The index tumor was confined to one lobe and concordant to the biopsy pathology and MRI data in all 15 patients (100%). There was no ECE, LNI or SVI identified in the sRP specimens. To account for those patients who did not have a tumor map of the whole-mount specimen, a sensitivity analysis was performed and determined that the clinical characteristics of the 77 patients with tumor maps were comparable to the entire 225 sRP cohort. Conclusions: Clinical characteristics guided by biopsy findings and MRI data can be used to select men for PGA with recurrent localized prostate cancer after radiation therapy and based on tumor maps from sRP specimen, we propose that salvage hemi-gland ablation including periurethral tissue is feasible.
SWOG S1404: A phase III randomized trial comparing high dose interferon to pembrolizumab in patients with high risk resected melanoma.
Authors: Kenneth F. Grossmann, Megan Othus, Ahmad A. Tarhini, Sapna Pradyuman Patel, John M. Kirkwood, James Moon, Vernon K. Sondak, Antoni Ribas
Journal: Journal of Clinical Oncology (2015)

TPS9085 Background: Current adjuvant treatment for patients with a surgically resected stage III-IV melanoma is limited to high dose Interferon (HDI) and pegylated interferon (pegIFN), which have shown limited but consistent benefits in RFS (HDI and pegIFN) and OS (HDI) in high-risk melanoma, while no other agents have been proven superior in randomized trials. Anti-PD-1 antibodies such as pembrolizumab (MK-3475) have shown unprecedented rates of durable tumor response in patients with metastatic melanoma with low rates of adverse events. S1404 is a Phase III randomized trial comparing the standard of care HDI to pembrolizumab in patients at high risk for recurrence and death after surgery. Methods: Patients age 15 or greater with Stages IIIA(N2), IIIB, IIIC and IV (M1a, b and c) are eligible. Patients with brain metastasis will be excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel lymph node positive disease. Prior therapy with PD-1 blockade or interferon are not allowed. Two treatment arms are assigned based on stratification by stage and PD-L1 staining status (positive vs negative vs unknown). Patients (n = 1,378) will be randomized 1:1 to either 1) interferon Alfa-2b 20 MU/m2/days 1-5 weeks 1-4, followed by Interferon Alfa-2b 10 MU/m2/d SC days 1,3,5weeks 5 -52, or 2) pembrolizumab 200 mg day 1, q 3 weeks for 52 weeks. Efficacy will be measured in terms of both overall survival and relapse free survival, with interim analyses planned for both endpoints at 50% OS information. Safety, pharmacokinetics, and quality of life data will also be studied.
BeyPro1: A phase II single-arm study for the treatment after recurrence of advanced melanoma patients harboring the <sup>V600</sup>BRAF mutation and pretreated with vemurafenib, with the association of vemurafenib plus fotemustine.
Authors: Paola Queirolo, Francesco Spagnolo, Virginia Picasso, Elena Tornari, Vincenzo Ottaviano, Laura Giorello, Ester Simeone, Antonio Maria Grimaldi, Marcello Curvietto, Domenico Franco Merlo, Paolo Antonio Ascierto, Paolo Bruzzi
Journal: Journal of Clinical Oncology (2014)

TPS9109 Background: BRAF-inhibitor Vemurafenib achieves high response rate and a statistically significant improvement in overall survival (OS) in patients (pts) with unresectable stage III and IV melanoma. However, clinical resistance to this agent eventually arises in most pts. In a Phase I study of Vemurafenib, among 48 pts with progressive disease (PD), 18 pts were treated beyond progression (TBP) > 30 days after local therapy of PD lesions: median OS had not been reached at a median follow-up of 15.5 months from initiation of Vemurafenib, with a median treatment duration beyond initial PD of 3.5 months. Conversely, in pts who were not TBP, median OS was 1.4 months (Kim et al. ASCO 2011). In a series of 112 patients treated with BRAF-inhibitors (Chan et al. ASCO 2013), 36/92 were TBP: median OS from commencement of BRAF-inhibitors in those TBP was longer than those not TBP (15.0 vs 6.5 months, p<0.001), as was OS from PD (7.4 vs 1.9 mo, p=0.001). These findings suggest that one possible approach to improve the prognostic outlook in pts progressing during Vemurafenib treatment may be continuing the drug in combination with chemotherapy: resistance is not caused by acquisition of secondary BRAF mutations but rather by up-regulation in some cell populations of other proliferative signals with the creation of heterogeneous cell populations partly resistant to BRAF inhibition, and a cytotoxic drug such as Fotemustine (FTM) might act on those proliferating clones. FTM was chosen because it has shown an effect on brain metastases: in a phase III study (Avril et al. JCO 2004) comparing FTM with dacarbazine, the median time of occurrence of brain metastases was longer in the FTM group (22.7 months) than in the dacarbazine group (7.2 months). Methods: Thirty pts progressing while on Vemurafenib were enrolled in the study between January and October 2013. The primary objective is to assess the activity of Vemurafenib plus FTM in pts harboring the V600BRAF mutation and recurred while on treatment with Vemurafenib. The primary endpoint is PFS. Treatment with FTM plus Vemurafenib will be continued until PD or unacceptable toxicity. Clinical trial information: NCT01983124.
In Reply
Authors: Nasser H. Hanna
Journal: Journal of Clinical Oncology (2006)

We read with great interest the recent article by Hanna et al, 1 in which they reported irinotecan and cisplatin (IP) regimen was not superior to the etoposide and cisplatin (EP) regimen for extensive-stage-disease (ED) small-cell lung cancer (SCLC), even though Noda et al 2 clearly showed the superiority of IP regimen over EP regimen.We previously fractionated the schedule of IP to obtain the synergistic effect of the two drugs and to reduce toxicities. 3 The recommended doses of irinotecan and cisplatin on days 1 and 8 were determined to be 50 mg/m 2 and 60 mg/m 2 , respectively.However, the phase II study for ED SCLC was stopped early because of poor outcomes in the interim analysis. 4 Despite the small number of patients in our study, the median survival time and 1-year survival rates were similar to those reported in the study by Hanna et al (Table 1).The delivered doses of irinotecan and cisplatin in their study were 1.8 times and 0.7 times as much as those of our study, respectively (Table 1).In comparison to the study by Noda et al, we should have modified fractionated administration by escalating the dose of irinotecan and reducing that of cisplatin to improve the outcomes.However, both irinotecan and cisplatin in the Hanna et al study showed more dose intensity than that reported in the Noda et al study.Hanna et al suggested that IP might therefore be a better regimen for Japanese patients.We considered fractionated administrations of IP to be inferior to the original schedules of IP (cisplatin on day 1 and irinotecan on days 1, 8, and 15) for not only American but also Japanese patients with ED SCLC based on the findings of our study.Another explanation for the negative results of the Hanna et al study might be due to salvage chemotherapy.More patients on the IP arm received subsequent treatment with etoposide (47.2% v 22.6%) whereas more patients on the EP arm received subsequent treatment with topoisomerase I inhibitors including irinotecan or topotecan (33% v 24.1%). 1 Noda et al did not describe the use of salvage chemotherapy, which might have affected the survival difference in both arms.Because chemotherapy with fluorouracil, leucovorin, and irino-tecan (FOLFIRI), followed by fluorouracil, leucovorin, and oxaliplatin (FOLFOX), had almost the same efficacy as that with FOLFOX followed by FOLFIRI in the treatment of advanced colorectal cancer, 5 IP followed by EP might therefore have had the same efficacy as EP followed by IP in the treatment of ED SCLC.To achieve a prolonged survival, the administration of all three active cytotoxic drugs (cisplatin, irinotecan, and etoposide) during the treatment course may thus be necessary.
Monotherapy with tenofovir disoproxil fumarate for multiple drug‐resistant chronic hepatitis B: 3‐year trial
Authors: Young‐Suk Lim, Yung Sang Lee, Geum‐Youn Gwak, Kwan Soo Byun, Yoon Jun Kim, Jonggi Choi, Jihyun An, Han Chu Lee, Byung Chul Yoo, So Young Kwon
Journal: Hepatology (2017)

Combination therapy has been recommended for the treatment of patients harboring multiple drug‐resistant hepatitis B virus (HBV). However, we recently demonstrated that monotherapy with tenofovir disoproxil fumarate (TDF) for 48 weeks displayed noninferior efficacy to TDF plus entecavir (ETV) combination therapy in patients with HBV resistant to multiple drugs, including ETV and adefovir. Nonetheless, whether prolonged TDF monotherapy would be safe and increase the virologic response rate in these patients was unclear. Among 192 patients with HBV‐resistance mutations to ETV and/or adefovir, who were randomized to receive TDF monotherapy (n = 95) or TDF/ETV combination therapy (n = 97) for 48 weeks, 189 agreed to continue TDF monotherapy (TDF‐TDF group) or to switch to TDF monotherapy (TDF/ETV‐TDF group) and 180 (93.8%) completed the 144‐week study. Serum HBV DNA &lt;15 IU/mL at week 48, the primary efficacy endpoint, was achieved in 66.3% in the TDF‐TDF group and 68.0% in the TDF/ETV‐TDF group ( P = 0.80). At week 144, the proportion with HBV DNA &lt;15 IU/mL increased to 74.5%, which was significantly higher compared with that at week 48 ( P = 0.03), without a significant difference between groups ( P = 0.46). By on‐treatment analysis, a total of 79.4% had HBV DNA &lt;15 IU/mL at week 144. Transient virologic breakthrough occurred in 6 patients, which was due to poor drug adherence. At week 144, 19 patients who had HBV DNA levels &gt;60 IU/mL qualified for genotypic resistance analysis, and 6 retained some of their baseline resistance mutations of HBV. No patients developed additional resistance mutations throughout the study period. Conclusion : TDF monotherapy was efficacious and safe for up to 144 weeks, providing an increasing rate of virologic response in heavily pretreated patients with multidrug‐resistant HBV. (H epatology 2017;66:772–783).
Long-term cardiac safety analysis of NCCTG (Alliance) N9831 adjuvant trastuzumab (H) trial.
Authors: Pooja Prem Advani, Karla V. Ballman, Travis J. Dockter, Gerardo Colon-Otero, Edith A. Perez
Journal: Journal of Clinical Oncology (2014)

603 Background: Significant improvement in disease-free and overall survival has been established with the addition of H to adjuvant chemotherapy. However, H may increase risk of cardiac dysfunction (CD) and warrants long-term evaluation. Methods: N9831 compared adjuvant doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (T) (Arm A) vs. ACàTàH (Arm B) or ACàTHàH (Arm C) in operable HER2+ breast cancer. Cumulative incidence of cardiac events (CE) (symptomatic CHF and definite/probable cardiac death) and left ventricular ejection fraction (LVEF) assessed by MUGA/ECHO were evaluated in women who proceeded to post-AC therapy. Risk factors for H-related CD were identified by Cox regression models. Results: 977 women with clinical and LVEF data beyond 5 years (yr) from study enrollment were included (Arm A=304; Arm B=346 and Arm C=327); median follow up: 6.6 yr. Median age: 50 yr (range, 22–82). Median LVEF at 6 yr: 61% (Arm A); 61% (Arm B) and 60% (Arm C). Absolute median LVEF decrease from baseline: 3.0% (Arm A), 2.5% (Arm B) and 3.0% (Arm C). 6-yr cumulative incidence of CE: 0.6%, 2.8% and 3.4% in Arms A, B and C (minimal difference from CE at 3 yr: 0.5%, 2.6% and 3.4%). Suspected cardiac deaths: 4 (Arm A); 1 (Arm B); 1 (Arm C). There was a statistically significant increase in risk of CE in Arms B (HR 2.6; 95% CI: 1.1–6.2) and C (HR 3.4; 95% CI: 1.4–8.0) vs A (P = 0.019). Associated with increased risk of CE in Arms B and C were age > 60 yr (HR 3.2; 95%: CI 1.5-6.8, P = 0.0019), LVEF (50-55%) at registration (HR 3.3; 95% CI: 1.1-9.6, P = 0.030), and use of antihypertensive medications (HR 2.3; 95% CI: 1.2-4.4, P=0.015). Race (P = 0.318) and BMI 25-29.9 (P = 0.1038) and >30 (P = 0.0735) were nonsignificant risk factors. Conclusions: 6-yr cumulative incidence of CE was higher by 2.8% in the H-containing arms vs control arm. We noted minimal difference in the cumulative incidence of CE beyond 3-yr (Perez, JCO 2008), suggesting that late development of CE with H is infrequent. Hence, H (in context of anthracycline and taxane-based therapy) continues to have a favorable benefit-risk ratio (5-yr absolute OS benefit: 3.5%; DFS benefit: 12.7%). Older age, lower registration LVEF and antihypertensive medication use were predictive of increased risk of CD with H.
Number of cycles of chemotherapy in patients with advanced non-small cell lung caner: Efficacy and relationship with histology.
Authors: Eduardo Richardet, Martin Eduardo Richardet, Nicolas Castagneris, Matias Nicolas Cortes, Perelli Laura, Matias Molina
Journal: Journal of Clinical Oncology (2012)

e18125 Background: Platinum based regimens are standard first-line treatment in patients with advanced non mall cell lung cancer. We intend to evaluate their effectiveness according to the number of cycles administered, and investigate whether histology is a predictor of benefit from a greater number of infusions. Methods: 124 patients with stage IV NSCLC were evaluated retrospectively. They were divided according to whether they made 4 or 6 cycles of chemotherapy. The schemes used were: Cisplatin / Gemcitabine and Carboplatin / Paclitaxel, at standard doses. We studied the efficacy in both groups according to the most common histologies (adenocarcinoma and squamous cell carcinoma). PFS (progression-free survival) and OS (overall survival) were calculated by the Kaplan-Meier curves and compared by the Log Rank Test. Results: Those who underwent 4 cycles had a PFS of 7.77 months and OS of 12.2 months vs. 8.64 and 10.8 months those who received 6 cycles (p = 0.47, p = 0.76). Within the subgroup with squamous histology (n = 43), PFS and OS were 7.38 and 13.38 months respectively in the group that received 4 cycles vs. 7.97 and 9.76 months in those receiving 6 (p = 0.70, p = 0.32 ). Within adenocarcinoma histology (n = 81), those who received 4 cycle, has a PFS of 8.17 months and they lived 11.56 month, vs 8.96 and 10.79 months for those receiving 6 cycles (p = 0.29, p = 0.88) Conclusions: In our population, a greater number of cycles showed no advantages in terms of progression-free survival or overall survival. Histology is not a predictive factor for deciding how many chemotherapy cycles administer.