bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of lurbinectedin (PM01183) as single agent and in combination in patients with endometrial cancer.
Authors: Forster Martin David , Moreno Victor , Boni Valentina , Guerra Eva , Poveda Andres , Kristeleit Rebecca , Kahatt Carmen Maria , Lardelli Pilar , Lopez Vilarino Jose Antonio , Cuevas Nazly M , Soto-Matos Arturo , Calvo Emiliano 
Published: September 2018

5586 Background: Lurbinectedin (L) is a new anticancer drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment. Advanced endometrial cancer (EC) is an unmet medical need. Methods: Activity in EC patients was reviewed in 3 trials: a phase IB study of lurbinectedin combined with doxorubicin (L+DOX), a phase I study of PM combined with paclitaxel (L+TAX) and a phase II single-agent basket trial (L). Baseline characteristics, safety and efficacy were analyzed. Results: 97 patients were evaluated: 34 (2 cohorts) with L+DOX, 11 with L+TAX and 52 with L. Median age was similar in the 3 studies. Endometrioid was the most frequent histology. Median (range) of prior chemotherapy lines for advanced disease was: L+DOX, 1(0-2); L+TAX, 2(1-3); L, 1(0-2). Responses were observed in the 3 studies (see table). Main adverse event was myelosuppression (grade 3-4 neutropenia/thrombocytopenia/febrile neutropenia: L+DOX Cohort A, 94%/26%/40%; L+DOX Cohort B, 79%/10%/16%; L+TAX, 54%/0%/0%; L, 33%/6%/6%). Non-hematological toxicity was mostly grade 1-2: fatigue, nausea and vomiting, and transaminase increase. Conclusions: Lurbinectedin is active as single agent and in combination in patients with advanced EC, with remarkable activity in terms of response rate, duration of response and PFS when combined with doxorubicin. Safety was acceptable in L+DOX Cohort B, L+TAX and L, and myelosuppression was well managed. Clinical trial information: NCT01970540. [Table: see text]
Association of delayed adjuvant therapy and overall survival in early stage endometrial cancer.
Authors: Luo Leo , Shi Weiji , Zhang Zhigang , Tsai C. Jillian 
Published: September 2018

5590 Background: The primary treatment for early stage endometrial cancer includes definitive surgical staging procedure followed by adjuvant therapy in women with high risk of recurrence. The optimal interval time between surgery and adjuvant therapy is unclear. Methods: 349,404 patients with primary uterine carcinoma diagnosed from 2004 and 2012 were extracted from National Cancer Database (NCDB). Study population was limited to patients with FIGO 2009 stage I and II endometrial cancer with endometroid, mucinous, clear cell, or serous histology. Adjuvant therapy included radiation therapy, chemotherapy, or a combination. A binary variable of interval time between surgery and adjuvant therapy (“early” vs. “delayed”) was created by using the median time as a cutoff. Analysis of relationship between the interval time and overall survival was performed. Results: Final analysis included 118,373 early stage endometrial cancer patients who had definitive surgical treatment. Median age was 61 (interquartile range 55-69). 87,189 patients (74%) had stage IA disease, 21,573 (18%) patients had stage IB disease, and 9,611 (8%) patients had stage II disease. 28,824 (24%) patients received adjuvant therapy after surgery. The median time from surgery to adjuvant therapy was 1.6 months (interquartile range 1.3-2.2 months). Of the patients that received adjuvant therapy, 48% received intra-vaginal brachytherapy alone, 31% received pelvic external beam radiation, and 7% received a combination of chemotherapy and brachytherapy. There was a significant difference in overall survival in patients who received adjuvant therapy within 1.6 months from surgery and 1.6 months after surgery (Log-rank test, p = 0.04). Patients with advanced age, African-American or Hispanic race, and uninsured status or government-sponsored insurance were associated with delayed treatments. Conclusions: In this large retrospective review of early stage endometrial cancer patients, delayed time between surgery and adjuvant therapy is associated with worse overall survival. Further analysis will be performed to determine an optimal timing between surgery and adjuvant therapy.
Evaluation of systemic and local immune responses in patients with endometrial cancer.
Authors: Ore Martin , Romero Ignacio , Garcia-Casado Zaida , Zorrero Cristina , Illueca Carmen , Lopez-Guerrero Jose Antonio , Poveda Andres 
Published: September 2018

5594 Background: Several studies suggest that systemic immune response (SIR) and local immune response (LIR) have independent roles in multiple types of cancer. In endometrial cancer (EC), the correlation between SIR and LIR and its prognostic value remains unclear. Methods: A total of 146 EC patients (stage I-IV) who had undergone surgery from 2009 to 2015, were identified from a prospective institutional database. Lymphocyte/monocyte ratio (LMR) to represent SIR was calculated from preoperative blood samples. The presence of intratumoral and peritumoral infiltrating lymphocytes (TILs) on hematoxylin and eosin-stained slides was considered as a surrogate of LIR. LMR and TILs were correlated to pathological findings and survival outcomes (overall survival: OS, disease free survival: DFS). Results: A LMR cutoff value of 4.4 for survival was determined based on receiver operating characteristic (ROC) curve analysis. LMR high was significantly associated with endometrioid histology (p=0.03), lower grade (G1-2; p=0.003), < 50% myometrial invasion (p=0.01) and I-II stage (p=0.02). TILs were correlated with MSI-high (p<0.005), but not with LMR (p=0.3). Low LMR was associated with worse 5-year OS rates (64.5% vs 93.9%; p<0.01) and presence of TILs with better 5-years OS rates (72% vs 27%; p=0.04). On multivariate analysis (table 1) LMR, histology, stage and grade remained independent prognostic factors for OS (p=0.01). Using the combination of LMR and TILs, four groups with decreasing 5-years OS rates were identified: LMR-high/TILs+ (100%) > LMR-high/no-TILs (87%) > LMR-low/TILs+ (71%) > LMR-low/no-TILs (61%). Conclusions: In our series of resected EC patients, SIR (defined by LMR) constituted an independent prognostic factor for OS and LIR for DFS. We did not find any correlation between SIR and LIR, but the combination of both higher SIR and LIR showed better OS. [Table: see text]
Axillary management in early breast cancer: Surgeon attitudes in a population-based study.
Authors: Morrow Monica , Katz Steven J. , Jagsi Reshma 
Published: September 2018

561 Background: The ACOSOG Z0011 trial established the safety of omitting axillary dissection (ALND) for patients with 1‒2 sentinel node (SN) metastases having breast-conserving therapy (BCT) to reduce treatment-related morbidity. Little is known about surgeon uptake of this practice. Methods: Women with stage I and II breast cancer diagnosed between 7/13‒8/15 (n=3729) reported to the Los Angeles and Georgia SEER registries were surveyed about 2 months after diagnosis. All attending surgeons identified by the patients (n=489) were sent a questionnaire and 77% (n=377) responded. Pathology reports for SN positive patients are under review. Results: Mean surgeon age was 54 years, 25% were female, and median years in practice was 21. 49% and 63% endorsed ALND for Z0011 eligible patients with 1 or 2 SN macrometastases, respectively. Surgeons were classified as low (n=92), selective (n=178), or high (n=91) users of ALND based on responses to case scenarios with SN involvement ranging from isolated tumor cells in 1 SN (12% would do ALND) to macrometastasis in 3 SNs (92% would do ALND). 93% of high-use surgeons would perform ALND for any SN macrometastasis vs 40% of selective surgeons and 1% of low-use surgeons (p<.001). High-use surgeons were older, male, saw fewer breast cancer patients, and were less likely to discuss cases in tumor board (Table). High-ALND users were substantially less likely to endorse BCT margins of no ink on tumor (40%) than selective (63%) or low users (83%; p<.001). Conclusions: Wide variation exists in acceptance of Z011 results with one-quarter of surgeons endorsing routine ALND. Surgeons favoring ALND also endorse wider margins for BCT, suggesting an overall more aggressive surgical approach. Lower breast volume and lack of tumor board participation identify surgeons who should be targeted for educational interventions. [Table: see text]
Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection.
Authors: Ozmen Tolga , Lazaro Mesa , Zhou Yan , Vinyard Alicia , Avisar Eli 
Published: September 2018

563 Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure however requires microsurgical techniques. The aim of this study was to assess the efficiency of Simplified-LYMPHA (SLYMPHA) in preventing LE in a prospective cohort of patients. Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and December 2016 were included in the study. SLYMPHA is a slightly modified and simplified version of LYMPHA. It is performed by the operating surgeon performing the ALND. One or more lymphatic channels identified by reverse arm mapping are inserted using a sleeve technique into the cut end of a neighboring vein. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. Demographic, clinical, surgical and pathologic factors were recorded. The incidence of clinical LE was compared between ALND with and without SLYMPHA. Univariate and multivariate analysis were used to assess the role of other factors in the appearance of clinical LE. Results: 406 patients were included in the study. SLYMPHA procedure was attempted in 81 patients and was completed successfully in 90% of patients. Early complication rates were similar between patients who underwent SLYMPHA and who did not (4% vs. 4.13%; p = 0.948). Median follow-up time was 15±13.73 [1-32] months. Patients, who underwent SLYMPHA, had a significantly lower rate of clinical LE both in univariate and multivariate analysis (3% vs 19%; p = 0.001; OR 0.12 [0.03-0.5]). Excising > 22 lymph nodes and a co-diagnosis of diabetes were also correlated with higher clinical LE rates on univariate analysis, but only excising > 22 lymph nodes remained to be significant on multivariate analysis. Conclusions: SLYMPHA is a safe and relatively simple method, which decreases incidence of clinical LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.
Trends in rates of modified radical mastectomies and bilateral mastectomies in unilateral breast cancer.
Authors: Bulbul Ajaz , Braik Tareq , Rashad Sadaf , Mino Emilio Araujo , Bautista Adrianna , Khorsand-Sahbaie Masoud , Tripathy Debu ,   Kymera Physicians
Published: September 2018

569 Background: Women with unilateral breast cancer (BC) without genetic predisposition have a low risk for local and contralateral recurrence with breast conservation surgery (BCS) and adjuvant treatment. We aimed to study the pattern of surgical care across centers in rural New Mexico and its correlation to clinical outcomes. Methods: We retrospectively evaluated 533 patients with Stage 1-3 BC diagnosed between January 1989 to October 2015. Clinical Outcomes with BCS, sentinel lymph node dissection (SLND), simple mastectomy (SM), modified radical mastectomy (MRM) and Bilateral Mastectomy (BM) were studied. Descriptive statistics were performed to describe the proportion of surgery types. Predictors of clinical outcomes were evaluated by multivariate logistic regression. Results: Out of 533 patients, 510 (82%) had early stage (0-3) resectable BC. Among these, 48% (246/510) had either MRM (209/510) or BM (37/510). MRM was performed in 3% of stage 0 (6/209), 23% (49/209) stage I, 46%(97/209) of stage II and 27% (57/209) of Stage III patients. Overall, the rate of SLND was 42% among Early stage Breast cancer. Of 41 patients treated with bilateral mastectomy, 10 were positive for BRCA mutation, 6 for family history and 3 for contralateral disease. Median age of BM was 53 +12 y. The local recurrence rate was 8.8% (45/510), and metastatic recurrence rate was 15.5% (79/510). Lymphedema rate was 9.2% (47/510). Using MRM as reference, the Odds Ratio (OR) for lymphedema after BM and BCT were 2.15 (95% CI, 0.84-5.50) and 0.58 (0.28-1.22), respectively. With 9.6 years of median follow up, the predictive probabilities of lymphedema after BCT, SM, MRM and BM were 1%, 4%, 9% and 18%. The OR for local recurrence in women with BCT were 1.46 (95th C/I: 0.72-2.95), SM 0.27 (0.03-2.13), BM 2.06 (95th C/I:0.70-6.06). Conclusions: Less BCT and more aggressive procedures are being performed, and the latter is associated with more lymphedema. No significant differences were noted in local recurrences. Presence of a genetic mutation was not the sole indicator of BM’s in our patient population. There is a need for evidence-based shared decision-making and surgical management of breast cancer, especially in a rural community setting.
Effect of neoadjuvant chemotherapy regimen choice in patients with breast cancer with pathologic complete response.
Authors: Weiss Anna , Bashour Sami , Hsu Limin , Hess Kenneth R. , Thompson Alastair Mark , Ibrahim Nuhad K. 
Published: September 2018

570 Background: Breast cancer patients with a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize there is no difference in post-surgical recurrence free survival (RFS) between regimens used if pCR has been achieved. Methods: Breast cancer patients treated with NACT (using various regimens) between 1996 and 2011 who achieved pCR were examined, using a prospectively maintained electronic database. RFS was estimated by Kaplan-Meier method, differences between groups assessed using log-rank test. Cox proportional hazards regression analysis adjusted for age, menopausal status, stage, grade, tumor subtype, and adjuvant treatments. Results: 721 patients were identified: 40.4% Stage IIA, 21.2% IIB, 10.8% IIIA, 9.2% IIIB, 18.3% IIIC. 21.8% were hormone receptor positive (HR), 43.3% HER2 amplified, 32.7% triple negative. 50.9% of patients were treated with adriamycin-based chemotherapy plus taxane (adriamycin+taxane), 7.8% without taxane (adriamycin-taxane), 31.5% HER2 targeted therapy, and 9.8% provider choice. Median follow up was 7.4 years. There was no significant difference in RFS by treatment group (table 1). Adjusted RFS hazard ratios comparing each treatment to adriamycin+taxane were 1.25 (95% confidence interval 0.47-3.35) adriamycin-taxane, 0.90 (CI 0.37-2.20) HER2 targeted, and 1.28 (CI 0.55-2.98) provider choice. Conclusions: These data suggest that post-surgical RFS among patients with pCR is not significantly influenced by the type of NACT. Meta-analysis of randomized trial data should be explored to evaluate these findings. If RFS of pCR patients is not affected by regimen, this could allow flexibility in treatment choice and length. [Table: see text]
Improving pathological response in locally advanced triple negative breast cancer: Comparison between CbD and AC-T regimens.
Authors: Enriquez Daniel , Poma Nieto Nathaly , Fuentes Hugo Alejandro , Guerra Henry , Ruiz Mendoza Rossana Esther , Gomez Henry Leonidas 
Published: September 2018

585 Background: Pathological complete response (pCR) is a well-known surrogate for DFS and OS in triple negative breast cancer (TNBC). New approaches are being tested to increase pCR rate. We compared the standard of care (AC-T) vs Carboplatin/Docetaxel (CbD) for locally-advanced TNBC. Our objective is to determine whether CbD will increase the pCR rate, with PFS and OS as secondary objectives. Methods: A single arm phase II prospective trial with historical controls. 61 stage II-III TNBC patients were included between 2013-2014 at Instituto Nacional de Enfermedades Neoplasicas (Peru). 27 patients received Carboplatin 6AUC + Docetaxel 75mg/m2 q21d for 6cy, and 34pts, Adriamycin 60mg/m2 + Cyclophosphamide 600mg/m2 q21d for 4cy followed by weekly paclitaxel 80mg/m2 for 12 weeks. The Miller and Payne method was used to evaluate pathological response after definitive surgery. Results: Median age was 47 years, most patients were premenopausal (55.7%), median tumor size was 61 mm (T3=32.8%, T4=50.8%) and most patients had LN+ve (77%). There was a significantly greater tumor size in the CbD arm (mean 72.8 vs 52.2mm, p=0.007), no toxicity differences were noted. Only pCR was independently associated with OS/PFS on multivariate analysis. pCR was achieved in 37% (n=10) and 23.5% (n=8) in the CbD and AC-T groups, respectively (p=0.44). Partial pathological response was achieved in 37% (n=10) and 38.2% (n=13) patients in AC-T and CbD respectively. No characteristics were associated to pCR on logistic regression. At 2-year follow-up, all patients with pCR were alive and without recurrence, while patients with partial response achieved a 2-year PFS of 75% and, 2-year OS of 83.5%. The non-respondent group had the worse outcomes (2-year PFS: 32.7%, 2-year OS: 58.7%). The CbD group had a better 2-year PFS and OS (73.1% and 84%, respectively) than the AC-T group (59.3% and 71%, respectively), however no-statistical difference was found. Conclusions: CbD is an effective and promising neoadjuvant chemotherapy regimen for TNBC. Despite a larger mean tumor size in the CbD group, a non-significant trend towards higher pCR rate and longer PFS and OS was observed and warrants further exploration.
The role of PET for predicting nodal response in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy (CRT): Results of a prospective multicenter trial.
Authors: Schmitz Sandra , Van Maanen Aline , Rousseaux Laura , Andry Guy , Temam Stéphane , Dequanter Didier , Vergez Sebastien , Lallemant Benjamin , De Raucourt Dominique , Jegoux Franck , Hanin Francois-Xavier , Gregoire Vincent , Hamoir Marc 
Published: September 2018

6013 Background: Controversy about neck management after CRT in patients with LA HNSCC persists due to low accuracy of CT/MR to asses the neck. As already demonstrated (Mehanna, NEJM 374, 2016), PET is an alternative to planned neck dissection (ND) thanks to its high negative predictive value (NPV). However, no conclusion could be drawn for patients (pts) with equivocal response (e.g. suspicion of residual disease on CT/MR but negative PET) because pathologic confirmation was lacking. Methods: Multicenter, prospective, nonrandomized trial including pts with LA HNSCC of oral cavity, oro- hypopharynx, larynx, staged N1, N2, N3, treated with CRT and evaluated 12 weeks after CRT by overall assessment (OA): clinical examination (CE), PET and CT/MR. ND was performed in incomplete regional response based on at least 1 positive evaluation method. Pathologic analyses (HE and KI67) were performed on ND samples. Primary objective was to determine the NPV and accuracy of PET as a single examination in the post CRT nodal assessment. Primary outcome was 2-year regional recurrence free survival rate (RRFSR). Results: 264/318 pts included completed full treatment and had post CRT OA. Median follow up was 40 months. No ND was proposed in 119 patients because of a negative OA; 145 patients had ND. The presence of viable cells was reported in 27 ND (18.6%). Sensitivity, specificity, PPV, NPV, accuracy of OA were 90.0%, 49.6%, 18.6%, 97.5%, 54.2% vs 69.7%, 75.3.%, 28.8%, 94.6%, 74.6% for PET alone. Kappa coefficient was of 0.838, indicating an almost perfect agreement. In pts with negative OA, RRFSR was 61.3% vs. 56.6% in pts with positive OA and ND (p=0.45). Using post CRT assessment with PET alone, RRFSR in pts with negative PET was 63.0% vs. 48.8% in pts with positive PET (p=0.04). Using PET assessment alone, 65/145 ND (44.8%) could have been avoided without compromising RRFSR. Conclusions: NPV using PET alone is 94.6%. Post CRT evaluation using only PET would have resulted in considerably fewer ND without jeopardizing neck control. PET alone is more accurate and more discriminant for predicting pts outcome. Clinical trial information: NCT00634777.
Dose escalation of radiotherapy (RT) for locally advanced head and neck carcinomas treated with concomitant chemotherapy (CT) and RT: Results of the GORTEC 2004-01 randomized trial.
Authors: Bourhis Jean , Auperin Anne , Alfonsi Marc , Sun xu Shan , Rives Michel , Pointreau Yoann , Lafond Cedrik , Boisselier Pierre , Graff Pierre , Thariat Juliette , Tao Yungan 
Published: September 2018

6015 Background: Concomitant CT-RT is a well established standard of care (SoC) in locally advanced (LA) squamous cell carcinomas of the head and neck (SCCHN). While there is a well established dose effect relationship for RT alone in these cancers, it is not known whether this also applies to concomitant CT-RT. Methods: Patients were randomized between 75 Gy/7 weeks (Arm A) versus 70 Gy/35F in 7 weeks (Arm B). A sequential boost of 10 times 2.5 Gy after 50Gy/25F was given to the initial gross tumor volume (GTV) in Arm A. IMRT was used for arm A and 3D conformal RT for arm B. In both arms, patients (pts) received during RT 3 cycles of cisplatin at 100 mg/m2. Inclusion criteria were pts fit for receiving high dose cisplatin, non metastatic, non operated stage III-IV SCC of oral cavity, oro/hypopharynx. A 1:1 randomization was done by minimization on centers, N & T stages & GTV uni/bilateral. To detect a hazard ratio (HR) of 0.56 in locoregional (LR) control, inclusion of 310 pts was required to observe 109 LR progressions and achieve 85% power at 2-sided significance level of 0.05. Results: Between 2005 and 2015, 188 pts were randomized: 82% males, median age 58 years, 85% oropharynx. The accrual rate was slower than expected, due to the fact that IMRT became a SoC and was only allowed in arm A. As a consequence the trial was discontinued after inclusion of 188 patients. The majority of pts had stage IVa (73% vs 72%). All initial characteristics were well balanced between arms. The median follow-up was 4.7 years, not different between arms. Acute and late xerostomia were markedly improved in arm A (IMRT arm). The 1-year grade 0-1 salivary toxicity (RTOG) was 81% and 34% (p< 0.0001) in arm A and B respectively. At 3 years these rates were 92% vs 53% (p=0.0003). The increase of the dose to the GTV with IMRT did not transfer in a higher LR control probability with an adjusted HR of 0.88 [95%CI 0.51-1.52] (p=0.63). PFS, overall survival were not significantly different between the 2 arms. Conclusions: The dose escalation of RT to the GTV did not improve LR control in patients treated with concomitant CT-RT. This trial adds some new evidence level 1 in favor of IMRT in LA SCCHN. Clinical trial information: NCT00158678.