tbuckley/cabot-search huggingface dataset:
Long-term outcomes for re-irradiation of recurrent head-and-neck cancers: Report of acute and long-term toxicity.
Authors: Nima Aghdam, Ima Paydar, Aaron Bush, Ann Wild Gramza, Bruce J. Davidson, John F. Deeken, K. William Harter
Journal: Journal of Clinical Oncology (2018)

6077 Background: Long-term toxicity is a concern in patients undergoing head and neck re-irradiation. Durable local control is achieved in majority of patients in combination with chemotherapy and surgery. Here, we report the incidence and predictors of severe toxicity. Methods: From 2002 to 2016, 133 lesions in 123 patients received SBRT to the oropharynx (n = 21), hypopharynx (n = 8), nasopharynx (n = 9), paranasal sinus (n = 7), neck (n = 39), and other sites (n = 49). 92 lesions in 88 patients were treated definitively, and 41 lesions were treated with palliative intent. 36% underwent complete macroscopic resection before SBRT. Seventy-eight patients received chemosensitization. The median initial radiation dose was 70 Gy, and the median re-irradiation SBRT dose was 30 Gy (21-42.5 Gy) in 2-5 fractions. Median planning volume was 75 cm3 (6-645 cm3). Locoregional control (LRC) and overall survival (OS) were calculated using the Kaplan Meier method. χ2 test was utilized for differences in rates of acute and late toxicity. Severe toxicity was defined based on the RTOG Common Toxicity Criteria (≥grade 3). Logistic regression model was constructed to identify independent predictors of toxicity. Results: Median follow-up for surviving patients was 24.2 months. For definitively treated patients, 2-year OS and LRC rates were 42% and 36%, respectively. Durable local control was achieved in 56% of all patients. Of the patients treated definitively, 7.7% (n = 7) and 11% (n = 11) experienced severe acute and late toxicity, respectively. Patients who were treated in the neck and oropharynx experienced higher rates of severe late toxicity compared to other sites (19% vs 2%, p = 0.026). Additionally, there was a trend for higher acute severe toxicity in patients who received chemotherapy (11.4% vs. 0 %, p = 0.053). No patient experienced severe acute or late toxicity when re-treated with ≤ 30 Gy. Logistic regression model identified higher initial and re-irradiation dose as predictors of late severe toxicity. Conclusions: SBRT is an effective treatment for patients with locally recurrent or second malignancy in previously irradiated sites with acceptable toxicity.
Rare targetable drivers (RTD) in NSCLC: PD-L1 expression, tumor mutation burden (TMB), microsatellite instability (MSI) and outcomes with immune check-point inhibitors (ICPi).
Authors: Elizabeth Dudnik, Elias Bshara, Ahuva Grubstein, Ludmila Fridel, Tzippy Shochat, Laila C Roisman, Maya Ilouze, Anna B Rozenblum, Smadar Geva, Alona Zer, Ofer Rotem, Aaron Allen, Nir Peled
Journal: Journal of Clinical Oncology (2018)

9076 Background: The efficacy of ICPi in NSCLC with RTD is unknown. Methods: 82 consecutive patients (pts) with RTD (non-EGFR/ALK) were selected from the Davidoff Cancer Center database. The correlation between RTD type and TMB, MSI (by FoundationOne™ algorithm), and PD-L1 was analyzed. ORR, PFS with ICPi (RECIST 1.1) and OS were assessed; uni- and multivariate OS analysis was done. Results: Median age 63y (31-97); males 46%; smokers 50%; adenoca 87%. PD-L1, TMB, and MSI were assessed in 61%, 58%, and 57% pts, respectively (Table). Of 77 pts with advanced disease, 44 received ICPi. ORR with ICPi was 16%; median PFS was 3.2 mo (95% CI, 2.6-5). With median follow-up since ICPi initiation of 7.8 mo [IQR 4.2-14], 19/44 (43%) pts died, median OS was 16.2 mo (95% CI, 8.4-NR). No correlation was seen between OS with ICPi and PD-L1 (p-0.6), TMB (p-0.9), or RTD type (p-0.9). With median follow-up since advanced disease diagnosis (AdvDisDx) of 15 mo [IQR 7.2-24], 40/77 (52%) pts died, median OS was 32 mo (95% CI, 19.9-44.9) and 13 mo (95% CI, 6.6-15.9) for pts who were and were not exposed to ICPi, respectively (log rank test-6.3, p-0.01). In the multivariate analysis, ICPi exposure (p-0.04), targeted agents exposure (p < 0.01) and ECOG PS (p < 0.01) were the only variables which correlated with OS since AdvDisDx. Conclusions: Rare targetable drivers in NSCLC are associated with low/intermediate TMB, MSI stable status and variable levels of PD-L1 expression. ICPi outcomes are comparable to those of unselected NSCLC pts and largely unpredictable. ICPi exposure has independent impact on OS. Pts PD-L1, n/% TMB, n/% TMB, mut/Mb median, range MSI, n/% < 1% 1-49% ≥50% NA ≤5 6-19 ≥20 NA MS-S NA All 82 15/30 19/38 16/32 32 31/65 11/23 6/12 34 4, 0-57 47/100 35 BRAF V600E 9 2/25 4/50 2/25 1 4/57 1/14 2/29 2 4, 1-42 7/100 2 Non V600E 9 2/40 3/60 4 1/33 2/67 6 7, 2-14 3/100 6 HER2 13 1/11 8/89 4 8/89 1/11 4 2, 0-57 9/100 4 HER2 amp 6 2/67 1/33 3 1/33 2/67 3 38, 12-43 1/100 5 HER3 1 1 1/100 31 1/100 cMET ex14 14 2/22 1/11 6/67 5 5/83 1/17 8 4, 0-9 6/100 8 cMET amp 5 1/100 4 2/50 2/50 1 7, 0-10 4/100 1 RET 13 4/50 3/37 1/13 5 7/88 1/12 5 2, 0-7 8/100 5 RET 1 1/100 1 1 ROS1 9 1/20 2/40 2/40 4 4/57 3/43 2 5, 1-10 7/100 2 NTRAK 2 1/100 1 2 1/100 1
Genetic variants as predictive markers for ototoxicity and nephrotoxicity in patients (pts) with locally advanced head and neck cancer (LAHNC) treated with cisplatin-containing chemoradiotherapy (ccCRT).
Authors: Chantal Driessen, Janneke Ham, Dunja Maroeska W.M. Te Loo, Esther Van Meerten, Robert P. Takes, Winette T.A. Van Der Graaf, Johannes Kaanders, Marieke J.H. Coenen, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2018)

e18010 Background: Ototoxicity and nephrotoxicity are well-known, potentially irreversible, side effects of ccCRT in LAHNC pts. Several single-nucleotide polymorphism (SNP) as predictive markers of cisplatin toxicity were described before. The aim of this study is to investigate these SNPs as predictive markers for ototoxicity and nephrotoxicity in LAHNC pts treated with ccCRT. Methods: LAHNC pts treated with ccCRT at 2 university medical centers entered this prospective study and were genotyped for 10 SNPs in the genes ACYP2,COMT, TPMT,WFS1, OCT2, MATE1 and XPD and evaluated for their association with ototoxicity and nephrotoxicity. Ototoxicity was based on patients reports and scored based on CTCAE v 4.03, as well as on tone audiometrical assessments; nephrotoxicity was defined as a decline of ≥25% in creatinine clearance. Results: 102 pts entered the study and genetic data were available of 92 pts. Seven pts (8%) reported new hearing loss and based on tone audiometry 29% (27/85) had hearing loss of ≥25 dB. Nine pts were heterozygous for G/A for ACYP2 variant rs1872328; 6 of these pts (67%) reported hearing loss, leading to a significant association between carriership of the A allele in the ACYP2 gene and cisplatin-induced patient-reported ototoxicity, but not with ototoxicity measured by tone audiometry. Acute nephrotoxicity was found in 58% of the pts at any point during treatment and in 9% at end of treatment. Twenty-one pts were heterozygous for G/T or homozygous T/T for OCT2 variant rs316019, 16 of these pts (76%) had nephrotoxicity at any point during ccCRT. Carriership of a T allele in the OCT2 gene was significantly associated with acute nephroxotoxicity. No significant association was found for the other SNPs. Conclusions: We showed that in LAHNC pts, SNPs in OCT2 and ACYP2 are significantly related to nephrotoxicity and ototoxicity as determined by CTC v4.03, respectively. We did not find an association with hearing loss determined with tone audiometry; speech audiometry was not performed. Further research is needed before determination of SNPs can be used for individualized treatments plans.
A conversation approach based on shared goal-setting and shared decision-making for nurses in cancer aftercare: A developmental study.
Authors: Jolanda H Friesen, Gerrie JJW Bours, Ingrid CG Snijders, Trudy van der Weijden, Asiong GKS Jie, Anna JHM Beurskens
Journal: Journal of Clinical Oncology (2018)

e18878 Background: Although the relevance of goal-setting and shared decision-making in aftercare for cancer survivors is acknowledged, nurses do not always know how to implement them in practice. We aimed to develop and pretest a systematic conversation approach for nurses to tailor aftercare to oncology patient’s needs and goals. Methods: We used an user-centered iterative developmental process : 1. Identifying problems 2. Identifying overall objectives 3. Designing the intervention 4. Pretesting and adapting the intervention. Results: The main results of the problem identification were: non-systematic and incomplete screening of potential issues, caveats in providing information and involving patients in decision making. The overall objective formulated was: To develop a model for aftercare conversations based on shared goal-setting and shared decision-making. The conversation approach consists of four phases: 1. Preparation of the consultation including a questionnaire, 2. Shared goal-setting by means of a tool visualizing domains of life, and 3. Shared care planning by means of an overview of possible choices in aftercare, a database with health care professionals and a cancer survivorship care plan. 4. Evaluation. The results of the pretest revealed that the conversation approach needs to be flexible and tailored to the patient and practice setting, and embedded in the care processes. The conversation approach was perceived as enhancing patient-centeredness and leading to a more in-depth consultation. However, an important challenge for the nurses was to elicit patient preferences and set goals. Another challenge was the time-consuming nature of the approach. To facilitate the use of the conversation approach and the tools, we followed the suggestion to digitize parts of the conversation approach. Conclusions: Our model was co-created with important aftercare stakeholders, incorporates evidence-based cancer care guidelines and supports patient-centered care. The results of the pretest revealed important implications and suggestions for implementation, such as tailoring and embedding the approach within care processes.
Outcomes and costs of open, robotic, and laparoscopic radical hysterectomy for stage IB1 cervical cancer.
Authors: Daniel Jacob Margul, Junhua Yang, Brandon L. Seagle, Masha Kocherginsky, Shohreh Shahabi
Journal: Journal of Clinical Oncology (2018)

5502 Background: Surgery is the primary treatment modality for early cervical cancer. Compared to open (ORH), a robotic (RRH) or laparoscopic (LRH) approach to radical hysterectomy may have decreased morbidity, but the influence of surgical approach on survival, specific perioperative complications, and costs is unknown. Methods: The 2010-2013 National Cancer Database (NCDB) was used to evaluate the 5-year survival (5YS) of women with stage IB1 cervical squamous cell carcinoma or adenocarcinoma after radical hysterectomy performed open or by minimally invasive surgery (MIS). Survival times were estimated with the Kaplan-Meier method. Multivariable Cox proportional-hazards model (CPH) was used to adjust for measured confounders. The 2010-2015 Premier Healthcare Database was used to compare complications, length of stay (LOS), readmission rates, and hospitalization costs between ORH, RRH, and LRH. All p-values are two-sided. Results: From the NCDB, 982 and 910 women underwent ORH versus MIS radical hysterectomy, respectively. Women with a tumor size ≥ 2 cm who underwent MIS radical hysterectomy had decreased survival compared to women who underwent ORH (5YS (95% CI): 81.3% (75.6%-87.3%) versus 90.8% (87.7%-93.9%); hazard ratio (95% CI) 2.14 (1.36-3.38), P < 0.001). From Premier, 2830 women had radical hysterectomy: 45.1% (1277) ORH, 48.9% (1384) RRH, and 6% (169) LRH. ORH was associated with longer LOS compared to RRH or LRH (days, median (IQR): ORH 3 (3-5); RRH 1 (0-2); LRH 0 (0-2), P < 0.001). ORH also had a higher composite complication rate than RRH or LRH (ORH 44.9%; RRH 13.9%; LRH; 12.4%, P < 0.001), with increased bowel injuries, infections, electrolyte or fluid disorders, transfusions, and ileus (all P ≤ 0.001) associated with ORH. Thirty-day readmission rates were similar (ORH 2.3%; RRH 1.4%; LRH 1.8%, P = 0.17). Total surgical hospitalization costs favored MIS (P < 0.001 between groups) with median (IQR) values: ORH $12080 (8957-16052); RRH $11562 (8636-14600); LRH $9649 (7478- 13010). Conclusions: MIS is associated with decreased morbidity and costs. However, among women with ≥ 2 cm stage IB1 cervical cancer, MIS was associated with significantly decreased survival.
Differential effects of increasing time to treatment initiation (TTI) for solid tumors.
Authors: Thomas James Galloway, Lyudmila DeMora, Elizabeth A. Handorf, Richard J. Bleicher, Elin R. Sigurdson, Stacey Su, Sujana Movva, Eric M. Horwitz, Marc C. Smaldone, Angela Jain, Gina Mantia-Smaldone, Colin T Murphy, John A. Ridge
Journal: Journal of Clinical Oncology (2018)

e18520 Background: The comparative survival impact of increasing TTI for United States patients with different curable tumors is unknown. Methods: We queried the National Cancer Database for the TTI of patients treated with curative therapy for the following non-metastatic solid tumors (2003 – 2006): bladder, breast, cervix, colon, esophagus, gastric, head and neck (H&N), lung (NSCLC), pancreas, prostate, rectosigmoid, rectum, connective tissue, and uterus. Exclusion criteria included patients with unknown TTI, TTI > 365 days (d), distant metastases at diagnosis, in situ cancer, stage I bladder cancer, and palliative treatment. Overall survival (OS) was analyzed in each site using multivariable cox proportional hazards models. Adjustments were made for patient characteristics, stage of disease, and treatment modality. Additional site-specific variables were incorporated for some tumors (breast, cervix, pancreas, H&N) where appropriate. TTI was evaluated in discrete intervals with 0-7d evaluated as a separate interval to account for curative treatment started emergently. Results: 952,415 patients were included. Breast cancer was most common (n = 326,556, 34%). Esophagus (66%) and H&N (52%) cancer patients commonly began treatment with (chemo)radiation. All other sites most commonly began with an operation. Patients with prostate (44%), bladder (30%), cervix (21%), NSCLC (17%), and esophagus (16%) cancers commonly started treatment more than 60d after diagnosis. By contrast emergent treatment was most common (44%) in the lower GI tract (colon, rectosigmoid, rectum). This was associated with worse survival (HR 1.34, 95% CI 1.32 – 1.36) whether on day 0 or days 1-7. Bladder, breast, gastric, lower GI, H&N, and uterine cancers demonstrated worse OS for increasing TTI beyond 60 days on MVA, with the largest effect demonstrated for lower GI (HR 1.31, 95% CI 1.27-1.36) and uterine cancer (HR 1.23, 95% CI 1.16-1.30). Increasing TTI did not result in significantly worse outcomes for connective tissue, cervix, esophagus, NSCLC, pancreas, and prostate cancers. Conclusions: The impact of TTI on survival is not uniform. Some patients may benefit more than others from expeditious treatment initiation – most commonly from an operation.
Solid organ transplant after treatment for childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Andrew Charles Dietz, Kristy Seidel, Wendy M. Leisenring, Daniel A. Mulrooney, Jean M. Tersak, Richard D. Glick, Cathy A Burnweit, Daniel M. Green, Lisa Diller, Kevin C. Oeffinger, Susan A Smith, Rebecca M. Howell, Marilyn Stovall, Leslie L. Robison, Gregory T. Armstrong, Amanda M. Termuhlen
Journal: Journal of Clinical Oncology (2017)

10559 Background: Childhood cancer therapy is associated with late onset, organ-specific impairment. However, the prevalence of and outcomes after solid organ transplant (SOT) in childhood cancer survivors (CCS) are unknown. Methods: Data on U.S-based participants in the Childhood Cancer Survivor Study were linked with the Organ Procurement and Transplantation Network. Cumulative incidence of transplant (CIT) 35 years after cancer diagnosis, multivariable Cox regression models for hazard ratios (HR), Kaplan-Meier (KM) survival and corresponding 95% confidence intervals (CI) were estimated. Results: Among 13,318 survivors, median follow-up age 39 years (interquartile range, IQR 33-46), and median time since cancer diagnosis 31 years (IQR 28-36 years), 100 CCS had SOT after study entry with characteristics and outcomes provided (table). Conclusions: Organ-specific radiation and chemotherapy exposure increase the risk for SOT after childhood cancer. Five-year survival rates after renal and cardiac SOT are favorable. [Table: see text]
Inflammatory biomarkers as independent predictive and prognostic markers in metastatic colon cancer patients over several treatment lines.
Authors: Jakob M. Riedl, Florian Posch, Angelika Bezan, Florian Moik, Maria Anna Smolle, Joanna Szkandera, Martin Pichler, Herbert Stoger, Michael Stotz, Armin Gerger
Journal: Journal of Clinical Oncology (2017)

e15084 Background: The aim of this study is to quantify the value of the inflammatory biomarkers neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP) level and the advanced lung cancer inflammation index (ALI) as predictive and prognostic markers for treatment and survival outcomes over the first three chemotherapy lines in metastatic colorectal cancer (mCRC) patients. Methods: 258 patients with mCRC undergoing palliative chemo(immuno-)therapy were included in this retrospective study. Primary endpoints were 6-month progression free survival (PFS) and overall response rate (ORR) during 1st-line, 2nd-line, and 3rd-line treatment, and 6-month OS during best supportive care. Results: In multivariable analysis adjusting for polychemotherapy, 1 standard deviation (SD) increase in NLR was associated with a 8.5% absolute lower ORR in first line (95%CI: 11-7, p &lt; 0.0001), 3% lower ORR in second line (4-2, p &lt; 0.0001), and 3% lower ORR in third line (8-2, p = 0.24), respectively. The other inflammatory markers were not significantly associated with ORR. Regarding PFS, a higher NLR was consistently associated with higher risk of progression or death across all treatment lines, with rising hazard ratios (HR) over treatment lines (HR 1.30, p = 0.021 first line); (HR 1.37, p &lt; 0.0001 second line); (HR 1.44 , p = 0.042 third line). The PLR was associated with 6 month PFS over all lines. (HR 1.43 (95%CI 1.09 – 1.88, p = 0.009 first line); (HR1.67 (95%CI 1.34 – 2.09, p &lt; 0.0001 second line) and (HR 1.43 (95%CI 1.04 – 1.98, p = 0.029 in third line)) For CRP, the prognostic association was significant in the first two chemotherapy lines and in case of BSC. (HR 1.49 (95%CI 1.23 – 1.80, p &lt; 0.0001 first line); (HR1.25 (95%CI 1.06 – 1.47, p = 0.007 second line); (HR 1.09 (95%CI 0.81 – 1.48, p = 0.552 third line and HR 1.43 (1.15 – 1-79, p = 0.002 in BSC)). More detailed results concerning the other biomarkers will be presented at the meeting. Conclusions: Our data demonstrate that inflammatory biomarkers are important and independent indicators of response to antineoplastic chemotherapy, relevant not only in first, but also in later treatment lines.
Adapalene gel 0.1% vs. placebo as prophylaxis for anti-EGFR-induced acne-like rash: A randomized left-right comparative evaluation (APPEARANCE).
Authors: Motoko Tachihara, Naoko Chayahara, Yoshimi Fujishima, Atsushi Fukunaga, Ken Washio, Masatsugu Yamamoto, Kyosuke Nakata, Kazuyuki Kobayashi, Kei Takenaka, Masanori Toyoda, Naomi Kiyota, Kazutoshi Tobimatsu, Hisayo Doi, Naomi Mizuta, Naho Marugami, Atsushi Kawaguchi, Chikako Nishigori, Yoshihiro Nishimura, Toru Mukohara, Hironobu Minami
Journal: Journal of Clinical Oncology (2018)

10093 Background: Anti-EGFR drugs frequently cause acne-like rash. Adapalene (ADP), a topical retinoid used as first-line therapy for acne, is efficacious against acne-like rash induced by anti-EGFR drugs. To evaluate the prophylactic efficacy of ADP, we conducted a randomized, placebo (PLC)-controlled, evaluator-blinded, left-right comparative trial. Methods: Non-small cell lung, colorectal, or head and neck cancer patients scheduled to receive EGFR monoclonal antibodies (MABs) or tyrosine kinase inhibitors (TKIs) were randomly assigned to once daily ADP application on one side of the face, with PLC on the other side. All patients had topical moisturizer co-applied to both sides of the face, and received oral minocycline. The primary endpoint was the difference in total facial lesion count of acne-like rash at 4 weeks. A sample size of 26 has 80% power to detect a mean of paired differences of 15 with an estimated standard deviation of differences of 25 and a significance level of 0.05. Secondary endpoints included global skin assessment and ≥ grade 2 acne-like rash (MASCC scale) at 4 weeks. Two blinded dermatologists independently evaluated the endpoints from photographs. Results: From Feb 2016 to May 2017, 36 patients were enrolled, but 10 discontinued mainly because of poor adherence. Of the remaining 26 evaluable patients, 13 each received EGFR MABs or TKIs. Although the total lesion count did not differ with ADP treatment compared with PLC at baseline (0.6 vs 0.9), ADP treatment was unexpectedly associated with greater lesion count than PLC, although the difference was not statistically significant (12.6 vs 9.8, p = 0.1127). All 4 patients with a difference > 10 in lesion count between face sides had a greater lesion count on the ADP-treated side. No significant differences were observed in global skin assessment or incidence of ≥ grade 2 acne-like rash between ADP- and PLC-treated sides. The most common adverse event other than acne-like rash was dry skin, but the incidence did not differ between ADP- and PLC-treated sides (57% vs. 54%). Conclusions: Based on our findings, ADP is not recommended for the prevention of acne-like rash induced by anti-EGFR drugs. Clinical trial information: 000016692.