This study examines the effects of diversification strategy and board size on firm performance as well as the moderating effect of board size on the relationship between diversification strategy and ...firm performance in the Chinese tourism industry from 2008 to 2015. The results show that related diversification positively influenced Chinese tourism firm performance, and unrelated diversification negatively influenced it. Board size was found to negatively moderate the relationship between related diversification and firm performance and to positively moderate the relationship between unrelated diversification and firm performance. In addition, the results imply that small boards are beneficial to Chinese tourism firms when both related and unrelated diversification strategies are implemented.
BackgroundTCR-engineered T cell therapy has shown encouraging response rates in solid tumors, but complete responses are rare and partial responses are often short-lived. We submit that the primary ...reason underlying these results is that solid tumors exhibit heterogeneous target expression and HLA loss is common. Consequently, tumor cells that lack or lose the targeted antigen are resistant to single-targeted TCR-T therapies and drive relapse. To address these challenges, TScan has developed clinical trial assays to assess target expression and HLA loss in patient tumors. These assays enable prospective patient selection and assignment of treatment with multi-targeted TCR-T therapy. T-Plex is a multiplexed TCR-T cell product consisting of customized combinations of 2–3 TCR-T cell components selected from a pre-existing collection of TCR-Ts.MethodsTo enable T-Plex, TScan is developing an ImmunoBank of TCRs targeting MAGE-A1, HPV16, PRAME, and two additional undisclosed targets across multiple HLAs. TScan and Neogenomics have developed IHC and RNA-ISH assays to assess target expression in FFPE tumor samples. In addition, TScan and Tempus have developed a novel NGS-based pan-HLA-A/B/C Loss of Heterozygosity (LOH) algorithm to assess partial or clonal loss of HLA class I alleles in solid tumors.ResultsAnalysis of >150 tumor samples revealed the prevalence of MAGE-A1, HPV16, and PRAME across various solid tumor types. For example, PRAME expression was observed in 95% of melanoma samples, but only in 55% of NSCLC and HNSCC. Furthermore, the intensity and uniformity of expression varied considerably. H-scores for PRAME ranged from 66–300 (melanoma), 5–170 (NSCLC) and 2–135 (HNSCC). Similarly, MAGE-A1 expression was observed in 40% of melanomas and 20% of NSCLC and HNSCC. H-scores for MAGE-A1 varied considerably, ranging from 1–200 (melanoma), 1–50 (NSCLC) and 3–180 (HNSCC). Notably, co-expression of PRAME and MAGE-A1 was observed in ~31%, ~10% and ~9% of melanomas, NSCLC, and HNSCC, respectively. Heterogeneity of HLA expression was also observed. Data collected at Tempus showed that clonal and subclonal loss of HLA occurs in approximately 14% and 29% of melanomas, 23% and 16% of NSCLC, and 27% and 14% of HNSCC. Importantly, HLA-A/B/C alleles were almost always lost together, indicating that HLA loss most frequently occurs through haplotype loss, informing a strategy to direct multiplexed TCR-T to the remaining HLA haplotype.ConclusionsOverall, these data highlight the importance of a multiplexed TCR-T cell therapy targeting various intact tumor antigens presented on intact HLA alleles in order to effectively address solid tumors.Ethics ApprovalThe data presented in this abstract does not meet the definition of human subject research and animals were not used in this study.
Compared with photon-based techniques, proton beam radiation therapy (PBT) may improve the therapeutic ratio of radiation therapy (RT) for locally advanced pancreatic cancer (LAPC), but available ...data have been limited to single-institutional experiences. This study examined the toxicity, survival, and disease control rates among patients enrolled in a multi-institutional prospective registry study and treated with PBT for LAPC.
Between March 2013 and November 2019, 19 patients with inoperable disease across 7 institutions underwent PBT with definitive intent for LAPC. Patients received a median radiation dose/fractionation of 54 Gy/30 fractions (range, 50.4-60.0 Gy/19-33 fractions). Most received prior (68.4%) or concurrent (78.9%) chemotherapy. Patients were assessed prospectively for toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Kaplan-Meier analysis was used to analyze overall survival, locoregional recurrence-free survival, time to locoregional recurrence, distant metastasis-free survival, and time to new progression or metastasis for the adenocarcinoma cohort (17 patients).
No patients experienced grade ≥3 acute or chronic treatment-related adverse events. Grade 1 and 2 adverse events occurred in 78.7% and 21.3% of patients, respectively. Median overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and time to new progression or metastasis were 14.6, 11.0, 11.0, and 13.9 months, respectively. Freedom from locoregional recurrence at 2 years was 81.7%. All patients completed treatment with one requiring a RT break for stent placement.
Proton beam RT for LAPC offered excellent tolerability while still maintaining disease control and survival rates comparable with dose-escalated photon-based RT. These findings are consistent with the known physical and dosimetric advantages offered by proton therapy, but the conclusions are limited owing to the patient sample size. Further clinical studies incorporating dose-escalated PBT are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.
•Data comparing PROs with pencil beam and passive scattering are lacking.•We performed a comparison of EPIC domain scores for prostate cancer patients.•Results were sensitive to the methods used to ...compare PROs.•Future studies are needed to prospectively compare PROs following protons.
Although pencil beam scanning (PBS) is the most conformal method for proton beam therapy (PBT) delivery, it is unknown if outcomes differ compared to treatment with passive scatter/uniform scanning (PS/US). This analysis compares patient reported outcomes (PROs) following PBS and PS/US for prostate cancer (PC) in a prospective multicenter registry study.
We evaluated PROs with the Expanded Prostate Cancer Index Composite (EPIC) instrument for men with localized PC enrolled in PCG 001-09 (NCT01255748). PROs were assessed at baseline and through 12 months of follow-up. We compared mean changes in EPIC scores, as well as the proportions of men experiencing a one- and two-fold minimally important difference (MID) in domain scores, between PBS and PS/US. Multivariate analyses (MVAs) were performed to further evaluate the association between proton modality and PRO changes.
Three-hundred-and-four men completed EPIC at baseline; 72 received PBS and 232 received PS/US. The average quality-of-life (QOL) declines from baseline through 12 months did not significantly differ between the two groups. The proportion of men reporting a 1-MID decline at 12 months for PBS and PS/US was 34.3% and 27.4%, respectively, for urinary QOL (P = 0.27); 40. 1% and 40.9% for bowel QOL (P = 0.36); and 30. 1% and 36.6% for sexual QOL (P = 0.94). Corresponding 2-MID declines for PBS and PS/US were observed in 26.9% and 13.2% of men for urinary QOL (P = 0.01), 35.3% and 29.1% for bowel QOL (P = 0.33); and 16.4% and 18.1% for sexual QOL (P = 0.76). The association between proton modality and 2-MID changes in urinary QOL at 12-months remained significant on MVA (P = 0.007).
The results of this analysis show differences between PBS and PS/US with regards to two-fold MID changes in urinary function at 12 months, but no differences for average score declines over time. Future studies evaluating PRO measures between the two PBT modalities are warranted.
Travel photos can be symbols reflecting inner feelings of the photographers. They also serve as records that store travel experience of the photographers. By content analyzing 145 travel photos ...submitted to The New York Times, this paper aims to explore the relationships among motivations, image dimensions, and affective qualities of places. Findings indicate image dimension of natural resources such as “wealth of countryside”, “flora and fauna” and “beaches” are frequently associated with “arousing” and “pleasant” feelings toward a destination. On the other hand, image dimension of culture, history and art is frequently associated with “pleasant” quality of a place. These three association rules are in turn frequently linked to “intellectual” travel motivation. Photos that induce “arousing” and “pleasant” feelings are often taken in long shot, at eye-level angle, with stark density level and with single-person composition.
•Travel photos feature natural resources are frequently associated with arousing and pleasant feelings toward a destination.•Travel photos feature culture, history and art are frequently associated with pleasant quality of a place.•Photos inducing arousing and pleasant feelings are often taken in long shot and at eye-level angle.•Photos inducing arousing and pleasant feelings are often with stark density level and with single-person composition.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a distinct subtype of Hodgkin lymphoma, is a rare disease with a generally favorable prognosis. The hallmark of NLPHL is the presence of the ...lymphocytic and histiocytic cell, which, in contrast to the classic Reed-Sternberg cell, is CD20+, CD15−, and CD30−. NLPHL tends to have an indolent natural history, a long time to disease progression, a delayed time to relapse, and a high likelihood of presenting as early-stage disease. The evidence to guide the management of patients with NLPHL is limited by the rarity of this disease, but the available data support the use of involved-field radiation therapy alone for localized disease. Treatment-related late effects contribute significantly to the causes of death in patients treated for NLPHL.
PurposeReports of proton beam therapy (PBT) utilization for cutaneous melanoma of the head and neck (HN) region is virtually non-existent. This study reports on the efficacy and acute toxicities of ...PBT for primary HN cutaneous melanoma. Materials and MethodsWe queried the prospectively collected, multi-institutional Proton Collaborative Group registry for all consecutive patients with HN cutaneous melanoma receiving PBT from May 2010 to December 2019. Kaplan-Meier methods were used to estimate overall survival (OS), progression free survival (PFS), and local regional recurrence free survival (LRFS). Toxicity was reported per CTCAE version 4.0. ResultsA total of 8 patients were identified with a median age of 69 (range, 37-88). All patients (100%) underwent surgery followed with postoperative PBT. There were 3 patients (37.5%) with T3 or T4 disease and 4 (50%) with N2 or N3 disease. The median radiation dose was 46 GyRBE (range, 27-70) and median dose per fraction was 2.4 GyRBE (range, 2.0-6.0) with the most common dose fractionation being 44 or 48 GyRBE in 20 fractions (n = 4). At a median follow-up of 40.1 months (range, 1.6-62.4) the 1 and 3 year OS rates were 85.7% and 35.7%, respectively. The median PFS was 25.40 months (95% CI, 2.53-58.70) while PFS at 1 year and 3 years was 85.7% and 35.7%, respectively. LRFS was 100% at 1 year and 85.7% at 3 years. Five of the 8 patients developed distant metastases, of which 3 received immunotherapy. Acute G2+ and G3+ toxicities occurred in 5 of 8 patients and 2 of 8 patients, respectively. G3 toxicities included radiation dermatitis (n = 1) and immunotherapy-related rash (n = 1). No G4+ toxicities were reported. ConclusionSingle modality PBT for HN melanomas in the definitive setting provides effective and durable local control rates with tolerable acute toxicity. Distant failure remains the primary pattern of failure.
The present study assessed the effect of prostate gland size on patient-assessed quality of life (QOL) after definitive treatment of prostate adenocarcinoma with proton beam therapy. A larger ...prostate size, despite receiving a greater radiation dose, did not affect QOL at 6 months, providing further support that neoadjuvant cytoreductive treatments are unnecessary.
In the present study, we assessed the effect of prostate gland size on patient-assessed genitourinary and gastrointestinal (GI) quality of life (QOL) after definitive treatment of prostate adenocarcinoma with proton beam therapy.
As a part of a prospective outcome tracking protocol, 81 patients treated at a single center between with proton beam therapy completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before treatment and at the follow-up examinations. We reviewed the dosimetric data, reported as Vx (volume of organ receiving x Gy), and patient-reported QOL at 6 months. Genitourinary QOL was assessed using the American Urological Association symptom score and EPIC urinary domain score. GI QOL was assessed using the EPIC GI domain score.
Larger prostate glands were associated with greater bladder V70 (P < .01) and rectal V70 (P < .01). The rectal V70 was < 15% for all patients (range, 4%-13.8%) with the planned treatment volume coverage (percentage of the prescription dose covering 95% of the volume > 95%) maintained. Patients with larger prostates did not have a greater change in their American Urological Association symptom index scores (< 30 cm3, +2.3; 30-49 cm3, +3.2; ≥ 50 cm3, 0.2; P = .06) or urinary domain score (< 30 cm3, −3.6; 30-49 cm3, −3.1; ≥ 50 cm3, +3.8; P = .76) at 6 months after treatment. Also, prostate size was not associated with a change in the EPIC GI domain score at 6 months after treatment (< 30 cm3, −3.7; 30-49 cm3, −1.1; ≥ 50 cm3, −0.55; P = .67).
Definitive proton beam therapy for prostate cancer to a dose of 79.2 Gy resulted in excellent patient-reported urinary and GI QOL, independently of the baseline prostate size. This single-institution finding should be tested further in a multi-institutional study to confirm the potential limited role of androgen deprivation therapy.
For most disease sites, level 1 evidence is lacking for proton beam therapy (PBT). By identifying target populations that would benefit most from PBT, prospective registries could overcome many of ...the challenges in clinical trial enrollment. Herein, we report clinical outcomes of patients treated with PBT for locally advanced non-small cell lung cancer (LA-NSCLC).
Data were obtained from the multi-institutional prospective database of the Proton Collaborative Group (PCG). Inclusion criteria of our study were stage III de novo or recurrent LA-NSCLC, use of PBT, and availability of follow-up data. Overall survival (OS) time was calculated from the start of treatment until death or last follow-up. Kaplan-Meier curves were generated for groups of interest and compared with log-rank tests. Cox regression modeling was used to evaluate the multivariate association between selected covariates and OS.
A total of 195 patients were included in the analysis. PBT was given with a median equivalent dose in 2 Gy fractions (EQD2) of 63.8 Gy (relative biological effectiveness). Pencil beam scanning was used in 20% of treatments. Treatment-related grade 3 adverse events were rare: 1 pneumonitis, 2 dermatitis, and 3 esophagitis. No grade 4 events were reported. Two cardiac-related grade 5 events occurred in patients with multiple risk factors. The median follow-up time for living patients was 37.1 months and the median OS was 19.0 months. On multivariate analysis, good performance status (hazard ratio, 0.27; 95% confidence interval, 0.15-0.46; P < .0001), pencil beam scanning use (0.55; 0.31-0.97; P = .04), and increased EQD2 (0.80; 0.71-0.90 - per 10 Gy increase; P = .0002) were associated with decreased mortality.
PBT appears to yield low rates of adverse events with an OS similar to other retrospective studies on PBT for LA-NSCLC. PBS use and increased EQD2 can potentially improve OS.
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