Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/µL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/µL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/µL, P=0.01) and larger target tumor volume (median 125 vs. 62 cm3, P=0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death (P=0.04); 1-year OS rates were 63% vs 77% (P=0.03). Receipt of photon versus proton-based RT (OR=3.50, P=0.02), higher mean liver dose (OR=1.19, P<0.01), and longer RT duration (OR=1.49, P=0.02) predicted severe lymphopenia. CONCLUSIONS: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Proton versus photon radiotherapy for hepatocellular carcinoma: Current data and technical considerations.

Radiation is an accepted standard of care for unresectable hepatocellular carcinoma (HCC), and while photon radiation is the current standard, the use of proton beam radiotherapy (PBT) is an active area of investigation given its ability to better spare uninvolved liver. Patients with HCC typically have background liver disease and many patients die of their underlying liver function in the absence of tumor progression. Early photon-based series showed promising rates of local control however the risk of non-classic radiation induced liver disease (RILD) remains relatively high and may be associated with poorer outcomes. There is a theoretical advantage to PBT in its ability to spare uninvolved liver parenchyma and potentially allow for further dose escalation. There are technical considerations for image guidance, respiratory motion management, and conformality to both PBT and photon radiotherapy that are critical to optimizing each modality. Whether the use of PBT affects clinical outcomes is the subject of the ongoing NRG Oncology GI003 trial, that randomizes patients with HCC to protons or photons. This article reviews the technical differences and literature on individual outcomes for PBT and photon radiation as well as the available comparative data.

Optimal Neoadjuvant Strategies for Locally Advanced Rectal Cancer by Risk Assessment and Tumor Location.

Neoadjuvant therapy is standard of care for locally advanced rectal cancer (LARC). Advancements in multimodality therapy options and sequencing of radiation therapy (RT), surgery, and chemotherapy make decision-making challenging. Traditional treatment of patients with LARC involves neoadjuvant chemoradiation followed by total mesorectal excision and consideration of adjuvant chemotherapy. Advancement in RT has led to trials offering both short-course and long-course RT with good long-term clinical outcomes. Intensification of therapy in high-risk patients has led to studies of total neoadjuvant therapy with chemotherapy and chemoradiation, now standard management for most LARC. De-escalation of therapy in patients with favorable prognosis has led to several considerations, including non-total mesorectal excision management or neoadjuvant chemotherapy only. Several considerations of patient and disease factors can help inform the optimal chemotherapy regimens in different sequencing of neoadjuvant strategies. Finally, novel biomarkers, such as microsatellite instability, has led to utilization of novel therapies, including neoadjuvant immunotherapy, with substantial response. This review attempts to frame the rapidly growing data in LARC in context of disease and patient risk factors, to inform optimal, personalized treatment of patients with LARC.

Leveraging Blood-Based Diagnostics to Predict Tumor Biology and Extend the Application and Personalization of Radiotherapy in Liver Cancers.

While the incidence of primary liver cancers has been increasing worldwide over the last few decades, the mortality has remained consistently high. Most patients present with underlying liver disease and have limited treatment options. In recent years, radiotherapy has emerged as a promising approach for some patients; however, the risk of radiation induced liver disease (RILD) remains a limiting factor for some patients. Thus, the discovery and validation of biomarkers to measure treatment response and toxicity is critical to make progress in personalizing radiotherapy for liver cancers. While tissue biomarkers are optimal, hepatocellular carcinoma (HCC) is typically diagnosed radiographically, making tumor tissue not readily available. Alternatively, blood-based diagnostics may be a more practical option as blood draws are minimally invasive, widely availability and may be performed serially during treatment. Possible blood-based diagnostics include indocyanine green test, plasma or serum levels of HGF or cytokines, circulating blood cells and genomic biomarkers. The albumin-bilirubin (ALBI) score incorporates albumin and bilirubin to subdivide patients with well-compensated underlying liver dysfunction (Child-Pugh score A) into two distinct groups. This review provides an overview of the current knowledge on circulating biomarkers and blood-based scores in patients with malignant liver disease undergoing radiotherapy and outlines potential future directions.

Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox.

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.

Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy.

BACKGROUND: Trimodality bladder-sparing therapy (TMT) is an acceptable treatment for selected patients with muscle-invasive urothelial cancer. Outcomes of TMT in histologic variants remains largely unknown. OBJECTIVE: To compare outcomes of pure urothelial carcinoma (PUC) to variant urothelial carcinoma (VUC) after TMT. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of patients treated with TMT at a single cancer center from 1993 until 2013. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier survival probabilities, and univariate and multivariable Cox regression analysis. RESULTS AND LIMITATIONS: Of 303 patients treated with TMT, 66 (22%) had VUC. Fifty (76%) had VUC with squamous and/or glandular differentiation and 16 (24%) had other forms. Complete response rate after induction TMT was 83% in PUC and 82% in VUC (p=0.9). The 5-yr and 10-yr disease-specific survival (DSS) was 75% and 67% in PUC versus 64% and 64% in VUC. The 5-yr and 10-yr overall survival (OS) was 61% and 42% in PUC versus 52% and 42% in VUC. On multivariable analysis VUC was not associated with DSS (hazard ratio: 1.3, 95% confidence interval: 0.8-2.2, p=0.3) or OS (hazard ratio: 1.2, 95% confidence interval: 0.8-1.7, p=0.4). Salvage cystectomy rates were similar (log-rank p=0.3). Limitations include retrospective design and restriction to variants of urothelial cancer. CONCLUSIONS: VUC responded to TMT, and there was no significant difference in complete response, OS, DSS, or salvage cystectomy rates compared with PUC. The presence of VUC should not exclude patients from TMT. PATIENT SUMMARY: The response of histologic variants of bladder cancer to bladder-sparing chemoradiation is largely unknown. We compared the outcomes of histologic variants of urothelial cancer to pure urothelial cancer in a large series of patients from a single institution. We found that variant histology does not significantly influence outcomes.

Painting Dose: The ART of Radiation.

The discovery of X rays in 1895 captivated society like no other scientific advance. Radiation instantly became the subject not only of numerous scientific papers but also of circus bazaars, poetry, fiction, costume design, comics, and marketing for household items. Its spread was "viral." What is not well known, however, is its incorporation into visual art, despite the long tradition of medicine and surgery as a subject in art. Using several contemporary search methods, we identified 5 examples of paintings or sculpture that thematically feature radiation therapy. All were by artists with exhibited careers in art: Georges Chicotot, Marcel Duchamp, David Alfaro Siqueiros, Robert Pope, and Cookie Kerxton. Each artist portrays radiation differently, ranging from traditional healer, to mysterious danger, to futuristic propaganda, to the emotional challenges of undergoing cancer therapy. This range captures the complex role of radiation as both a therapy and a hazard. Whereas some of these artists are now world famous, none of these artworks are as well known as their surgical counterparts. The penetration of radiation into popular culture was rapid and pervasive; yet, its role as a thematic subject in art never fully caught on, perhaps because of a lack of understanding of the technology, radiation's intangibility, or even a suppressive effect of society's ambivalent relationship with it. These 5 artists have established a rich foundation upon which pop culture and art can further develop with time to reflect the extraordinary progress of modern radiation therapy.

Education Research: Changing medical student perceptions of dementia: an arts-centered experience.

BACKGROUND: Medical students' comfort level working with dementia is poorly understood, and may impact subsequent experiences with patients and caregivers. Early experiences that take place in a nonmedical setting may allow students to gain a more comprehensive understanding of quality of life and disease management in everyday life. METHODS: We studied Columbia University preclinical medical students' perceptions of dementia relative to attending a nonclinical art-centered, museum-based experience designed for people with dementia and their caregivers. Participants individually attended a single 90-minute museum-based art-centered program designed to engage patients with dementia and caregivers; programs are attended by 6-10 patient-caregiver dyads and led by trained museum educators at existing New York City sites including The Metropolitan Museum of Art, The Cloisters, The Studio Museum in Harlem, and The New-York Historical Society. RESULTS: The Dementia Attitudes Scale (DAS) was administered before and after the intervention (least favorable = 20, neutral = 80, most favorable = 140). A total of 19 students completed baseline and postintervention DAS. At baseline, DAS mean = 97.4 (SD = 11.2). To limit bias of taking the test, 9 students completed a second preintervention DAS (≥1 week apart); among these, DAS increased from 95.7 (SD = 7.7) to 98.7 (SD = 7.4) (p = 0.09). Following the intervention, DAS favorably and significantly increased to 105.8 (SD = 11.0) (p ≤ 0.01 for all comparisons, paired-samples t test); greater differences were identified in comfort than knowledge of dementia. CONCLUSIONS: Although further study is warranted to confirm findings, given the increasing availability of such programs, it is reasonable to consider inclusion of these alongside other nonclinical programs that are already part of medical school curricula.