PURPOSE:Radiation therapy (RT) is curative for the majority of patients with primary indolent orbital adnexal lymphoma (IOAL). Some reports suggest inferior outcomes for bilateral IOAL, leading to uncertainty regarding optimal management for this presentation. This multicenter, retrospective study evaluated long-term outcomes of bilateral IOAL patients treated with RT alone. METHODS AND MATERIALS:One hundred and eighty-four patients with synchronous (defined as ≤90 days between orbit diagnoses), or metachronous bilateral IOAL, and no prior lymphoma history, received RT to both orbits. Overall (OS), failure-free survival (FFS), freedom from local failure (FFLF), freedom from distant failure (FFDF), and toxicity were evaluated. The study met local institutional review board requirements. RESULTS:A total of 184 patients were treated for IOAL from 16 centers. The median age at first orbit diagnosis was 51 years (15-91 years) with 170 (92%) of patients having marginal zone lymphoma. Disease location included the conjunctiva in 265 (72%) of orbits. The RT dose (per orbit) was 4 Gy for 40 (11%), 20 to 26 Gy for 217 (59%), 27 to 30.6 Gy for 87 (24%), and >30.6 Gy for 24 (6.5%). Radiation therapy volume was whole orbit for 162 (44%), conjunctiva only for 177 (48%), and other partial orbit for 29 (8%). The median follow-up was 5.7 years. Ten-year OS and FFS were 99% (95% CI, 95-100) and 72% (95% CI, 62-79), respectively. Ten-year FFLF and FFDF were 87% (95% CI, 80-92) and 81% (95% CI, 72-88), respectively. Ten-year FFS was 85% (95% CI, 75-91) and 50% (95% CI, 32-65) for patients with conjunctival-only disease versus any nonconjunctival disease, respectively. Late toxicities included dry eye in 42% of patients (grade 1 in 86%) and cataract in 27%. CONCLUSIONS:In this large, multicenter experience, patients with bilateral IOAL treated with RT alone had outcomes comparable with historical series of unilateral disease. These results support the treatment of bilateral IOAL as a localized process with curative intent RT.

This large, single-institution series of patients with T3/T4 HPV+ OPSCC treated with either dCRT or upfront TORS +/- adjuvant therapy shows high FF-LRF and low rates of LRF leading to death regardless of treatment. Even in patients with advanced T stage, dCRT was able to obtain excellent disease outcomes. Future prospective studies are warranted to determine which combinations of multimodality therapy are optimal for LA HPV+ OPSCC, incorporating both oncologic and functional outcome endpoints.

Purpose A disparity exists in cancer screening rates for the Sexual and Gender Minority (SGM) community. We sought to understand the perceptions and baseline knowledge of cancer screening among SGM community members. Methods Survey administered via social media from June 2018 to October 2018. We asked 31 questions focused on cancer screening, human papillomavirus, emotional distress, and experience with the health care system. Those included were 18 years or older. Cancer screening attitudes and knowledge, as well as perceptions of the health care system were investigated. Results There were 422 respondents analyzed: 24.6% identified as female, 25.5% as male, 40.1% transgender, and 9.6% as other. 65.4% of the SGM community is not certain what cancer screening to do for themselves. Only 27.3% and 55.7% knew that HPV was a risk factor associated with head and neck cancer and anal cancer, respectively. Half stated their emotional distress prevents them from getting cancer screening. It was identified that process changes in making appointments, comforts during the visit, and formal training for physicians and nurses could increase cancer screening compliance for this community. The transgender population had a trend in more gaps in knowledge of appropriate cancer screening and significant excess emotional distress. Conclusion Gaps in cancer screening knowledge and emotional and financial distress may be responsible for the disparity of lower cancer screening rates for the SGM population and the transgender population may be most at risk. Appreciating the cancer screening concerns of the SGM population can help shape future clinical and institutional approaches to improve health care delivery.

Introduction Modern technologies, like intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), have improved the therapeutic ratio of thoracic radiotherapy (TRT) for lung cancer (LC). Halcyon™ (Varian Medical Systems, Palo Alto, CA, USA), a novel 6MV-flattening-filter-free O-ring linear accelerator (6X-FFF ORL), was designed to deliver IMRT and VMAT with greater speed than a C-arm linac. Herein, we report our initial clinical experience treating patients with LC on this linac. Methods All patients who received TRT for LC on the 6X-FFF ORL at our institution were retrospectively identified. Patients’ clinicopathologic data, radiotherapy details, early disease-control and toxicity outcomes, dosimetric data, couch corrections, and treatment times are reported. Results Between 10/2018-12/2019, 30 consecutive patients (median age 66 years, range 54-94 years) received definitive or post-operative TRT for LC (median 66 Gy/33 fractions; range 5-70 Gy/2-37 fractions) following four-dimensional computed tomography (CT) simulation (97%) using daily kilovoltage KV cone-beam CT (CBCT) (100%) on a 6X-FFF ORL for non-small cell LC (84%) or small cell LC (16%), with 53% receiving VMAT, 43% receiving static-field IMRT, and 77% receiving concurrent systemic therapy. All plans were approved through institutional peer review. The average three-dimensional vector couch correction based on CBCT guidance was 0.90 ± 0.50 cm. The average beam-on and beam on plus CBCT times were 1.7 ± 1.1 min, and 5.0 ± 3.2 min, respectively. Grade 3 dyspnea and fatigue occurred in 3% and 3% of patients, respectively. There were no grade ≥4 toxicities. Conclusion In this first clinical report of TRT for LC on a 6X-FFF ORL, daily CBCT-guided treatment was fast and safe with respect to dosimetry and clinical outcomes. Thus, use of this linac for TRT may increase LC patient throughput without a detriment in radiotherapy quality.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.

This article reviews the impact the obese state has on malignancy through inflammation and immune dysregulation using recent excerpts from the medical literature.The obese state creates a proinflammatory endocrinologic milieu altering cellular signaling between adipocytes, immunologic cells, and epithelial cells, leading to the over-activation of adipose tissue macrophages and the upregulation of compounds associated with carcinogenesis. Obesity correlates with a deficiency in numerous immunologic cells, including dendritic cells, natural killer cells, and T cells. In part, this can be attributed to a recent finding of leptin receptor expression on these immune cells and the upregulation of leptin signaling in the obese state. A number of clinical trials have demonstrated the feasibility of a high-fat, low-carbohydrate diet as an adjuvant treatment for cancer, and current trials are investigating the impact of this intervention on disease outcomes. In preclinical trials, a ketogenic diet has been shown to impede tumor growth in a variety of cancers through anti-angiogenic, anti-inflammatory, and proapoptotic mechanisms.Obesity is becoming more prevalent and its link to cancer is clearly established providing a rationale for the implementation of dietary interventions as an adjuvant therapeutic strategy for malignancy.

PURPOSE:Metastatic breast cancer is devastating and triple negative breast cancers (TNBC) have a higher propensity for metastasis. Improved local control upfront in this aggressive cancer could potentially decrease its propensity toward metastasis. We sought to determine if using caloric restriction (CR) as a systemic therapy, combined with radiation therapy (IR) to the primary tumor, may impact metastatic disease.METHODS:An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, IR, and a combination of the two. In vivo imaging was performed for metastatic evaluation. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for CR, which was then tested with pertinent pathway inhibition in the model.RESULTS:CR significantly increased the time to developing metastases, decreased the overall number and volume of lung metastases, and increased survival. CR decreased proliferation, increased apoptosis and globally downregulated the IGF-1R signaling pathway. Adding an IGF-1R/INSR inhibitor to local IR in vivo accomplished a decrease in metastases similar to CR plus IR, demonstrating the importance of the IGF-1R signaling pathway, and underscoring it as a possible mechanism for CR.CONCLUSIONS:CR decreased metastatic burden and therefore may complement cytotoxic therapies being used in the clinical setting for metastatic disease. Downregulation of the IGF-1R pathway, is in part responsible for this response and modulating IGF-1R directly resulted in similar improved progression-free survival. The novel use of CR has the potential to enhance clinical outcomes for patients with metastatic breast cancer.

PURPOSE OF REVIEW:This article reviews the impact the obese state has on malignancy through inflammation and immune dysregulation using recent excerpts from the medical literature.RECENT FINDINGS:The obese state creates a proinflammatory endocrinologic milieu altering cellular signaling between adipocytes, immunologic cells, and epithelial cells, leading to the over-activation of adipose tissue macrophages and the upregulation of compounds associated with carcinogenesis. Obesity correlates with a deficiency in numerous immunologic cells, including dendritic cells, natural killer cells, and T cells. In part, this can be attributed to a recent finding of leptin receptor expression on these immune cells and the upregulation of leptin signaling in the obese state. A number of clinical trials have demonstrated the feasibility of a high-fat, low-carbohydrate diet as an adjuvant treatment for cancer, and current trials are investigating the impact of this intervention on disease outcomes. In preclinical trials, a ketogenic diet has been shown to impede tumor growth in a variety of cancers through anti-angiogenic, anti-inflammatory, and proapoptotic mechanisms.SUMMARY:Obesity is becoming more prevalent and its link to cancer is clearly established providing a rationale for the implementation of dietary interventions as an adjuvant therapeutic strategy for malignancy.

MiR-21 is a well-characterized oncomir that is upregulated in multiple cancers, is associated with cancer prognosis, and has been linked to resistance to several chemotherapies. Its proven targets include tumor suppressor genes that govern basic principles of radiobiology including DNA repair, redistribution of cells in the cell cycle, and reoxygenation of hypoxic tumor areas. Therefore, we sought to investigate miR-21 to determine if it might serve as a novel approach to treat and sensitize cancers due to its dual role as an oncomir and radiation sensitizer. Normal human fibroblasts were exposed to radiation, H2O2, or etoposide. The effects of these stressors were determined by miRNA array analysis. Survival curves were performed in vitro with pre-miR-21 and anti-miR-21 transfection. Knock-out (KO) mice were designed and exposed to 6.5 Gy total body irradiation (TBI) and compared to control wild-type (WT) mice. Protein was made from various tissues from KO and WT mice (small intestine, brain, skin, lung and breast) and western blot analysis was performed for characterization. RT-PCR was also done to analyze miR-21 expression in WT and KO tissues. MicroRNA arrays found miR-21 to be significantly altered with all stressors but had a unidirectional response to etoposide, indicating double strand breaks may be responsible for the miR-21 radiation response. Survival curves demonstrated decreased survival in response to irradiation with anti-miR-21 transfection. miR-21 KO mice died at an average of 12 days after TBI and WT mice were still alive 9 months later. Western blot analysis revealed an increase in double strand breaks with γ-H2AX and increased apoptosis with increased caspase-3, and decreased bcl-2 in miR-21 KO compared with WT. RT-PCR revealed a temporary increase of miR-21 by 30% both in vitro and in vivo after exposure to radiation. A decrease in DNA repair genes such as MSH2 and STAG2 by at least 40% was noted depending on the tissue type assessed (lung, small intestine, skin, brain and fat pad/breast). Knock down of miR-21 in both the in vitro and in vivo settings reveals increased sensitivity to radiation with a noted increase in double strand breaks and apoptosis. Our data suggests miR-21 radiation sensitization may occur via a decreased ability for DNA repair. Since miR-21 is upregulated in many radioresistant tumors such as glioblastoma multiforme and resistant lung tumors, it may serve as a novel therapeutic target that warrants further evaluation.

OPINION article Front. Oncol., 04 June 2014Sec. Radiation Oncology Volume 4 - 2014 | https://doi.org/10.3389/fonc.2014.00133

An approach toward the carbon framework of various sesquiterpenes from the herbertane and cuparane families is described, including the concise total synthesis of enokipodin B. The key step is the construction of the vicinal quarternary centers of the skeleton through a tandem Nazarov cyclization/Wagner-Meerwein rearrangement mediated by a copper(II) complex. During this study, it was also found that changing the ligand architecture on the copper(II) promoter improved the chemoselectivity of the cationic rearrangement.