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We investigated whether adding radiation (RT) to systemic therapy improved outcomes in early stage diffuse large B-cell lymphoma (DLBCL) patients with or without double- or triple-hit lymphoma (DHL/THL) biology. This analysis included 183 patients profiled with fluorescent in situ hybridization (FISH) for alterations in MYC, BLC2, and/or BCL6. A total of 146 (80%) were non-DHL/THL, 27 (15%) were DHL, and 10 (6%) were THL. Systemic therapy without RT resulted in inferior freedom from relapse (FFR) (HR: 2.28; 95% CI, 1.10–4.77; p =.02). The median FFR for non-DHL/THL was not reached and was 33 and 22.3 months for DHL and THL, respectively; p <.001. Low-risk (R-IPI <2) DHL/THL patients treated with rituximab-based therapy had 3-year FFR rates of 11% and 71% for systemic therapy without and with RT, respectively; p =.04. No differences in overall survival were observed between the treatment groups. Treatment intensification with RT may improve early stage DHL/THL outcomes. [ABSTRACT FROM AUTHOR]

Background: Studies suggest treatment outcomes may vary between high (HVC)‐ and low‐volume centers (LVC). Radiation therapy (RT) for head and neck cancer (HNC) requires weeks of treatment, the inconvenience of which may influence a patient's choice for treatment location. We hypothesized that receipt of RT for HNC at a HVC would influence outcomes compared to patients evaluated at a HVC, but who chose to receive RT at a LVC. Methods: From 1998 to 2011, 1930 HNC patients were evaluated at a HVC and then treated with RT at either a HVC or LVC. Time‐to‐event outcomes and treatment factors were compared. Results: Median follow‐up was 34 months. RT was delivered at a HVC for 1368 (71%) patients and at a LVC in 562 (29%). Patients were more likely to choose HVC‐RT if they resided in the HVC's county or required definitive RT (all P < 0.001). HVC‐RT was associated with a significant improvement in 3‐year LRC (84% vs 68%), DFS (68% vs 48%), and OS (72% vs 57%) (all P < 0.001). On multivariate analysis (MVA), HVC‐RT independently predicted for improved LRC, DFS, and OS (all P < 0.05). Conclusions: In patients evaluated at a HVC, the choice of RT location was primarily influenced by their residing distance from the HVC. HVC‐RT was associated with improvements in LRC, DFS, and OS in HNC. As treatment planning and delivery are technically demanding in HNC, the choice to undergo treatment at a HVC may result in more optimal delivered dose, RT duration, and outcome. Patient choice to undergo radiation therapy at a high‐volume center (HVC) was primarily influenced by their residing distance from the HVC. HVC radiation treatment was associated with improvements in locoregional control, disease‐free survival, and overall survival in head and neck cancer. [ABSTRACT FROM AUTHOR]

Purpose Our goal was to determine whether tumour radiosensitivity is associated with activation of the immune system across all tumour types as measured by two gene expression signatures (GESs). Methods We identified 10,240 genomically profiled distinct solid primary tumours with gene expression analysis available from an institutional de-identified database. Two separate GESs were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity) and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumour samples and, in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterised, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumour radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation. Results Using an RSI cut-point of ≤0.3745, RSI-low tumours (n = 4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [−0.136, 1.095]) compared with RSI-high tumours (−0.17 [–0.82, 0.42]; p < 0.001) across all tumour samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early-stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p = 0.02), with RSI (hazard ratio [HR] 0.63 [95% confidence interval 0.36, 1.09]) and 12-CK (HR 0.66 [0.41, 1.04]) each providing comparable contributions. Conclusions Tumour radiosensitivity is associated with immune activation as measured by the two GESs. [ABSTRACT FROM AUTHOR]

Purpose Concurrent chemoradiotherapy (CRT) is the standard of care for many sites of locally advanced head and neck squamous cell carcinomas (LAHNC). However, on meta-analysis, the addition of chemotherapy did not improve survival for patients > 70 years. We hypothesized that elderly patients treated with CRT would have increased toxicity without similar improvements in survival. Methods A single-institution, IRB-approved retrospective study took place from 2005 to 2012 including 369 patients treated with CRT for LAHNC. Multivariate models for death at 3 months and death over time were developed using logistic regression and Cox modeling, respectively. Results Patients ≥ 70 years were treated less often with concurrent cisplatin dosed every 3 weeks (25.5% vs. 71.4%, respectively) and more often with weekly carboplatin (31.9% vs. 3.4%) than patients < 70 years ( n = 322; p < 0.001). Patients ≥ 70 years experienced increased toxicity during treatment with more frequently hospitalizations (36.2% vs. 21.1%; p = 0.02) and a lower rate of PEG removal at last follow-up or death (77.1% vs. 92.9%; p = 0.004). A higher proportion of patients ≥ 70 years died within 3 months (12.8% vs. 2.8%; p = 0.001) following CRT. Patients ≥ 70 had an increased risk of death at 3 months following CRT (odds ratio 5.19, 95% CI 1.64–16.41; p = 0.005) and worse survival over time (hazard ratio 2.30, 95% CI 1.34–3.93; p = 0.002). Conclusions Patients ≥ 70 years were more often treated with less toxic chemotherapy, yet experienced higher rates of hospitalization during treatment and increased rates of acute mortality following CRT. The efficacy of chemoradiotherapy for elderly patients should be evaluated in a prospective setting. [ABSTRACT FROM AUTHOR]

Background: Patients covered by Medicaid insurance appear to have poorer cancer outcomes. Herein, the authors sought to test whether Medicaid was associated with worse outcomes among patients with head and neck cancer (HNC).Methods: The records of 1698 patients with squamous cell HNC without distant metastatic disease were retrospectively reviewed from an institutional database between 1998 and 2011. At the time of diagnosis, insurance status was categorized as Medicaid, Medicare/other government insurance, or private insurance. Outcomes including locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan-Meier method and Cox regression multivariate analysis (MVA).Results: The median follow-up for all patients was 35 months. Medicaid patients comprised 11% of the population; the remaining patients were privately insured (56%) or had Medicare/government insurance (34%). On MVA, Medicaid patients were younger, were current smokers, had higher tumor T and N classifications, and experienced a longer time from diagnosis to treatment initiation (all P<.005). Medicaid insurance status was associated with a deficit of 13% in LRC (69% vs 82%) and 26% in OS (46% vs 72%) at 3 years (all with P<.001). A time from diagnosis to treatment initiation of >45 days was found to be associated with worse 3-year LRC (77% vs 83%; P = .009) and OS (68% vs 71%; P = .008). On MVA, Medicaid remained associated with a deficit in LRC (P = .002) and OS (P<.001).Conclusions: Patients with Medicaid insurance more often present with locally advanced HNC and experience a higher rate of treatment delays compared with non-Medicaid patients. Medicaid insurance status appears to be independently associated with deficits in LRC and OS. Improvements in the health care system, such as expediting treatment initiation, may improve the outcomes of patients with HNC. Cancer 2016;122:3529-3537. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the long-term outcome and patterns of failure in patients treated with primary radiotherapy (RT) for orbital lymphoma (OL). Seventy-nine patients diagnosed with stage IE OL between 1995 and 2012 were included. Fifty-nine patients (75%) had mucosa-associated lymphoid tissue lymphoma and 20 patients (25%) had follicular lymphoma subtype. The median follow-up was 49.7 months. Major tumor sites were conjunctiva (29%), orbit (47%) and lacrimal gland (24%). After treatment to a median dose of 30.6 Gy, there were a total of no local, one contralateral orbital, two regional and two distant recurrences, all outside of the treatment fields. The 10-year local relapse-free, distant metastasis-free and overall survival rates were 100%, 94.2% and 98.2%, respectively. Definitive RT to 30 Gy was shown to be highly effective for indolent OL, and this study represents one of the largest single-institution studies using primary RT for stage IE OL. [ABSTRACT FROM AUTHOR]

Cancer of the base of the tongue is a challenging disease for the head and neck surgeon, radiation oncologist and medical oncologist. However, over the last 10–15 years, improved treatment strategies have evolved which offer patients high probability of loco-regional control, survival, and good quality of life. The ability to offer patients good oncologic and functional outcomes serves as a paradigm for the successful application of multidisciplinary care, and the emphasis on quality of life in head and neck cancer treatment. This review provides an overview of the treatment options that exist, their advantages and disadvantages, and hopefully provides proper guidelines for the current management of this challenging disease. [Copyright &y& Elsevier]

Growing data supports the role of radiation therapy in the treatment of soft tissue sarcoma (STS). Brachytherapy has been used for decades in the management of STS and can be utilized as monotherapy or as a boost to external beam radiation. We present updated guidelines from the American Brachytherapy Society regarding the utilization of brachytherapy in the management of STS. Members of the American Brachytherapy Society with expertise in STS and STS brachytherapy created an updated clinical practice guideline including step-by-step details for performing STS brachytherapy based on a literature review and clinical experience. Brachytherapy monotherapy should be considered for lower-recurrence risk patients or after a local recurrence following previous external beam radiation; a brachytherapy boost can be considered in higher-risk patents meeting implant criteria. Multiple dose/fractionation regimens are available, with determination based on tumor location and treatment intent. Techniques to limit wound complications are based on the type of wound closure; wound complication can be mitigated with a delay in the start of brachytherapy with immediate wound closure or by utilizing a staged reconstruction technique, which allows an earlier treatment start with a delayed wound closure. These updated guidelines provide clinicians with data on indications for STS brachytherapy as well as guidelines on how to perform and deliver high quality STS brachytherapy safely with minimal toxicity. [ABSTRACT FROM AUTHOR]

Radiotherapy efficacy is the result of radiation-mediated cytotoxicity coupled with stimulation of antitumor immune responses. We develop an in silico 3-dimensional agent-based model of diverse tumor-immune ecosystems (TIES) represented as anti- or pro-tumor immune phenotypes. We validate the model in 10,469 patients across 31 tumor types by demonstrating that clinically detected tumors have pro-tumor TIES. We then quantify the likelihood radiation induces antitumor TIES shifts toward immune-mediated tumor elimination by developing the individual Radiation Immune Score (iRIS). We show iRIS distribution across 31 tumor types is consistent with the clinical effectiveness of radiotherapy, and in combination with a molecular radiosensitivity index (RSI) combines to predict pan-cancer radiocurability. We show that iRIS correlates with local control and survival in a separate cohort of 59 lung cancer patients treated with radiation. In combination, iRIS and RSI predict radiation-induced TIES shifts in individual patients and identify candidates for radiation de-escalation and treatment escalation. This is the first clinically and biologically validated computational model to simulate and predict pan-cancer response and outcomes via the perturbation of the TIES by radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose.Methods: We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical outcome in five clinical cohorts: Erasmus Breast Cancer Cohort (n=263); Karolinska Breast Cancer Cohort (n=77); Moffitt Lung Cancer Cohort (n=60); Moffitt Pancreas Cancer Cohort (n=40); and The Cancer Genome Atlas Glioblastoma Patient Cohort (n=98).Findings: We calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66-172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13-3·94, p=0·018).Interpretation: A GARD-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology.Funding: None. [ABSTRACT FROM AUTHOR]

Purpose Prior studies illustrated a reduction in wound complications with the use of staged reconstruction (SR) and negative pressure wound therapy when treating soft tissue sarcoma (STS) with surgical resection followed by high-dose-rate adjuvant brachytherapy. The purpose of this study is to compare the outcomes of SR and immediate reconstruction (IR) brachytherapy in recurrent STS. Methods and Materials A retrospective review of 40 patients with recurrent STS of the local extremity and trunk treated with resection followed by adjuvant brachytherapy alone. Margin status was defined as positive (SM(+)) if there was microscopic involvement (R1) or ≤1 mm margin and negative (SM(−)) if >1 mm margin was obtained. SR and IR were compared regarding toxicity, local control, and limb preservation. Results Median followup was 27 months. When comparing the SR ( n = 22) and IR ( n = 18) cohorts, there was a significantly lower final SM(+) rate in SR (32% vs. 83%, p < 0.01). A 2-year local control benefit seen with SR (80% vs. 34%; p = 0.012) and a final SM(−) (81% vs. 39%; p = 0.023). SR was associated with less toxicity on multivariate analysis, including a 90% decrease in persistent edema, an 80% decrease in wound dehiscence, and a 94% decrease in nonhealing wounds, when compared to IR. Ten of 31 (32%) extremity cases required eventual amputation from either chronic wound complications ( n = 4) or local recurrence ( n = 6). SR predicted for a benefit in 2-year limb preservation (88% vs. 50%; p = 0.008). Conclusion In our series, the treatment with SR brachytherapy resulted in less morbidity and an improved final SM(−) rate. This technique translated to an improvement in both local control and limb preservation of recurrent STS. [ABSTRACT FROM AUTHOR]