Risk Of Radiation-induced Cancer Research Articles

New method for generating breast models featuring glandular tissue spatial distribution

Abstract Mammography is the main radiographic technique used for breast imaging. A major concern with mammographic imaging is the risk of radiation-induced breast cancer due to the high sensitivity of breast tissue. The mean glandular dose (DG) is the dosimetric quantity widely accepted to characterize the risk of radiation induced cancer. Previous studies have concluded that DG depends not only on the breast glandular content but also on the spatial distribution of glandular tissue within the breast. In this work, a new method for generating computational breast models featuring skin composition and glandular tissue distribution from patients undergoing digital mammography is proposed. Such models allow a more accurate way of calculating individualized breast glandular doses taking into consideration the glandular tissue fraction. Sixteen breast models of four patients with different glandularity breasts were simulated and the results were compared with those obtained from recommended DG conversion factors. The results show that the internationally recommended conversion factors may be overestimating the mean glandular dose to less dense breasts and underestimating the mean glandular dose for denser breasts. The methodology described in this work constitutes a powerful tool for breast dosimetry, especially for risk studies.

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation.

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3-50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren's disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children.

Brachytherapy: state‐of‐the‐art radiotherapy in prostate cancer

Brachytherapy: state‐of‐the‐art radiotherapy in prostate cancer

Preliminary study of dose reduction and image quality of adult pelvic low-dose CT scan with adaptive statistical iterative reconstruction.

Because pelvic computed tomography (CT) is widely used in clinical practice, there are increasing concerns regarding the associated risks of radiation-induced cancer. Therefore, the capability to reduce the CT radiation dose without compromising image quality is desirable. To assess the radiation dose and image quality of adult pelvic CT using both a routine dose and low radiation dose with filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR). Forty-five patients underwent both routine-dose CT with FBP reconstruction and low-dose CT with FBP and 50% ASIR blending ratio (ASIR50) reconstruction, respectively. Three different groups of image data were compared for subjective and objective image quality. CT dose index volume (CTDIvol), dose-length product (DLP), and effective dose (ED) were recorded. The resulting CTDIvol, DLP, and ED following low-dose pelvic CT were 10.80 ± 6.0 mGy, 265.0 ± 55.0 mGy.Cm, and 3.97 ± 0.82 mSv, respectively. When compared with the values obtained following routine-dose pelvic CT, the low-dose pelvic CT values decreased by 62%, 55%, and 56%, respectively (P < 0.001). The results following evaluation of subjective and objective image quality revealed that there was no significant difference (P > 0.05) between routine-dose CT with FBP, and low-dose CT with ASIR50. However, significant differences were detected between low-dose CT with FBP, routine-dose CT with FBP, and low-dose CT with ASIR50 (P < 0.01). The application of low-dose pelvic CT with ASIR50 could dramatically reduce the radiation dose and substantially improve image quality.

Communicating Potential Radiation-Induced Cancer Risks From Medical Imaging Directly to Patients.

Over the past decade, efforts have increasingly been made to decrease radiation dose from medical imaging. However, there remain varied opinions about whether, for whom, by whom, and how these potential risks should be discussed with patients. We aimed to provide a review of the literature regarding awareness and communication of potential radiation-induced cancer risks from medical imaging procedures in hopes of providing guidance for communicating these potential risks with patients. We performed a systematic literature review on the topics of radiation dose and radiation-induced cancer risk awareness, informed consent regarding radiation dose, and communication of radiation-induced cancer risks with patients undergoing medical imaging. We included original research articles from North America and Europe published between 1995 and 2014. From more than 1200 identified references, a total of 22 original research articles met our inclusion criteria. Overall, we found that there is insufficient knowledge regarding radiation-induced cancer risks and the magnitude of radiation dose associated with CT examinations among patients and physicians. Moreover, there is minimal sharing of information before nonacute imaging studies between patients and physicians about potential long-term radiation risks. Despite growing concerns regarding medical radiation exposure, there is still limited awareness of radiation-induced cancer risks among patients and physicians. There is also no consensus regarding who should provide patients with relevant information, as well as in what specific situations and exactly what information should be communicated. Radiologists should prioritize development of consensus statements and novel educational initiatives with regard to radiation-induced cancer risk awareness and communication.

A method for calculating effective lifetime risk of radiation-induced cancer from screening mammography

PurposeTo propose a method for evaluating the effective lifetime risk of radiation-induced cancer from screening mammography and to present initial data for the UK National Breast Screening Programme. Material and methodsThe imaging was undertaken using a Hologic Selenia full field digital mammographic unit. The proposed method utilises an ATOM phantom containing thermoluminescent dosimeters and a perspex-polyethylene breast phantom to measure organ doses during a standard four view screening mammogram. Effective dose was calculated and effective risk was modelled for a range of client ages. The total lifetime effective risk was then calculated for the UK national screening programme. Calculation of effective risk includes the radiation dose to examined and contralateral breasts in addition to other body organs; this is an advantage over the mean glandular dose. ResultsThe contralateral breast, thyroid, thymus, brain, lung, salivary glands, and bone marrow all receive more than 1 μGy radiation dose during screening mammography. A major difference exists for total effective lifetime risk of radiation-induced cancer between clients with average and high breast cancer risk. Differences are attributed to the commencement age of screening and time interval between screens. ConclusionThis study proposes a method to evaluate effective lifetime risk of radiation-induced cancer from screening mammography in order to compare different mammography screening programmes.

Abstract 2246: Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells

Abstract Among the four main subtypes of breast cancer, basal-like breast cancer (the predominant subtype of triple-negative breast cancer) is of particular concern, due to its high frequency, relative lack of effective therapies and poor prognosis. Ionizing radiation (for example as treatment for other cancers) and cumulative exposure to steroid hormones (as seen in postmenopausal women under hormone replacement therapy) are known risk factors for breast cancer. Because of their tumor-initiating properties, cancer stem cells (CSCs) were proposed to be responsible for relapse and metastasis. In MCF10A non-cancerous basal-like PR-negative cells, progesterone treatment and 1 Gy X-rays generated ALDH+ and CD44+/CD24- CSCs. Here, we report that progesterone activated the Pi3k/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the Pi3k/Akt pathway counteracted the generation of CSCs by progesterone and irradiation. The stimulation of Pi3K/Akt by progesterone resulted in the inactivation of FOXO3 and a downregulation of miR-29 expression. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. This study provides a new mechanistic basis for progesterone and radiation-induced breast cancer risk. In addition, the elucidation of new pathways and miRNA regulations involved in CSC generation and maintenance may open the door to potential new strategies for basal cancer primary or adjuvant therapy, by blocking non-CSCs from replenishing the pool of CSCs and by targeting mechanisms responsible for CSC maintenance. Such CSC-focused therapies may be effective at preventing metastasis and relapse. Citation Format: Guillaume Vares, Sei Sai, Bing Wang, Akira Fujimori, Mitsuru Nenoi, Tetsuo Nakajima. Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2246. doi:10.1158/1538-7445.AM2015-2246

Risk of radiation-induced secondary rectal and bladder cancer following radiotherapy of prostate cancer

ABSTRACTBackground. An elevated risk of radiation-induced secondary cancer (SC) has been observed in prostate cancer patients after radiotherapy (RT), rising to as high as one in 70 patients with more than 10 years follow-up. In this study we have estimated SC risks following RT with both previous and contemporary techniques, including proton therapy, using risk models based on different dose-response relationships.Material and methods. RT plans treating the prostate and seminal vesicles with either conformal radiotherapy (CRT), volumetric modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) were created for 10 patients. The risks of radiation-induced cancer were estimated for the bladder and rectum using dose-response models reflecting varying degrees of cell sterilisation: a linear model, a linear-plateau model and a bell-shaped model also accounting for fractionated RT.Results. The choice of risk models was found to rank the plans quite differently, with the CRT plans having the lowest SC risk using the bell-shaped model, while resulting in the highest risk applying the linear model. Considering all dose-response scenarios, median relative risks of VMAT versus IMPT were 1.1–1.7 for the bladder and 0.9–1.8 for the rectum. Risks of radiation-induced bladder and rectal cancers were lower from VMAT if exposed at 80 years versus IMPT if exposed at 50 years.Conclusions. The SC risk estimations for the bladder and rectum revealed no clear relative relationship between the contemporary techniques and CRT, with divergent results depending on choice of model. However, the SC risks for these organs when using IMPT were lower or comparable to VMAT. SC risks could be assessed when considering referral of prostate cancer patients to proton therapy, taking also general patient characteristics, such as age, into account.

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts.

Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.

P0077 Risk assessment of radiation-induced secondary cancers when treating nasopharyngeal carcinoma with intensity modulated radiotherapy

Background This study investigated a method to evaluate the risk of radiation-induced secondary cancer based on whole-body dose measurements in patients with nasopharyngeal carcinoma (NPC) undergoing intensity modulated radiotherapy (IMRT). Methods We determined the relative position and contour of organs with the RANDO phantom to obtain accurate dose assessments for organs out-of-field of radiation. The treatment planning was simulated for RANDO phantom after the verifications of clinical doctors. Thermoluminescent dosimeters (TLDs) were placed in the phantom to estimate the actual organ doses delivered by IMRT. In this treatment planning for NPC with IMRT, the planning target volume (PTV) was 1066cm 3 and the prescribed dose required to deliver 6996 cGy in 33 fractions was 212 cGy for each irradiation. Findings The dose evaluation for the patients with NPC receiving IMRT showed that the highest equivalent dose received by their lungs was 4013.31±381.19mSv. According to the tissue weighting factors 60 and 103, recommended by the International Commission on Radiological Protection (ICRP), had whole-body effective doses of 998.11±0.46. 75mSv and 961.99±46.24mSv, respectively. The corresponding risks of radiation-induced secondary cancer obtained were 4.99% Sv −1 and 3.85% Sv −1 , respectively. Interpretation We showed that the risk assessments of radiation-induced secondary cancer of NPC with IMRT supported previous studies.

DEGRO practical guidelines for radiotherapy of non-malignant disorders: Part I: physical principles, radiobiological mechanisms, and radiogenic risk.

Synopsis of the introductory paragraph of the DEGRO consensus S2e-guideline recommendations for the radiotherapy of benign disorders, including physical principles, radiobiological mechanisms, and radiogenic risk. This work is based on the S2e-guideline recommendations published November 14, 2013. The basic principles of radiation physics and treatment delivery, evaluation of putative underlying radiobiological mechanisms, and the assessment of genetic and cancer risk following low-dose irradiation will be presented. Radiation therapy of benign diseases is performed according to similar physical principles as those governing treatment of malignant diseases in radiation oncology, using the same techniques and workflows. These methods comprise usage of orthovoltage X-ray units, gamma irradiation facilities, linear accelerators (LINACs), and brachytherapy. Experimental in vitro and in vivo models recently confirmed the clinically observed anti-inflammatory effect of low-dose X-irradiation, and implicated a multitude of radiobiological mechanisms. These include modulation of different immunological pathways, as well as the activities of endothelial cells, mono- and polymorphonuclear leukocytes, and macrophages. The use of effective dose for radiogenic risk assessment and the corresponding tumor incidence rate of 5.5%/Sv are currently controversially discussed. Some authors argue that the risk of radiation-induced cancers should be estimated on the basis of epidemiological data. However, such data are rarely available at present and associated with high variability. Current radiobiological studies clearly demonstrate a therapeutic effectiveness of radiation therapy used to treat benign diseases and implicate various molecular mechanisms. Radiogenic risks should be taken into account when applying radiation treatment for benign diseases.

Projected Effects of Radiation-Induced Cancers on Life Expectancy in Patients Undergoing CT Surveillance for Limited-Stage Hodgkin Lymphoma: A Markov Model.

Patients with limited-stage Hodgkin lymphoma (HL) undergo frequent posttreatment surveillance CT examinations, raising concerns about the cumulative magnitude of radiation exposure. The purpose of this study was to project radiation-induced cancer risks relative to competing risks of HL and account for the differential timing of each. We adapted a previously developed Markov model to project lifetime mortality risks and life expectancy losses due to HL versus radiation-induced cancers in HL patients undergoing surveillance CT. In the base case, we modeled 35-year-old men and women undergoing seven CT examinations of the chest, abdomen, and pelvis over 5 years. Radiation-induced cancer risks and deaths for 17 organ systems were modeled using an organ-specific approach, accounting for specific anatomy exposed at CT. Cohorts of 20-, 50-, and 65-year-old men and women were evaluated in secondary analyses. Markov chain Monte Carlo methods were used to estimate the uncertainty of radiation risk projections. For 35-year-old adults, we projected 3324/100,000 (men) and 3345/100,000 (women) deaths from recurrent lymphoma and 245/100,000 (men, 95% uncertainty interval [UI]: 121-369) and 317/100,000 (women, 95% UI: 202-432) radiation-induced cancer deaths. Discrepancies in life expectancy losses between HL (428 days in men, 482 days in women) and radiation-induced cancers (11.6 days in men, [95% UI: 5.7-17.5], 15.6 days in women [95% UI: 9.8-21.4]) were proportionately greater because of the delayed timing of radiation-induced cancers relative to recurrent HL. Deaths and life expectancy losses from radiation-induced cancers were highest in the youngest cohorts. Given the low rate of radiation-induced cancer deaths associated with CT surveillance, modest CT benefits would justify its use in patients with limited-stage HL.

Comparison of Three Dimensional Conformal Radiation Therapy, Intensity Modulated Radiation Therapy and Volumetric Modulated Arc Therapy for Low Radiation Exposure of Normal Tissue in Patients with Prostate Cancer

Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.

Avoiding Computed Tomography Scans By Using Point-Of-Care Ultrasound When Evaluating Suspected Pediatric Renal Colic

BackgroundAlthough renal colic in children in the United States remains relatively uncommon compared to in adults, its incidence has nearly doubled from 1999 to 2008. Noncontrast computed tomography (CT) is the current standard for the evaluation of suspected renal colic, given its high sensitivity and specificity. However, the greater lifetime risk of radiation-induced cancer from CT in pediatric patients has led to efforts to minimize radiation exposure. Additionally, pediatric renal colic is often recurrent, which might require multiple imaging studies during their lifetime. Point-of-care ultrasound (POCUS) by emergency physicians avoids radiation, has a low marginal cost, can be performed concurrently with other management, and allows for earlier diagnosis and more rapid treatment of renal colic. Adult randomized controlled trial evidence supports using POCUS as the initial approach to imaging and management of suspected renal colic. However, there remain limited data on POCUS in children for renal colic. Case ReportThis is a case series where the sonographic findings of hydronephrosis, ureteral jets, “twinkling artifact,” and the identification of urinary tract stones were used to evaluate adolescent and pediatric patients with renal colic. We report five cases of renal colic in adolescent and pediatric patients where urolithiasis was confirmed by using POCUS and irradiation by CT was avoided in all 5 patients. Why Should an Emergency Physician Be Aware of This?POCUS can provide information about the presence or absence of urinary tract stones as well as obstruction of the collecting system without the cost and radiation exposure of CT.

PO-0912: The risk of radiation-induced cancer following VMAT vs. IMPT of prostate cancer

PO-0912: The risk of radiation-induced cancer following VMAT vs. IMPT of prostate cancer

PO-1071 Radiation-induced cancer risk in breast cancer patients. Boost by photons or electrons? Definitive results

PO-1071 Radiation-induced cancer risk in breast cancer patients. Boost by photons or electrons? Definitive results

Calculation of Organs Doses and Secondary Cancer Risk during Mantle Field Radiotherapy for Hodgkin’s Lymphoma

Occurrence of radiation-induced secondary cancer risk following mantle field radiotherapy for Hodgkin's lymphoma (HL) patients with long survival demands well-established radiotherapy strategy. Organs doses and resulted secondary cancer risk due to out-of field photons were calculated during mantle field radiotherapy for Hl patient. The male and female mathematical phantom of the Oak Ridge National Laboratory (ORNL) and validated 6MV photon beam of a Varian 2300 C/D were modeled by MCNPX 2.4.0 MC code. Using suitable lungs and thyroid shields for AP and PA fields, the organ specific absorbed doses, effective dose, and secondary cancer risk were calculated following to mantle field radiotherapy for HL. Among the out-of-field organs, the nose, eyes, head and neck's skins and sinuses have the higher received doses. The total effective doses and secondary cancer risk for a male and female were estimated to be 199, 234 mSv and 1.72, 1.87 respectively. During mantle field radiotherapy for Hodgkin's lymphoma, accurately estimations of organs dose near to the field's edge and suitable shielding of critical in-field organs are crucial factor to establish an optimal treatment plan.

Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells

Ionizing radiation and cumulative exposure to steroid hormones are known risk factors for breast cancer. There is increasing evidence that breast tumors are driven by a subpopulation of tumor-initiating cancer stem cells (CSCs). In MCF10A non-cancerous basal-like PR− cells, progesterone treatment and X-rays generated ALDH+ and CD44+/CD24− CSCs. Here, we report that in irradiated MCF10A cells, progesterone activated the PI3K/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the PI3K/Akt pathway counteracted the generation of CSCs by progesterone and irradiation. The stimulation of PI3K/Akt via mPR resulted in the inactivation of FOXO transcriptional activity, the upregulation of snail and slug expression and a downregulation of miR-29 expression, which led to increased levels of KLF4, a transcription factor required for breast CSC maintenance. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. This study provides a new mechanistic basis for progesterone and radiation-induced breast cancer risk in basal cells. In addition, the elucidation of new pathways and miRNA regulations involved in CSC generation and maintenance may open the door to potential novel anti-CSC strategies.

On the estimation of radiation-induced cancer risks from very low doses of radiation and how to communicate these risks.

The article is intended to give a short overview of epidemiological data on cancer risks associated with very low absorbed doses of ionising radiation. The linear no-threshold (LNT) approach to estimate cancer risks involves the use of epidemiological data at higher doses (>100 mSv), but is supported by data from lower exposure of more sensitive population groups like fetuses and children and the presence of rare types of cancer. The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with a dose and dose-rate effectiveness (reduction) factor (DDREF) of 2 for extrapolation from high doses, should be used. The numerical value of the DDREF is challenged by the findings from some recent epidemiological studies demonstrating risks per unit dose compatible with the risks observed in the higher dose studies. In general there is very limited knowledge about the cancer risk after low absorbed doses (10-100 mSv), as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. Even if there may be significant deviations from linearity in the relevant dose range 0-100 mSv, one does not know the magnitude or even the direction of any such deviations. The risks could be lower than those predicted by a linear extrapolation, but they could also be higher. Until more results concerning the effects of low-dose exposure are available, a reasonable radiation protection approach is to consider the risk proportional to the dose.

A new approach to reduce uncertainties in space radiation cancer risk predictions.

The prediction of space radiation induced cancer risk carries large uncertainties with two of the largest uncertainties being radiation quality and dose-rate effects. In risk models the ratio of the quality factor (QF) to the dose and dose-rate reduction effectiveness factor (DDREF) parameter is used to scale organ doses for cosmic ray proton and high charge and energy (HZE) particles to a hazard rate for γ-rays derived from human epidemiology data. In previous work, particle track structure concepts were used to formulate a space radiation QF function that is dependent on particle charge number Z, and kinetic energy per atomic mass unit, E. QF uncertainties where represented by subjective probability distribution functions (PDF) for the three QF parameters that described its maximum value and shape parameters for Z and E dependences. Here I report on an analysis of a maximum QF parameter and its uncertainty using mouse tumor induction data. Because experimental data for risks at low doses of γ-rays are highly uncertain which impacts estimates of maximum values of relative biological effectiveness (RBEmax), I developed an alternate QF model, denoted QFγAcute where QFs are defined relative to higher acute γ-ray doses (0.5 to 3 Gy). The alternate model reduces the dependence of risk projections on the DDREF, however a DDREF is still needed for risk estimates for high-energy protons and other primary or secondary sparsely ionizing space radiation components. Risk projections (upper confidence levels (CL)) for space missions show a reduction of about 40% (CL∼50%) using the QFγAcute model compared the QFs based on RBEmax and about 25% (CL∼35%) compared to previous estimates. In addition, I discuss how a possible qualitative difference leading to increased tumor lethality for HZE particles compared to low LET radiation and background tumors remains a large uncertainty in risk estimates.