Andrzej Niemierko

Bio: Andrzej Niemierko is an academic researcher from Harvard University. The author has contributed to research in topics: Breast cancer & Radiation therapy. The author has an hindex of 57, co-authored 274 publications receiving 12764 citations. Previous affiliations of Andrzej Niemierko include Curie Institute & Cincinnati Children's Hospital Medical Center.

Relative biological effectiveness (RBE) values for proton beam therapy.

Abstract: Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs. As substantial clinical experience and additional experimental determinations of RBE have accumulated and the number of proton radiation therapy centers is projected to increase, it is appropriate to reassess the rationale for the continued use of a generic RBE and for that RBE to be 1.0–1.1. Methods and Materials: Results of experimental determinations of RBE of in vitro and in vivo systems are examined, and then several of the considerations critical to a decision to move from a generic to tissue-, dose/fraction-, and LET-specific RBE values are assessed. The impact of an error in the value assigned to RBE on normal tissue complication probability (NTCP) is discussed. The incidence of major morbidity in proton-treated patients at Massachusetts General Hospital (MGH) for malignant tumors of the skull base and of the prostate is reviewed. This is followed by an analysis of the magnitude of the experimental effort to exclude an error in RBE of ≥10% using in vivo systems. Results: The published RBE values, using colony formation as the measure of cell survival, from in vitro studies indicate a substantial spread between the diverse cell lines. The average value at mid SOBP (Spread Out Bragg Peak) over all dose levels is ≈1.2, ranging from 0.9 to 2.1. The average RBE value at mid SOBP in vivo is ≈1.1, ranging from 0.7 to 1.6. Overall, both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. There is agreement that there is a measurable increase in RBE over the terminal few millimeters of the SOBP, which results in an extension of the bioeffective range of the beam in the range of 1–2 mm. There is no published report to indicate that the RBE of 1.1 is low. However, a substantial proportion of patients treated at ≈2 cobalt Gray equivalent (CGE)/fraction 5 or more years ago were treated by a combination of both proton and photon beams. Were the RBE to be erroneously underestimated by ≈10%, the increase in complication frequency would be quite serious were the complication incidence for the reference treatment ≥3% and the slope of the dose response curves steep, e.g., a γ50 ≈ 4. To exclude ≥1.2 as the correct RBE for a specific condition or tissue at the 95% confidence limit would require relatively large and multiple assays. Conclusions: At present, there is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc. The experimental in vivo and clinical data indicate that continued employment of a generic RBE value and for that value to be 1.1 is reasonable. However, there is a local “hot region” over the terminal few millimeters of the SOBP and an extension of the biologically effective range. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in laboratory animal systems, especially as a function of dose/fraction in the range of 1–4 Gy.

Reporting and analyzing dose distributions: A concept of equivalent uniform dose

Abstract: Modern treatment planning systems for three-dimensional treatment planning provide three-dimensionally accurate dose distributions for each individual patient. These data open up new possibilities for more precise reporting and analysis of doses actually delivered to irradiated organs and volumes of interest. A new method of summarizing and reporting inhomogeneous dose distributions is reported here. The concept of equivalent uniform dose (EUD) assumes that any two dose distributions are equivalent if they cause the same radiobiological effect. In this paper the EUD concept for tumors is presented, for which the probability of local control is assumed to be determined by the expected number of surviving clonogens, according to Poisson statistics. The EUD can be calculated directly from the dose calculation points or, from the corresponding dose-volume distributions (histograms). The fraction of clonogens surviving a dose of 2 Gy (SF2) is chosen to be the primary operational parameter characterizing radiosensitivity of clonogens. The application of the EUD concept is demonstrated on a clinical dataset. The causes of flattening of the observed dose-response curves become apparent since the EUD concept reveals the finer structure of the analyzed group of patients in respect to the irradiated volumes and doses actually received. Extensions of the basic EUD concept to include nonuniform density of clonogens, dose per fraction effects, repopulation of clonogens, and inhomogeneity of patient population are discussed and compared with the basic formula.

Breast Cancer Subtype Approximated by Estrogen Receptor, Progesterone Receptor, and HER-2 Is Associated With Local and Distant Recurrence After Breast-Conserving Therapy

Abstract: Purpose To determine whether breast cancer subtype is associated with outcome after breast-conserving therapy (BCT) consisting of lumpectomy and radiation therapy. Patients and Methods We studied 793 consecutive patients with invasive breast cancer who received BCT from July 1998 to December 2001. Among them, 97% had pathologically negative margins of resection, and 90% received adjuvant systemic therapy. No patient received adjuvant trastuzumab. Receptor status was used to approximate subtype: estrogen receptor (ER) or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 negative = luminal A; ER+ or PR+ and HER-2+ = luminal B; ER–and PR –and HER-2+ = HER-2; and ER–and PR –and HER-2–= basal. Competing risks methodology was used to analyze time to local recurrence and distant metastases. Results Median follow-up was 70 months. The overall 5-year cumulative incidence of local recurrence was 1.8% (95% CI, 1.0 to 3.1); 0.8% (0.3, 2.2) for luminal A, 1.5% (0.2, 10) for luminal B, 8....

Age, Breast Cancer Subtype Approximation, and Local Recurrence After Breast-Conserving Therapy

Abstract: Purpose Prior results of breast-conserving therapy (BCT) have shown substantial rates of local recurrence (LR) in young patients with breast cancer (BC). Patients and Methods We studied 1,434 consecutive patients with invasive BC who received BCT from December 1997 to July 2006. Ninety-one percent received adjuvant systemic therapy; no patients received trastuzumab. Five BC subtypes were approximated: estrogen receptor (ER) or progesterone receptor (PR) positive, HER2 negative, and grades 1 to 2 (ie, luminal A); ER positive or PR positive, HER2 negative, and grade 3 (ie, luminal B); ER or PR positive, and HER2 positive (ie, luminal HER2); ER negative, PR negative, and HER2 positive (ie, HER2); and ER negative, PR negative, and HER2 negative (ie, triple negative). Actuarial rates of LR were calculated by using the Kaplan-Meier method. Results Median follow-up was 85 months. Overall 5-year cumulative incidence of LR was 2.1% (95% CI, 1.4% to 3.0%). The 5-year cumulative incidence of LR was 5.0% (95% CI, 3.0...

Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose

Abstract: Purpose : The equivalent uniform dose (EUD) for tumors is defined as the biologically equivalent dose that, if given uniformly, will lead to the same cell kill in the tumor volume as the actual nonuniform dose distribution. Recently, a new formulation of EUD was introduced that applies to normal tissues as well. EUD can be a useful end point in evaluating treatment plans with nonuniform dose distributions for three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. In this study, we introduce an objective function based on the EUD and investigate the feasibility and usefulness of using it for intensity-modulated radiotherapy optimization. Methods and Materials : We applied the EUD-based optimization to obtain intensity-modulated radiotherapy plans for prostate and head-and-neck cancer patients and compared them with the corresponding plans optimized with dose-volume-based criteria. Results : We found that, for the same or better target coverage, EUD-based optimization is capable of improving the sparing of critical structures beyond the specified requirements. We also found that, in the absence of constraints on the maximal target dose, the target dose distributions are more inhomogeneous, with significant hot spots within the target volume. This is an obvious consequence of unrestricted maximization target cell kill and, although this may be considered beneficial for some cases, it is generally not desirable. To minimize the magnitude of hot spots, we applied dose inhomogeneity constraints to the target by treating it as a “virtual” normal structure as well. This led to much-improved target dose homogeneity, with a small, but expected, degradation in normal structure sparing. We also found that, in principle, the dose-volume objective function may be able to arrive at similar optimum dose distributions by using multiple dose-volume constraints for each anatomic structure and with considerably greater trial-and-error to adjust a large number of objective function parameters. Conclusion : The general inference drawn from our investigation is that the EUD-based objective function has the advantages that it needs only a small number of parameters and allows exploration of a much larger universe of solutions, making it easier for the optimization system to balance competing requirements in search of a better solution.

Cancer treatment and survivorship statistics, 2016.

Abstract: The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.

sources and effects of ionizing radiation

Abstract: NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

Cancer treatment and survivorship statistics, 2012

Abstract: Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.

Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

Abstract: PurposeTo increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapyMethodsA multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline Guideline development involved a systematic review of the literature and an informal consensus process The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017ResultsThe systematic review identified 204 eligible publications Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports Due to the paucity of high-quality evidence on management