Purpose
To show that intrinsic radiosensitivity varies greatly for protons and carbon (C) ions in addition to photons, and that DNA repair capacity remains important in governing this variability.
...Methods
We measured or obtained from the literature clonogenic survival data for a number of human cancer cell lines exposed to photons, protons (9.9 keV/μm), and C‐ions (13.3–77.1 keV/μm). We characterized their intrinsic radiosensitivity by the dose for 10% or 50% survival (D10% or D50%), and quantified the variability at each radiation quality by the coefficient of variation (COV) in D10% and D50%. We also treated cells with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability.
Results
We found no statistically significant differences in the COVs of D10% or D50% between any of the radiation qualities investigated. The same was true regardless of whether the cells were treated with DNA repair inhibitors, or whether they were stratified into histologic subsets. Even within histologic subsets, we found remarkable differences in radiosensitivity for high LET C‐ions that were often greater than the variations in RBE, with brain cancer cells varying in D10% (D50%) up to 100% (131%) for 77.1 keV/μm C‐ions, and non‐small cell lung cancer and pancreatic cancer cell lines varying up to 55% (76%) and 51% (78%), respectively, for 60.5 keV/μm C‐ions. The cell lines with modulated DNA repair capacity had greater variability in intrinsic radiosensitivity across all radiation qualities.
Conclusions
Even for cell lines of the same histologic type, there are remarkable variations in intrinsic radiosensitivity, and these variations do not differ significantly between photon, proton or C‐ion radiation. The importance of DNA repair capacity in governing the variability in intrinsic radiosensitivity is not significantly diminished for higher LET radiation.
Breast-cancer-acquired lymphedema is routinely diagnosed from the appearance of irreversible swelling that occurs as a result of lymphatic dysfunction. Yet in head and neck cancer survivors, ...lymphatic dysfunction may not always result in clinically overt swelling, but instead contribute to debilitating functional outcomes. In this review, we describe how cancer metastasis, lymph node dissection, and radiation therapy alter lymphatic function, as visualized by near-infrared fluorescence lymphatic imaging. Using custom gallium arsenide (GaAs)-intensified systems capable of detecting trace amounts of indocyanine green administered repeatedly as lymphatic contrast for longitudinal clinical imaging, we show that lymphatic dysfunction occurs with cancer progression and treatment and is an early, sub-clinical indicator of cancer-acquired lymphedema. We show that early treatment of lymphedema can restore lymphatic function in breast cancer and head and neck cancer patients and survivors. The compilation of these studies provides insights to the critical role that the lymphatics and the immune system play in the etiology of lymphedema and associated co-morbidities.
Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed ...breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.
Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.
Of 170 breast cancer RCTs identified, 131 (77.1%) included PMBC patients. Sixty-five (38.2%) trials analyzed patients with hormone-receptor-positive (HR+) and HER2-negative (HER2-) breast cancer, of which 31 (47.7%) allowed for enrollment of PMBC patients. Lower rates of PMBC inclusion were seen in trials that studied HR+/HER2-patients (47.7% PMBC inclusion in HR+/HER2-trials vs. 94.3% in non-HR+/HER2-trials, aOR 0.07 95% CI: 0.02–0.19, p < 0.001) and in trials that randomized or mandated ET (44.4% in ET trials vs. 83.2% in non-ET trials, aOR 0.21 95% CI: 0.10–0.83, p = 0.02). Trials studying chemotherapy (CT) were associated with inclusion of PMBC patients (100% in CT trials vs. 70.5% in non-CT trials, a OR 14.02 95% CI: 1.54–127.91, p = 0.01). All surgical and radiation therapy clinical trials allowed for the inclusion of PMBC patients in their eligibility criteria.
Breast cancer clinical trials should carefully select their enrollment criteria and consider inclusion of premenopausal patients when appropriate.
•We investigated the inclusion of premenopausal breast cancer (PMBC) patients in clinical trials.•There was lower inclusion of PMBC in trials studying HR+/HER2-patients.•There was lower inclusion of PMBC in trials studying endocrine therapy.•Trials should carefully select their enrollment criteria and include PMBC patients when appropriate.
The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this ...technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group.
Patients were classified based on the CS groups of "suitable," "cautionary," and "unsuitable." Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease-free survival, cause-specific survival, and overall survival were assessed.
Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the "suitable" criteria, 430 patients (42%) who fit the "cautionary" criteria, and 176 patients (17%) who fit the "unsuitable" criteria. At a median follow-up of 53.5 months, the 5-year actuarial rates of IBTR for the "suitable," "cautionary," and "unsuitable" groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio OR, 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age <50 years and close-positive margins were associated with IBTR (OR, 1.12 P = .0079 and OR, 7.81 P = .0131, respectively).
The ASTRO CS groupings did not differentiate a subset of patients with a significantly worse rate of IBTR when they were treated with the MammoSite breast brachytherapy catheter to deliver APBI.
Background
Data are lacking about the benefit of adjuvant endocrine therapy (ET) in older patients with multiple comorbidities. The authors sought to determine the effect of ET on the survival of ...older patients who had multiple comorbidities and estrogen receptor (ER)‐positive/human epidermal growth factor receptor 2 (HER2)‐negative, pathologic node‐negative (pN0) breast cancer.
Methods
Women aged ≥70 years in the National Cancer Database (2010‐2014) with Charlson/Deyo comorbidity scores of 2 or 3 who had pathologic tumor (pT1)‐pT3/pN0, ER‐positive/HER2‐negative breast cancer were divided into 2 cohorts: adjuvant ET and no ET. Propensity scores were used to match patients based on age, comorbidity score, facility type, pT classification, chemotherapy, surgery, and radiation therapy. A Cox proportional hazards model was used to estimate the effect of ET on overall survival (OS).
Results
In the nonmatched cohort (n = 3716), 72.8% of patients received ET (n = 2705), and 27.2% did not (n = 1011). The patients who received ET were younger (mean age, 76 vs 79 years; P < .001) and had higher rates of breast conservation compared with those who did not receive ET (lumpectomy plus radiation: 43.4% vs 23.8%, respectively; P < .001). In the matched cohort (n = 1972), the median OS was higher in the ET group (79.2 vs 67.7 months; P < .0001). In the adjusted analysis, ET was associated with improved survival (hazard ratio, 0.70; 95% CI, 0.59‐0.83).
Conclusions
In older patients who have pN0, ER‐positive/HER2‐negative breast cancer with comorbidities, adjuvant ET was associated with improved OS, which may have been overestimated given the confounders inherent in observational studies. To optimize outcomes in these patients, current standard recommendations should be considered stage‐for‐stage based on life expectancy and the level of tolerance to treatment.
In older patients with multiple comorbidities and estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative, pathologic node‐negative breast cancer, adjuvant endocrine therapy is associated with improved survival. To optimize outcomes in these patients, current standard recommendations should be considered stage‐for‐stage based on life expectancy and level of tolerance to treatment.
Radiation Dose-Dependent Changes in Lymphatic Remodeling Kwon, Sunkuk; Janssen, Christopher F; Velasquez, Fred Christian ...
International journal of radiation oncology, biology, physics,
11/2019, Letnik:
105, Številka:
4
Journal Article
Recenzirano
Postoperative radiation therapy (RT) delivered to lymphatics is associated with an increased risk of developing lymphedema. Reported effects of RT on lymphatic vessels have varied, however, possibly ...because of the use of different animal models with varying surgery and radiation schedules and the inability to directly and longitudinally image lymphatics in vivo. Here we report, using noninvasive imaging, changes in lymphatic remodeling and function in response to surgery and RT in a mouse model.
Popliteal lymphadenectomy in mice preceded single-dose gamma irradiation of the lower extremity at a single dose of 0, 20, or 40 Gy. The right hind limb of intact mice was also radiated with 4 fractions (4 × 5 Gy). Near-infrared fluorescence lymphatic imaging with indocyanine green was performed over 6 months to monitor lymphatic vessel remodeling.
Postoperative mice treated with 20 Gy showed transient changes in lymphatic drainage, exacerbated vessel remodeling including qualitative vessel dilation and abnormal indocyanine green pooling from week 1 to 2, and initiation of restoration of lymphatic vessels, although dermal backflow was occasionally observed. Mice treated with 40 Gy showed steadily increasing lymphatic impairment until week 3 and extravasation of dye and dermal backflow in weeks 4 to 25. The ankles of mice treated with 40 Gy were significantly swollen from weeks 2 to 4 as compared with mice treated with 0 Gy or 20 Gy. Mice that received fractionated RT exhibited lymphatic vessel remodeling similar to remodeling that occurred when a single 20 Gy dose was given; however, dermal backflow did not resolve as it did in the case of a single 20 Gy dose.
The degree of nonreversing lymphatic damage seen in our mouse model was dependent on RT dose. Our results suggest that near-infrared fluorescence lymphatic imaging detection of early lymphatic changes can be used to predict development of lymphedema in patients with cancer.
Purpose
Breast cancer is the most common cancer in women globally and radiation therapy is a cornerstone of its treatment. However, there is an enormous shortage of radiotherapy staff, especially in ...low‐ and middle‐income countries. This shortage could be ameliorated through increased automation in the radiation treatment planning process, which may reduce the workload on radiotherapy staff and improve efficiency in preparing radiotherapy treatments for patients. To this end, we sought to create an automated treatment planning tool for postmastectomy radiotherapy (PMRT).
Methods
Algorithms to automate every step of PMRT planning were developed and integrated into a commercial treatment planning system. The only required inputs for automated PMRT planning are a planning computed tomography scan, a plan directive, and selection of the inferior border of the tangential fields. With no other human input, the planning tool automatically creates a treatment plan and presents it for review. The major automated steps are (a) segmentation of relevant structures (targets, normal tissues, and other planning structures), (b) setup of the beams (tangential fields matched with a supraclavicular field), and (c) optimization of the dose distribution by using a mix of high‐ and low‐energy photon beams and field‐in‐field modulation for the tangential fields. This automated PMRT planning tool was tested with ten computed tomography scans of patients with breast cancer who had received irradiation of the left chest wall. These plans were assessed quantitatively using their dose distributions and were reviewed by two physicians who rated them on a three‐tiered scale: use as is, minor changes, or major changes. The accuracy of the automated segmentation of the heart and ipsilateral lung was also assessed. Finally, a plan quality verification tool was tested to alert the user to any possible deviations in the quality of the automatically created treatment plans.
Results
The automatically created PMRT plans met the acceptable dose objectives, including target coverage, maximum plan dose, and dose to organs at risk, for all but one patient for whom the heart objectives were exceeded. Physicians accepted 50% of the treatment plans as is and required only minor changes for the remaining 50%, which included the one patient whose plan had a high heart dose. Furthermore, the automatically segmented contours of the heart and ipsilateral lung agreed well with manually edited contours. Finally, the automated plan quality verification tool detected 92% of the changes requested by physicians in this review.
Conclusions
We developed a new tool for automatically planning PMRT for breast cancer, including irradiation of the chest wall and ipsilateral lymph nodes (supraclavicular and level III axillary). In this initial testing, we found that the plans created by this tool are clinically viable, and the tool can alert the user to possible deviations in plan quality. The next step is to subject this tool to prospective testing, in which automatically planned treatments will be compared with manually planned treatments.
Breast cancer-related lymphedema (BCRL) occurs in ~ 40% of patients after axillary lymph node dissection (ALND), radiation therapy (RT), or chemotherapy. First-line palliative treatment utilizes ...compression garments and specialized massage. Reparative microsurgeries have emerged as a second-line treatment, yet both compression and surgical therapy are most effective at early stages of LE development. Identifying patients at the highest risk for BCRL would allow earlier, more effective treatment. Perometric arm volume measurements, near-infrared fluorescent lymphatic imaging (NIRF-LI) data, and blood were collected between 2016 and 2021 for 40 study subjects undergoing treatment for breast cancer. Plasma samples were evaluated using MILLIPLEX human cytokine/chemokine panels at pre-ALND and at 12 months post-RT. A Mann-Whitney
-test showed that G-CSF, GM-CSF, IFN-2α, IL-10, IL-12p40, IL-15, IL-17A, IL-1β, IL-2, IL-3, IL-6, and MIP-1β were significantly higher at pre-ALND in those presenting with BCRL at 12 months post-RT. MIP-1β and IL-6 were significantly higher at pre-ALND in those who developed dermal backflow, but no BCRL, at 12 months post-RT. Plasma IL-15, IL-3, and MIP-1β were elevated at 12 months after RT in those with clinical BCRL. These findings establish BCRL as a perpetual inflammatory disorder, and suggest the use of plasma cytokine/chemokine levels to predict those at highest risk.
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