A Qualitative Analysis of Medical Student Reflections Following Participation in a Canadian Radiation Oncology Studentship.

Exposure to radiation oncology in medical school curricula is limited; thus, mentorship and research opportunities like the Dr. Pamela Catton Summer Studentship Program attempt to bridge this gap and stimulate interest in the specialty. In 2021, the studentship was redesigned as virtual research, mentorship, and case-based discussions due to the COVID-19 pandemic. This study explores the impact of COVID-19 on the studentship, on students' perceptions of the program, and on medical training and career choice. Fifteen studentship completion essays during 2021-2022 were obtained and anonymized. Thematic analysis was performed to interpret the essays with NVivo. Two independent reviewers coded the essays. Themes were established by identifying connections between coded excerpts. Consensus was achieved through multiple rounds of discussion and iteratively reviewing each theme. Representative quotes were used to illustrate the themes. The themes confirmed the studentship was feasible during the pandemic. Perceived benefits of the program included mentorship and networking opportunities; gaining practical and fundamental knowledge in radiation oncology; developing clinical and research skills; and creating positive attitudes towards radiation oncology and the humanistic aspect of the field. The studentship supported medical specialty selection by helping define student values, shaping perceptions of the specialty, and promoting self-reflection upon students' personal needs. This study informs future iterations of the studentship to promote radiation oncology in Canadian medical school curricula. It serves as a model for studentships in other specialties that have limited exposure and similar challenges with medical student recruitment.

Safety of CDK4/6 Inhibitors Combined with Radiotherapy in Patients with Metastatic Breast Cancer: A Review of the Literature.

Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the effect and toxicities of RT. A comprehensive review of the literature on the combination of RT and CDK4/6 inhibitors was performed with 19 eligible studies included in the final analysis. A total of 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies, 4 case reports, 3 case series, and 3 letters to the editor. The CDK4/6 inhibitor used, RT target, and RT technique were assessed in terms of toxicities. This literature review demonstrates generally limited toxicities with the combination of CDK4/6 inhibitors and palliative radiotherapy to metastatic breast cancer patients. The current evidence is nonetheless limited, and further results of ongoing prospective clinical trials will help clarify whether these treatments can be safely combined.

Case report: Ultrahypofractionated palliative breast radiotherapy for a fungating invasive mammary carcinoma.

Palliative radiotherapy for symptomatic and intact breast tumors must balance convenience, efficacy, and risk of acute toxicity. This case report presents a patient with metastatic breast cancer and an intact fungating primary tumor. She was treated with an ultrahypofractionated radiation therapy, 26 Gy in 5 consecutive daily fractions, with sequential palliative chemotherapy. This resulted in a minimal toxicity profile and significant reduction of tumor burden and symptoms.

Locoregional Management of Breast Cancer: A Chronological Review.

Locoregional management of breast cancer is founded on evidence generated over a vast time period, much longer than the career span of many practicing physicians. Oncologists rely on specific patient and tumour characteristics to recommend modern-day treatments. However, some of this information may not have been available during prior periods in which the evidence was generated. For example, the comprehensive Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analyses published in the 2000s typically included older trials accruing patients between the 1960s and 1980s. This raises some uncertainty about whether conclusions from studies conducted in prior eras are as relevant or applicable to modern-day patients and treatments. Reviewing the chronological order and details of the evidence can be beneficial to understanding these nuances. This review discusses the evolution of locoregional management through some key clinical trials. We aim to highlight the time period in which the evidence was generated and emphasize the 10-year outcomes for the comparability of results. Evidence supporting surgical management of the breast and axilla, as well as details of radiotherapy are discussed briefly for all stages of breast cancer.

Radiation Therapy With Cyclin-Dependent Kinase 4/6 Inhibitors: A Multi-institutional Safety and Toxicity Study.

PURPOSE: Our purpose was to investigate radiation therapy (RT) toxicity when given with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) compared with RT alone. METHODS AND MATERIALS: We conducted a retrospective cohort study of patients with hormonal receptor-positive and human epidermal growth factor-2 negative metastatic breast cancer treated with RT at 4 cancer centers in Alberta, Canada, between 2016 and 2020. Toxicity in patients treated with RT within 30 days of initiating to discontinuing CDK4/6i (RT + CDK4/6i) was compared with toxicity of RT in CDK4/6i-naïve patients (RT alone). The primary outcome was acute grade (G) 2 or higher, nonhematological toxicity within 30 days of RT. We also explored toxicity based on the timing of RT (prior, concurrent, post) in relation to CDK4/6i. Propensity score matching was applied to create comparable cohorts. A generalized linear mixed model was used to evaluate factors associated with acute toxicity. RESULTS: One hundred thirty-two patients (220 RT sites) in the RT + CDK4/6i and 53 patients (93 RT sites) in RT alone were eligible. The rate of acute G2 or higher nonhematological toxicity was 11.5% versus 7%, respectively (P = .439), and acute G3 or higher nonhematological toxicity was 3.7% versus 0%, respectively (P = .151). Acute toxicity in RT + CDK4/6i group was mainly observed when RT was given concurrently (67%), with most of the G3 toxicity recorded. After propensity score matching, the association of acute toxicity with RT + CDK4/6i versus RT alone was not significant on multivariable analysis (odds ratio, 3.13; 95% confidence interval, 0.74-13.2; P = .121). CONCLUSIONS: We did not observe a significant association between CDK4/6i use and acute G2 or higher nonhematological toxicity in women with metastatic breast cancer receiving palliative RT. Given the findings of G3 toxicity, caution is advised whenever CDK4/6i is given concurrently with RT.

Mapping the Current State of Canadian Medical School Oncology Interest Groups.

Cancer is the leading cause of mortality in Canada. Undergraduate medical education therefore must ensure adequate oncology education for all physicians and inspire some to make oncology their career specialty, in an effort to ensure public care needs are met in the future. Medical student-led oncology interest groups (OIGs) are a subset of specialty interest groups that supplement formal didactic and clinical learning to increase exposure to oncology and access to mentors. We conducted a survey of OIG leaders to ascertain their goals, activities, barriers, future directions, and perceptions about employment prospects. OIG leaders from 12/17 Canadian medical schools responded. Medical oncology was the most represented specialty in OIGs. Half of OIGs had faculty mentors. Self-reported goals were to increase exposure to oncology disciplines (n = 12), assist students with career selection (n = 11) and finding mentors (n = 7), and enhance oncology education (n = 10). OIGs held on average 5 events per year (range 1-12). Reported barriers were finding time to plan events, declining student interest over academic year, and limited funding. Many OIGs showed interest in more standardized resources about oncology disciplines (n = 9), access to presentations (n = 10), more funding (n = 7), and collaboration (n = 7). Employment in many oncology specialties was perceived poorly, and the most important career selection considerations were ease of employment, practice location, and partner/family preference. Our survey highlights common goals, barriers, and perceptions in OIG medical student leaders across Canada and provides guidance for future interventions.

Acute Care Use by Breast Cancer Patients on Adjuvant Chemotherapy in Alberta: Demonstrating the Importance of Measurement to Improving Quality.

Breast cancer patients receiving adjuvant chemotherapy are at increased risk of acute care use. The incidence of emergency department (ED) visits and hospitalizations (H) have been characterized in other provinces but never in Alberta. We conducted a retrospective population-based cohort study using administrative data of women with stage I-III breast cancer receiving adjuvant chemotherapy. Rates of ED and H use in the 180 days following chemotherapy initiation were determined, and logistic regression was performed to identify risk factors. We found that 47% of women receiving adjuvant chemotherapy experienced ED or H, which compared favourably to other provinces. However, Alberta had the highest rate of febrile neutropenia-related ED visits, and among the highest chemotherapy-related ED visits. The incidence of acute care use increased over time, and there were significant institutional differences despite operating under a single provincial healthcare system. Our study demonstrates the need for systematic measurement and the importance of quality improvement programs to address this gap.

Higher-risk breast cancer in women aged 80 and older: Exploring the effect of treatment on survival.

BACKGROUND: To understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors. MATERIALS AND METHODS: We conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS). RESULTS: 1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes. CONCLUSIONS: Surgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients.

DUCHESS: an evaluation of the ductal carcinoma in situ score for decisions on radiotherapy in patients with low/intermediate-risk DCIS.

BACKGROUND: Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score®) and clinicopathological features (CPFs), on its ability to change radiation oncologists' recommendations for RT after BCS for DCIS. METHODS: Prospective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45 years, tumor ≤ 2.5 cm, and margins ≥ 1 mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation. RESULTS: 217 patients were evaluable, with mean age = 63 years, mean tumor size = 1.1 cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39-54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1-41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22-35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict. CONCLUSION: The DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.

Neuropsychological impact of white matter hyperintensities in older adults without dementia.

The purpose of this study was to determine (a) if simple clinical judgements of white matter hyperintensities (WMH) on imaging are associated with measurable cognitive impacts in otherwise cognitively normal older adults, (b) if neuropsychological measures can predict those with WMH, and (c) the frequency of low cognitive scores in those with WMH on a battery of measures. Forty-four individuals judged free of other cognitive disorders despite moderate to extensive WMH were compared with 50 individuals matched on age (mean of 83), education (college educated), and gender (predominantly female). Data was obtained from the National Alzheimer's Coordinating Center database. The group with at least moderate WMH had lower scores on the Trail Making Test A, verbal fluency, and digit span. A component score derived from these measures was a significant predictor of the presence of WMH, though only correctly classified 68% of participants. Even in individuals free from other suspected conditions, clinically judged moderate to extensive WMH was associated with cognitive weaknesses for processing speed, working memory, and executive functioning. This shows that a relatively simple judgment of WMH burden is meaningfully associated with worse cognition. Implications and future directions for are discussed.

A retrospective analysis to demonstrate achievable dosimetry for the left anterior descending artery in left-sided breast cancer patients treated with radiotherapy.

PURPOSE: To demonstrate achievable dose for the left anterior descending artery (LAD) for left-sided breast cancer patients. METHODS: A retrospective analysis was conducted on all left-sided breast cancer patients receiving whole breast or post-mastectomy chest wall irradiation between 2013 and 2018. All patients in this study were treated with tangent-based techniques with the LAD prospectively contoured as routine clinical care. This large patient cohort was used to benchmark achievable mean doses to the LAD in the context of heart dose. The primary cohort of study were patients undergoing treatment with deep-inspiration breath-hold (DIBH), stratified by internal mammary nodes (IMN) inclusion. In all cases, the median (25th-75th percentile) is reported. RESULTS: A total of 1221 left-sided breast cancer patients were included in this study with 1045 in the DIBH cohort. The median heart mean dose for this cohort is 1.0 Gy (0.8-1.1). For patients treated in DIBH with IMNs included (n = 422), the median of the mean LAD dose is 3.6 Gy (2.9-4.4) and, for patients treated in DIBH with IMNs excluded (n = 623), the median of the mean LAD dose is 3.2 Gy (2.5-3.8). CONCLUSIONS: Appropriate respiratory management can be utilized to achieve low dose to the LAD for the majority of patients without compromising target coverage.

Standardized flattening filter free volumetric modulated arc therapy plans based on anteroposterior width for total body irradiation.

In this work, the feasibility of using flattening filter free (FFF) beams in volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning to decrease protracted beam-on times for these treatments was investigated. In addition, a methodology was developed to generate standardized VMAT TBI treatment plans based on patient physical dimensions to eliminate plan optimization time. A planning study cohort of 47 TBI patients previously treated with optimized VMAT ARC 6 MV beams was retrospectively examined. These patients were sorted into six categories depending on height and anteroposterior (AP) width at the umbilicus. Using Varian Eclipse, clinical 40 cm × 10 cm open field arcs were substituted with 6 MV FFF. Mid-plane lateral dose profiles in conjunction with relative arc output factors (RAOF) yielded how far a given multileaf collimator (MLC) leaf must move in order to achieve a mid-plane 100% isodose for a specific control point. Linear interpolation gave the dynamic MLC aperture for the entire arc for each patient AP width category, which was subsequently applied through Python scripting. All FFF VMAT TBI plans were then evaluated by two radiation oncologists and deemed clinically acceptable. The FFF and clinical VMAT TBI plans had similar Body-5 mm D98% distributions, but overall the FFF plans had statistically significantly increased or broader Body-5 mm D2% and mean lung dose distributions. These differences are not considered clinically significant. Median beam-on times for the FFF and clinical VMAT TBI plans were 11.07 and 18.06 min, respectively, and planning time for the FFF VMAT TBI plans was reduced by 34.1 min. In conclusion, use of FFF beams in VMAT TBI treatment planning resulted in dose homogeneity similar to our current VMAT TBI technique. Clinical dosimetric criteria were achieved for a majority of patients while planning and calculated beam-on times were reduced, offering the possibility of improved patient experience.

Phase III Randomized Pair Comparison of a Barrier Film vs. Standard Skin Care in Preventing Radiation Dermatitis in Post-lumpectomy Patients with Breast Cancer Receiving Adjuvant Radiation Therapy.

Introduction Patients undergoing adjuvant radiotherapy to the breast often experience radiation dermatitis ranging from mild erythema to moist desquamation. In post-lumpectomy patients, the axilla and inframammary fold are at an increased risk for friction dermatitis. Dermatitis can impact patients' quality-of-life and may require treatment break/cessation. Our objectives are to assess the efficacy of 3M Cavilon Barrier Film (BF) in preventing and/or delaying the onset of grade-two dermatitis and reducing patient-reported sensation scores. Methods A total of 55 patients were randomized to receive BF on the medial or lateral breast. BF was applied twice weekly during treatment. Skin toxicity was evaluated weekly by a blinded clinical investigator using the Skin Toxicity Assessment Tool (STAT) and the modified Radiation Therapy Oncology Group Visual Assessment Score (RTOG VAS). On day one, baseline photographs were taken; seven-to-ten days post-treatment, patients returned for photographs, the STAT/RTOG VAS, and patient-opinion questions in the form of the global questionnaire. Results The paired analysis found BF did not significantly reduce dermatitis either during or post-treatment. However, the unpaired analysis found significantly reduced RTOG VAS on the lateral compartment during treatment (BF:0.91 vs. Control:1.21, p = 0.0408). This difference resolved post-treatment. Additionally, BF was able to reduce pruritus (p = 0.047) on the medial components and burning sensations on the lateral components (p = 0.035). There was no significant difference between the time-to-onset or proportion of patients who developed grade-two dermatitis. Conclusion In an unpaired analysis, BF significantly reduced dermatitis on the lateral compartment during treatment. Additionally, BF significantly reduced pruritus and burning sensations. A larger study using a more reliable scoring method is required to clarify the effect of BF on radiation-associated skin toxicity.

Effects of glycosylated hemoglobin levels on neutrophilic phagocytic functions.

It is well established that diabetic patients with poor glycemic control have increased susceptibility to infections, but glucose levels have not been directly associated with this increase. The assessment of the effects of glycosylated hemoglobin (A1 c) on the body's ability to fight infections may be useful directly in establishing a link between elevated blood sugar and the risk of infections. A total of 127 subjects in Heart Pilot Study (HPS), sub-study of the Adventist Health Study 2 (AHS-2) completed a lifestyle, medical and food frequency questionnaire (FFQ) at baseline between 2013 and 2014. The A1 c and phagocytic index (PI) were measured in the same blood sample and their associations were assessed using linear regression. Mean blood glucose (MBG) was estimated based on A1 c levels using a standard formula. Three levels of MBG were used to compare prediabetic and diabetic ranges to the normal range. The PI is the average number of bacteria in the cytoplasm of 50 neutrophils, manually counted under a light microscope after the whole blood was briefly exposed to a standard dose of bacteria and stained. In multivariable analysis, we found that MBG in the prediabetic (117 to137 mg/dL) and diabetic (>137 mg/dL) ranges were associated with 12.9% (ß= -0.129, 95% Cl: -0.30, 0.05) and 20.4% decrease in PI (ß= -0.204, 95% Cl: -0.592, 0.184) compared to that, observed among those with normal MBG (p for trend=0.119). Elevated MBG levels contribute a decrease in the PI among those in the prediabetic and diabetic range compared to the normal range. Although our findings were not quite statistically significant due to low power which are clinically relevant in line with observations of an increased infections among diabetics. Further research on larger populations is needed.

Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report.

BACKGROUND: The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient's myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. CASE PRESENTATION: The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. CONCLUSIONS: The timing, presentation and response of our patient's symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment.

Effects of Targeted Proton Radiation on Spinal Cord in a Porcine Model: A Pilot Study.

AIM: To determine whether proton radiation can be used to treat chronic intractable pain. The focus of this study was on the biological effects of spinal cord irradiation. MATERIALS AND METHODS: Proton radiation (0-25 Gy, single fraction) was applied to the spinal cord within L3-L5 of Yucatan mini-pigs (n=20). Skin reaction, body mass and behavior were monitored. At euthanasia, blood and spinal cord were analyzed. RESULTS: Skin morbidity was mild and overall health for the 5-20 Gy-treated groups was good based on behavior and weight gain up to 8.5-9 months post-exposure. The 25 Gy-treated animals developed hind limb weakness at 2.5-3 months and were euthanized. Radiation had a significant effect on white blood cell count (p<0.05), with the 25 Gy-treated mini-pigs having the highest number of all three major leukocyte populations. A few differences were also noted for erythrocyte parameters, but the blood chemistry panel was normal. Apoptosis in the targeted portion of the spinal cord was elevated in the 20- and 25 Gy-treated groups versus 0 Gy (p<0.05) based on the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. There was a trend (p<0.1) for a radiation effect on glial fibrillary acidic protein expression, with the highest value being found after 25 Gy. Histology showed no difference between 0 versus 25 Gy. CONCLUSION: The data demonstrated that a small segment of the spinal cord can be readily targeted using proton radiation; doses ranging from 5-20 Gy were well-tolerated in an animal model with radiosensitivity similar to humans. Future studies with a pain model should use ≤15 Gy.

Genetic and Apoptotic Changes in Lungs of Mice Flown on the STS-135 Mission in Space.

AIM: The goal of the study was to evaluate changes in lung status due to spaceflight stressors that include radiation above levels found on Earth. MATERIALS AND METHODS: Within hours after return from a 13-day mission in space onboard the Space Shuttle Atlantis, C57BL/6 mice (FLT group) were euthanized; mice housed on the ground in similar animal enclosure modules served as controls (AEM group). Lung tissue was collected to evaluate the expression of genes related to extracellular matrix (ECM)/adhesion and stem cell signaling. Pathway analysis was also performed. In addition, immunohistochemistry for stem cell antigen-1 (SCA-1), the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptosis, and staining for histological characteristics were performed. RESULTS: There were 18/168 genes significantly modulated in lungs from the FLT group (p<0.05 vs. AEM); 17 of these were up-regulated and one was down-regulated. The greatest effect, namely a 5.14-fold increase, was observed on Spock1 (also known as Spark/osteonectin), encoding a multi-functional protein that has anti-adhesive effects, inhibits cell proliferation and regulates activity of certain growth factors. Additional genes with increased expression were cadherin 3 (Cdh3), collagen, type V, alpha 1 (Col5a1), integrin alpha 5 (Itga5), laminin, gamma 1 (Lamc1), matrix metallopeptidase 14 (Mmp14), neural cell adhesion molecule 1 (Ncam1), transforming growth factor, beta induced (Tgfbi), thrombospondin 1 (Thbs1), Thbs2, versican (Vcan), fibroblast growth factor receptor 1 (Fgfr1), frizzled homolog 6 (Fzd6), nicastrin (Ncstn), nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 (Nfatc4), notch gene homolog 4 (Notch4) and vang-like 2 (Vangl2). The down-regulated gene was Mmp13. Staining for SCA-1 protein showed strong signal intensity in bronchiolar epithelial cells of FLT mice (p<0.05 vs. AEM). TUNEL positivity was also significantly higher in the FLT mice (p<0.05 vs. AEM), but no consistent histological differences were noted. CONCLUSION: The results demonstrate that spaceflight-related stress had a significant impact on lung integrity, indicative of tissue injury and remodeling.

Parotid gland follicular lymphoma lacking both cytoplasmic and surface light chains: a rare case.

Immunoglobulin light chain (LC) restriction is detected in the majority of B-cell non-Hodgkin lymphoma (B-NHL) by flow cytometric immunophenotyping (FCI) and serves as a surrogate marker of monoclonality. Even though it is known a small percentage of mature B-NHLs lacking surface LC, deficiency of both cytoplasmic and surface LCs has been reported in only three B-NHL cases. We report a primary parotid gland follicular lymphoma in a 63-year-old man and the lymphoma cells were deficient of cytoplasmic/surface LCs. Compared to previous reports, we used a more sensitive FCI method by combining both monoclonal and polyclonal anti-LC antibodies. Lacking LCs poses as a pitfall for the initial diagnosis of B-NHL, as well as for detecting minimal residual disease. It is important to be aware of this rare immunophenotypic aberrancy.

Should women younger than 40 years of age with invasive breast cancer have a mastectomy? 15-year outcomes in a population-based cohort.

PURPOSE: Optimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM). METHODS AND MATERIALS: Women aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary outcomes of breast cancer-specific survival (BCSS), overall survival (OS) and secondary outcomes of local relapse-free survival (LRFS), locoregional relapse-free survival (LRRFS), and distant relapse-free survival (DRFS) were calculated using Kaplan-Meier methods and compared between BCT and MRM cohorts using log-rank tests. A planned subgroup analysis was performed on patients considered "ideal" for BCT (ie, T1N0, negative margins and no extensive ductal carcinoma in situ) and in whom local therapy may have the largest impact on survival because of low systemic risk. RESULTS: 965 patients were identified; 616 had BCT and 349 had MRM. The median follow-up time was 14.4 years (range, 8.4-23.3 years). Overall, 15-year rates of BCSS (76.0% vs 74.1%, P=.62), OS (74.2% vs 73.0%, P=.75), LRFS (85.4% vs 86.5%, P=.95), LRRFS (82.2% vs 81.6%, P=.61), and DRFS (74.4% vs 71.6%, P=.40) were similar between the BCT and MRM cohorts. In the "ideal" for BCT subgroup, there were 219 BCT and 67 MRM patients with a median follow-up time of 15.5 years. The 15-year BCSS (86.1% vs 82.9%, P=.57), OS (82.6% vs 82.9%, P=.89), LRFS (86.2% vs 84.2%, P=.50), LRRFS (83.1% vs 78.3%, P=.24), and DRFS (84.8% vs 79.1%, P=.17) were similar in the BCT and MRM cohorts. CONCLUSIONS: This population-based analysis with long-term follow-up confirmed that women younger than 40 years treated with BCT had similar 15-year outcomes compared with MRM. Young age alone is not a contraindication to BCT.

Management of high-grade gliomas in the elderly.

The incidence of glioblastoma (GBM) has been increasing over the past several decades with majority of this increase occurring in patients older than 70 years. In spite of the growing body of evidence in this area, it is still unclear as to the optimal management of elderly patients with GBM. The elderly are a heterogeneous population with a range of comorbid conditions, and functional, cognitive, and physiological changes, and ideally treatment decisions should be made in the context of a comprehensive geriatric assessment. Patients with a poor performance status or assessed as "frail" might be considered for less aggressive therapy such as hypofractionated radiotherapy or single-agent temozolomide, whereas those with a good functional status may still benefit from maximum resection followed by combined radiation and chemotherapy. Recent randomized trials suggest molecular markers such as O(6)-methylguanine-DNA-methyltransferase promoter methylation testing could help guide these decisions, particularly when considering monotherapy with temozolomide vs radiotherapy. Ongoing studies seek to clarify the role of concurrent treatment in this population. Clinical judgment and discussion with patients and families, weighing all the options, are necessary in each case. Ultimately, patients and the neuro-oncology community should be encouraged to participate in clinical trials focused specifically on caring for the elderly patient with GBM.