Ionizing radiation is an important treatment modality for a variety of malignant conditions. However, development of radiation-induced skin changes is a significant adverse effect of radiation ...therapy (RT). Cutaneous repercussions of RT vary considerably in severity, course, and prognosis. When they do occur, cutaneous changes to RT are commonly graded as acute, consequential-late, or chronic. Acute reactions can have severe sequelae that impact quality of life as well as cancer treatment. Thus, dermatologists should be informed about these adverse reactions, know how to assess their severity and be able to determine course of management. The majority of measures currently available to prevent these acute reactions are proper skin hygiene and topical steroids, which limit the severity and decrease symptoms. Once acute cutaneous reactions develop, they are treated according to their severity. Treatments are similar to those used in prevention, but incorporate wound care management that maintains a moist environment to hasten recovery. Chronic changes are a unique subset of adverse reactions to RT that may develop months to years following treatment. Chronic radiation dermatitis is often permanent, progressive, and potentially irreversible with substantial impact on quality of life. Here, we also review the etiology, clinical manifestations, pathogenesis, prevention, and management of late-stage cutaneous reactions to radiotherapy, including chronic radiation dermatitis and radiation-induced fibrosis.
Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains ...variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group.
A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants.
Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate.
This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
To determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life for selected ...patients with limited-disease small-cell lung cancer (LD SCLC).
Patients with LD SCLC who achieved a complete response after chemotherapy and thoracic irradiation were eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily fractions (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy underwent a secondary randomization between daily 18 fractions (Arm 2) and twice-daily 24 fractions (Arm 3). Enrolled patients participated in baseline and follow-up neuropsychological test batteries along with quality-of-life assessments.
A total of 265 patients were accrued, with 131 in Arm 1, 67 in Arm 2, and 66 in Arm 3 being eligible. There are 112 patients (42.2%) alive with 25.3 months of median follow-up. There were no significant baseline differences among groups regarding quality-of-life measures and one of the neuropsychological tests, namely the Hopkins Verbal Learning Test. However, at 12 months after PCI there was a significant increase in the occurrence of CNt in the 36-Gy cohort (p=0.02). Logistic regression analysis revealed increasing age to be the most significant predictor of CNt (p=0.005).
Because of the increased risk of developing CNt in study patients with 36 Gy, a total PCI dose of 25 Gy remains the standard of care for patients with LD SCLC attaining a complete response to initial chemoradiation.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Delays in time to treatment initiation (TTI) with definitive radiation therapy (RT) or chemotherapy and RT (CRT) for cervical cancer could lead to poorer outcomes. This study investigates disparities ...in TTI and the impact of TTI on overall survival (OS).
Adult women with non-metastatic cervical squamous cell carcinoma diagnosed between 2004 and 2014, treated with definitive RT or CRT, and reported to the National Cancer Database were included. TTI was defined as days from diagnosis to start of RT or CRT. The impact of TTI on OS in patients treated with concurrent CRT which included brachytherapy was then assessed.
Overall, 14,924 patients were included (84.7% CRT, 15.3% RT). TTI was significantly longer for Non-Hispanic Black (NHB) (RR, 1.14; 95% CI, 1.11 to 1.18) and Hispanic women (RR, 1.19; 95% CI, 1.15 to 1.24) compared to Non-Hispanic White (NHW) women. Expected TTI (eTTI) for NHW, NHB, and Hispanic women were 38.1, 45.2, and 49.4days. eTTI rose from 36.2days in 2004 to 44.3days by 2014. Intensity-modulated radiation therapy (IMRT) was associated with increased eTTI of 46.5days versus 40.0days for non-IMRT. Longer TTI was not associated with inferior OS in patients treated with concurrent CRT.
Delays in starting RT/CRT for cervical cancer increased from 2004 to 2014. Delays disproportionately affect NHB and Hispanic women. However, increased TTI was not associated with increased mortality for women receiving CRT. Further study of TTI's impact on other endpoints is warranted to determine if TTI represents an important quality indicator.
•Time to treatment initiation for cervical cancer has increased between 2004 and 2014.•There are significant disparities in TTI for cervical cancer.•Hispanic and Non-Hispanic Black women have the longest delays to treatment.•TTI is not associated with OS.•Further study into TTI's impact on other endpoints is warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core ...Quality of Life Questionnaire (EORTC QLQ-C30).
Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline.
Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively).
In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
The impact of preoperative glycemic control on the risk of adverse perioperative outcomes in diabetic patients undergoing lower extremity bypass (LEB) surgery is not well-understood. We determined ...whether higher preoperative hemoglobin A1c (HbA1c) levels are associated with an increased risk of major adverse limb events, major adverse cardiovascular events, and mortality in diabetic patients undergoing infrainguinal LEB.
A retrospective review of all infrainguinal LEB surgeries in the Vascular Quality Initiative registry from January 2012 to February 2017 was performed. Only surgeries performed on diabetic patients with complete demographic and clinical data, including HbA1c value at the time of LEB, were included for analysis (n = 7727). Entries were stratified according to the following HbA1c levels: 6 or less (n = 1087), greater than 6 to 7 or less (n = 2137), greater than 7 to 8 or less (n = 1657), and greater than 8 (n = 2846). Multivariate logistic regression was used to determine the association of preoperative HbA1c levels on the risk of in-hospital major adverse limb events (above ankle amputation, loss of primary graft patency), major adverse cardiovascular events (myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia), and mortality.
The number of surgeries complicated by adverse limb and cardiovascular events were 356 (4.6%) and 1314 (17.0%), respectively. There were 72 in-hospital deaths (0.9%). After adjustment for clinical and demographic variables, patients with high HbA1c values (≥8%) were at an increased risk of adverse limb events (odds ratio OR, 1.37; 95% confidence interval CI, 1.01-1.86) compared with those with a normal HbA1c (>6% to ≤7%). High HbA1c values were not associated with an increased risk of cardiovascular events (OR, 1.07; 95% CI, 0.81-1.43) or mortality (OR, 1.57; 95% CI, 0.83-3.03). Patients with low HbA1c values (≤6%) did not experience a significantly higher risk for any of the three outcomes. In a stratified analysis, the association of high HbA1c values with adverse limb events was only present in those presenting without critical limb ischemia (OR 1.82; 95% CI, 1.05-3.16).
Poor preoperative glycemic control in diabetic individuals undergoing infrainguinal LEB, particularly in those without critical limb ischemia, is associated with an increased risk of in-hospital limb events. Further study should evaluate whether improved efforts to identify individuals with poorly controlled diabetes and subsequent interventions to better optimize glycemic control during the preoperative period improve limb outcomes after LEB.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally ...advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary Background The optimum dose of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC) is unknown. A meta-analysis suggested that the incidence of brain ...metastases might be reduced with higher PCI doses. This randomised clinical trial compared the effect of standard versus higher PCI doses on the incidence of brain metastases. Methods Between September, 1999, and December, 2005, 720 patients with limited-stage SCLC in complete remission after chemotherapy and thoracic radiotherapy from 157 centres in 22 countries were randomly assigned to a standard (n=360, 25 Gy in 10 daily fractions of 2·5 Gy) or higher PCI total dose (n=360, 36 Gy) delivered using either conventional (18 daily fractions of 2 Gy) or accelerated hyperfractionated (24 fractions in 16 days with two daily sessions of 1·5 Gy separated by a minimum interval of 6 h) radiotherapy. All of the treatment schedules excluded weekends. Randomisation was stratified according to medical centre, age (≤60 and >60 years), and interval between the start of induction treatment and the date of randomisation (≤90, 91–180, and >180 days). Eligible patients were randomised blindly by the data centre of the Institut Gustave Roussy (PCI99-01 and IFCT) using minimisation, and by the data centres of EORTC (EORTC ROG and LG) and RTOG (for CALGB, ECOG, RTOG, and SWOG), both using block stratification. The primary endpoint was the incidence of brain metastases at 2 years. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov number NCT00005062. Findings Five patients in the standard-dose group and four in the higher-dose group did not receive PCI; nonetheless, all randomised patients were included in the effectiveness anlysis. After a median follow-up of 39 months (range 0–89 months), 145 patients had brain metastases; 82 in the standard-dose group and 63 in the higher-dose group. There was no significant difference in the 2-year incidence of brain metastases between the standard PCI dose group and the higher-dose group, at 29% (95% CI 24–35) and 23% (18–29), respectively (hazard ratio HR 0·80 95% CI 0·57–1·11, p=0·18). 226 patients in the standard-dose group and 252 in the higher-dose group died; 2-year overall survival was 42% (95% CI 37–48) in the standard-dose group and 37% (32–42) in the higher-dose group (HR 1·20 1·00–1·44; p=0·05). The lower overall survival in the higher-dose group is probably due to increased cancer-related mortality: 189 patients in the standard group versus 218 in the higher-dose group died of progressive disease. Five serious adverse events occurred in the standard-dose group versus zero in the higher-dose group. The most common acute toxic events were fatigue (106 30% patients in the standard-dose group vs 121 34% in the higher-dose group), headache (85 24% vs 99 28%), and nausea or vomiting (80 23% vs 101 28%). Interpretation No significant reduction in the total incidence of brain metastases was observed after higher-dose PCI, but there was a significant increase in mortality. PCI at 25 Gy should remain the standard of care in limited-stage SCLC. Funding Institut Gustave-Roussy, Association pour la Recherche sur le Cancer (2001), Programme Hospitalier de Recherche Clinique (2007). The European Organisation for Research and Treatment of Cancer (EORTC) contribution to this trial was supported by grants 5U10 CA11488-30 through 5U10 CA011488-38 from the US National Cancer Institute.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at ...an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment.
We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk.
We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12–2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67–4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81–10.26; deep 1/3, HR 7.05, CI 2.99–16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25–17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI.
Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
•Adenocarcinoma is a distinct cervical cancer subtype and treatment should be based on data specific to this subtype.•Risk factors for recurrence differ for squamous cell carcinoma and adenocarcinoma of the cervix.•For adenocarcinoma of the cervix, tumor size is the risk factor associated with the highest risk of recurrence.•For squamous cell carcinoma, depth of invasion is the risk factor associated with the highest risk of recurrence.•Histology-specific nomograms accurately and linearly represent risk of recurrence for squamous cell and adenocarcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The heart transplantation policy change (PC) has improved outcomes in high‐acuity (Old 1A, New 1–3) patients, but the effect on low‐priority (Old 1B/2, New 4–6) patients is unknown. We sought to ...determine if low‐priority patient outcomes were compromised by benefits to high‐priority patients by evaluating for interaction between PC and priority status (PS). We included adult first‐time heart transplant candidates and recipients from the UNOS registry during a 19‐month period before and after the PC. We compared clinical characteristics and performed competing risks and survival analyses stratified by PC and PS. There was a dependence of PC and PS on waitlist death/deterioration with an interaction sub‐distribution hazard ratio (adjusted sdHR) of 0.59 (0.45–0.78), p‐value < .001. There was a trend toward a benefit of PC on waitlist death/deterioration (adjusted sdHR: 0.86 0.73–1.01; p = .07) and an increase in heart transplantation (adjusted sdHR: 1.08 1.02–1.14, p = .007) for low‐priority patients. There was no difference in 1‐year post‐transplant survival (log‐rank p = .22) when stratifying by PC and PS. PC did not negatively affect waitlisted or transplanted low‐priority patients. High‐priority, post‐PC patients had a targeted reduction in waitlist death/deterioration and did not come at the expense of worse post‐transplant survival.
The updated heart allocation policy is associated with improved waitlist outcomes in high‐acuity patients, no significant difference in waitlist outcomes for low‐acuity patients, and no change in one‐year post‐transplant survival.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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