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PURPOSE: To determine the current U.S. practice patterns of analgesia (AG) and anesthesia (AS) for gynecologic brachytherapy (BT) procedures. METHODS AND MATERIALS: A 27-item survey created with expertise from five brachytherapists was distributed electronically to 90 U.S. Radiation Oncology academic programs and publicized on social media and at two national meetings during June-October 2023. RESULTS: Forty-one responses were received (46%). Fifty-four percent identified as female, 66% Caucasian and 85% non-Hispanic/Latino ethnicity. Forty nine percent utilize a BT suite +/- CT simulator alone, 39% the operating room +/- BT suite or CT simulator or other location, 10% CT simulation room alone, and 2% clinic exam room. Thirty four percent utilize general anesthesia alone (GA) for intracavitary BT (n=41), 20% conscious sedation (CS) alone, 10% oral analgesia (OA) alone, and 9% spinal or epidural AS alone, and 27% combination. Among those performing hybrid BT (n=25), 40% use GA alone, 16% use CS alone, 12% epidural or spinal AS alone, and 4% OA alone, and 28% combination. For template interstitial BT (n=25), 44% use GA alone, 48% epidural alone or in combination with other AS, and 8% CS alone. Twenty-two percent of respondents provide AG or AS during applicator placement only, while 32% provide it during placement, planning, treatment, and removal. The most common reasons for not using CS or GA were lack of anesthesia resources and clinician preference. Seventy-three percent reported the belief that patients suffer from post-traumatic stress disorder (PTSD) symptoms after BT. However, 68% reported not using techniques to alleviate BT related emotional distress. CONCLUSIONS: Many U.S. brachytherapists report using GA, CS or epidural AS, yet 10% are using only OA and 22% offer AG/AS only during applicator placement. Furthermore, a majority of respondents believe PTSD symptoms can occur after BT, but few offer any intervention. AS resources and clinician preference should be targeted for expansion of higher quality care.
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We report the case of a female neonate admitted to the neonatal ICU with a rapid, narrow-complex tachyarrhythmia determined to be supraventricular tachycardia. Multimodality imaging and genetic testing confirmed a diagnosis of tuberous sclerosis complex with multiple cardiac rhabdomyomas. At 13 days of age, the patient was readmitted, exhibiting recurrent supraventricular tachycardia non-responsive to first-line treatment. Management required triple-drug therapy, whereafter the patient remained stable without recurrences. This is a rare report of supraventricular tachycardia in a functionally normal heart with the occurrence of supraventricular tachycardia due to structural abnormalities, with the possibility of multiple concealed accessory pathways.
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Background: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC. Case reports: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up. Conclusion: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.
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BACKGROUND/OBJECTIVE: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. METHODS: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1-2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. RESULTS: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7- 54.8 months). CONCLUSIONS: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. TRIAL REGISTRATION: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).
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Neoplasias de la Mama , COVID-19 , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Cuidados Intraoperatorios , Mastectomía Segmentaria/métodos , Recurrencia Local de Neoplasia/cirugía , Persona de Mediana EdadRESUMEN
This retrospective pooled analysis aims to identify factors predicting relapse despite a pathologic complete response (pCR) in patients with breast cancer (BC). 2066 patients with a pCR from five neoadjuvant GBG/AGO-B trials fulfill the inclusion criteria of this analysis. Primary endpoint is disease-free survival (DFS); secondary endpoints is distant DFS (DDFS) and overall survival (OS). After a median follow-up of 57.6 months, DFS is significantly worse for patients with positive lymph nodes (cN+ vs cN0 hazard ratio [HR] 1.94, 95%CI 1.48-2.54; p < 0.001). In patients with triple-negative tumors, lobular histology (lobular vs other HR 3.55, 95%CI 1.53-8.23; p = 0.003), and clinical nodal involvement (cN+ vs cN0 HR 2.45, 95%CI 1.59-3.79; p < 0.001) predict a higher risk of DFS events. Patients with HER2-positive cT3/4 tumors have a significantly higher risk of relapse (cT3/4 vs cT1 HR 2.07, 95%CI 1.06-4.03; p = 0.033). Initial tumor load and histological type predict relapse in patients with a pCR.
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Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department. Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ2, t tests, and logistic regression were used to assess predictors of FT. Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT (P = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P = .019) in multivariate analysis. Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations.
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BACKGROUND: We investigate the impact of gender, race, and socioeconomic status on the diagnosis and management of bladder cancer in the United States. METHODS: We utilized the National Cancer Database to stratify cases of urothelial cell carcinoma of the bladder as early (Tis, Ta, T1), muscle invasive (T2-T3, N0), locally advanced (T4, N1-3), and metastatic. Multivariate binomial and multinomial logistic regression analyses identified demographic characteristics associated with stage at diagnosis and receipt of cancer-directed therapies. Odds ratios (OR) are reported with 95% confidence intervals. RESULTS: After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases from 2004-2016. Relative to diagnosis at early stage, the strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included Black race (OR = 1.19 [1.15-1.23], OR = 1.49 [1.40-1.59], OR = 1.66 [1.56-1.76], respectively), female gender (OR = 1.21 [1.18-1.21], OR = 1.16 [1.12-1.20], and OR = 1.34 [1.29-1.38], respectively), and uninsured status (OR = 1.22 [1.15-1.29], OR = 2.09 [1.94-2.25], OR = 2.57 [2.39-2.75], respectively). Additional demographic factors associated with delayed diagnosis included older age, treatment at an academic center, Medicaid insurance and patients from lower income/less educated/more rural areas (all p < 0.01). Treatment at a non-academic center, older age, women, Hispanic and Black patients, lower income and rural areas were all less likely to receive cancer-directed therapies in early stage disease (all p < 0.01). Women, older patients, and Black patients remained less likely to receive treatment in muscle invasive, locally advanced, and metastatic disease (all p < 0.01). CONCLUSION: Black race was the strongest independent predictor of delayed diagnosis and substandard treatment of bladder cancer.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Femenino , Estados Unidos/epidemiología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/patología , Medicaid , Hispánicos o Latinos , Población Negra , Disparidades en Atención de SaludRESUMEN
Background: Partial breast irradiation with Intra-operative radiotherapy (IORT) has become a popular management option as opposed to whole breast radiation using external beam radiotherapy for breast cancer patients. While previous studies have highlighted the use of IORT in breast cancer patients, there is a scarcity of literature on the use of IORT in those who also have ipsilateral pacemakers. Thus, the aim of our case report is to highlight the applicability of IORT in breast cancer patients who also have a pacemaker. Case Reports: Two female patients with an implanted dual-chamber pacemaker presented with a diagnosis of left-sided invasive ductal carcinoma on mammogram. Mammography of the left breast revealed a 10 mm and 7 mm spiculated mass, respectively, further confirmed with an ultrasound-guided core biopsy that was conclusive of clinical Stage I T1 N0 grade 2, ER +, PR + Her2 - invasive ductal carcinoma. They met our eligibility criteria for IORT, which is being performed as a registry trial. These patients underwent a wide excision lumpectomy along with IORT. Conclusion: Our findings underscore the successful use of targeted IORT for breast-conserving surgery in a patient with invasive ductal carcinoma and pacemaker, hence eliminating the necessity for relocating pacemaker surgeries in these patients. Furthermore, no device failure or malfunction for the pacemaker was recorded before, during, or after the surgery, demonstrating the safety of using IORT in patients with preinstalled pacemaker despite a lack of evidence on safe radiation dosage or manufacturer guidelines. Nonetheless, the effects of IORT on pacemaker < 10 cm were not studied in our patients and further clinical studies are recommended to reinforce the applicability and safe distance of IORT in breast cancer patients with pacemaker.
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PURPOSE: The purpose of this technical note was to investigate correlation of total reference air-kerma (TRAK) with volume enclosed by the prescription isodose surface in vaginal cylinder high-dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: Treatment plans of 175 gynecological cancer patients treated at our institution with iridium-192 (192Ir) HDR brachytherapy using a single-channel vaginal cylinder applicator were retrospectively reviewed. Applicator size in diameter ranged from 20 mm to 40 mm. Treatment length ranged from 30 mm to 90 mm (median, 50 mm). Brachytherapy fractional dose was 5 Gy (DoseRef) prescribed to 5 mm distance from cylinder surface. Parameters TRAK (cGy), source activity during treatment (Ci), total treatment time (s), and prescription isodose surface volume ISVRef (cm3) were recorded from individual treatment plans. In each case, vaginal tissue volume (VVT) enclosed by prescription isodose was calculated by subtracting cylinder volume enclosed by the prescription isodose from ISVRef. RESULTS: Total reference air-kerma correlated with the total volume enclosed by the prescription isodose via ISVRef = 4768 × (TRAK/DoseRef)1.47. TRAK related linearly to the volume of vaginal tissue enclosed by the prescription dose via VVT = ((138.3 × TRAK) - 8.2). Secondarily, TRAK related to the treatment time through time (s) = 882 (s/cGy) × TRAK (cGy), where 882 is (1/air-kerma strength) for 10 Ci apparent activity of 192Ir source. CONCLUSIONS: The correlation of TRAK to the vaginal tissue volume encompassed by the prescription dose surface yields a useful predictive equation. The TRAK treatment time relationship enables quick verification of planned treatment time by knowing TRAK in any HDR brachytherapy application.
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IMPORTANCE: Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking. OBJECTIVE: To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer. DESIGN, SETTING, AND PARTICIPANTS: The Randomized European Celecoxib Trial (REACT) was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany testing 2 years of adjuvant celecoxib vs placebo among 2639 patients recruited between January 19, 2007, and November 1, 2012, with follow-up 10 years after treatment completion. Eligible patients had completely resected breast cancer with local and systemic therapy according to local practice. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. Randomization was in a 2:1 ratio between celecoxib or placebo. Statistical analysis was performed from May 5, 2019, to March 5, 2020. INTERVENTIONS: Patients received celecoxib, 400 mg, or placebo once daily for 2 years. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population using Cox proportional hazards regression and log-rank analysis. Follow-up is complete. RESULTS: A total of 2639 patients (median age, 55.2 years [range, 26.8-86.0 years]) were recruited; 1763 received celecoxib, and 876 received placebo. Most patients' tumors (1930 [73%]) were estrogen receptor positive or progesterone receptor positive and ERBB2 negative. A total of 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors. At a median follow-up of 74.3 months (interquartile range, 61.4-93.6 years), DFS events had been reported for 487 patients (19%): 18% for those who received celecoxib (n = 323; 5-year DFS rate = 84%) vs 19% for those who received placebo (n = 164; 5-year DFS rate = 83%); the unadjusted hazard ratio was 0.97 (95% CI, 0.80-1.17; log-rank P = .75). Rates of toxic effects were low across both treatment groups, with no evidence of a difference. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, patients showed no evidence of a DFS benefit for 2 years' treatment with celecoxib compared with placebo as adjuvant treatment of ERBB2-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS benefit, but further studies would be required to test this possibility. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02429427 and isrctn.org Identifier: ISRCTN48254013.
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Neoplasias de la Mama , Celecoxib , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Celecoxib/efectos adversos , Celecoxib/uso terapéutico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Supervivencia sin ProgresiónRESUMEN
INTRODUCTION: Viral infections have been described as triggers for Kawasaki Disease (KD), a medium vessel vasculitis that affects young children. Akin to the H1N1 pandemic in 2009, there is a similar rise in the incidence of KD in children affected with Coronavirus disease 2019 (COVID-19). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been reported to induce an exaggerated systemic inflammatory response resulting in multi-organ involvement, particularly initiated with pulmonary parenchymal damage. This review article will discuss KD-like manifestations in COVID-19 patients in the pediatric cohort. METHODOLOGY: Search terms "Kawasaki" "COVID-19" "SARS-COV-2" "PIM-TS" and "MIS-C" were used to look for relevant articles in PubMed and Google Scholar published in the last 5 years. RESULTS: There is some evidence to suggest that SARS-CoV-2 stimulates dysfunctional and hyperactive immune reactions mimicking KD in young patients. CONCLUSIONS: Therapeutic options, both investigational and repurposed, include intravenous immunoglobulins, steroids and anticoagulation. More studies are required to evaluate the effectiveness of these treatment options.
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COVID-19/complicaciones , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/virología , SARS-CoV-2RESUMEN
PURPOSE: To report the impact of dose and tumor volume metrics at brachytherapy on outcomes for locally advanced cervical cancer treated with tandem and ovoids intracavitary/interstitial brachytherapy. MATERIAL AND METHODS: FIGO stage IB1-IIIB locally advanced cervical cancer treated with intracavitary/interstitial brachytherapy via a tandem and ovoids hybrid applicator were analyzed. Median high-risk clinical target volume (HR-CTV), rate of tumor volume reduction, EQD2 D90, organ at risk doses, and outcomes were recorded. Univariable and multivariable Cox regression was applied for survival analysis, and logistic regression was used for toxicity analysis. RESULTS: Seventy-one patients were identified. Median follow-up was 24.9 months, with a 2-year local control of 83.6%, loco-regional control of 72.0%, and overall survival of 88.6%. Median HR-CTV D90 was 87.4 Gy (IQR = 85.7-90.2). Median HR-CTV D90 > 90 Gy10 showed a trend toward improved local control (LC) (p = 0.19). Median HR-CTV was 37.9 cm3, and median V100 was 86.5%. A median HR-CTV of ≥ 40 cm3 demonstrated worse loco-regional control (LRC) (p = 0.018) and progression-free survival (p = 0.021). Two-year LC and LRC for stage IIB patients with a median HR-CTV < 40 cm3 were significantly improved as compared to ≥ 40 cm3 at 100% and 71.8%, respectively (p = 0.019) and 100% and 56.5%, respectively (p = 0.001). However, this trend was not statistically significant for stage IIIB patients. Higher percent per day reduction in HR-CTV during brachytherapy showed improved LRC (p = 0.045). Four percent of patients experienced acute grade 3 genitourinary toxicity, 1% late grade 3 genitourinary and 1% late grade 3 gastrointestinal toxicity. CONCLUSIONS: Tandem and ovoids intracavitary/interstitial brachytherapy provides satisfactory outcomes with modest toxicity. Higher HR-CTV D90 coverage demonstrated a trend toward improved tumor control. Tumor volume based on median HR-CTV ≥ 40 cm3 at brachytherapy was prognostic for poor outcomes, even within initial FIGO stage groups warranting caution.
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INTRODUCTION: High-risk prostate cancer is associated with poorer overall survival (OS) and biochemical control compared to more favorable risk groups. External beam radiation therapy (EBRT) is widely used; however, outcomes data are limited with respect to time elapsed between diagnosis and initiation of EBRT. METHODS: The National Cancer Database was queried from 2004 to 2015 for patients diagnosed with high-risk adenocarcinoma of the prostate who received androgen deprivation therapy (ADT) and definitive EBRT. Logistic regression was utilized to determine covariates associated with missing EBRT treatments. OS was analyzed using multivariate cox proportional hazards models and propensity score matching. RESULTS: 9,610 patients met inclusion criteria with median follow-up of 40.6 months and median age of 72 years. Median PSA was 8.7 and median EBRT dose was 78 Gy. ADT was initiated at a median of 36 days and EBRT at a median of 63 days post-diagnosis. Median number of prolonged treatment days was 2.2. Black race (OR: 1.40; p < 0.01), treatment at a community clinic (OR: 1.32; p < 0.01), and living in an urban/densely populated area were associated with prolonged treatment. Time elapsed between ADT and EBRT > 74 days (HR: 1.20; p = 0.01) and prolonged treatment>3 days of EBRT (HR: 1.26; p = 0.005) were associated with an increased hazard of death. The 5-year OS was 79.6% and 82.9% for patients with prolonged treatment of 3 days or more of EBRT and those missing 3 days or less, respectively (p = 0.0006). CONCLUSION: In this hypothesis-generating study, prolonged treatment delays and missing three or more EBRT treatments was associated with poorer OS in patients with high-risk adenocarcinoma of the prostate.
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BACKGROUND: Information on deaths occurring during oncological clinical trials has never been systematically assessed. Here, we examine the incidence of death and the profile of patients who died during randomized clinical breast cancer (BC) trials. METHODS: Information on fatal events during German Breast Group (GBG) led BC trials was prospectively captured. Data were derived from the trial databases and death narratives. All deaths were evaluated for possible causes, underlying conditions, treatment relatedness, time point and rate of autopsies. RESULTS: From 12/1996 to 01/2017, 23,387 patients were treated within 32 trials. Of those 88 (0.4%) died on therapy within 17 trials. Median age was 64 [range 35-84] years, 63.2% of patients had a body mass index (BMI) ≥ 25 kg/m2; 65.9% 1-3 and 22.7% ≥ 4 comorbidities; 61.4% 1-2 cardiovascular risk factors (CRFs); 26.4% took > 3 drugs; 81.7% had ECOG 0; 50.0% stage III, 76.7% luminal BC. The main causes of death were infection (38.6%; of those, 82.3% sepsis, 17.6% pneumonia), heart failure (14.8%), and pulmonary embolism (13.6%). Fatal events mainly occurred within the first 4 therapy cycles (55.7%), in the investigational arm (66.7%) and under anthracycline-taxane-based chemotherapy (51.1%). A relationship with the treatment was declared in 27.3% of the cases. An autopsy was performed in 13.6% of patients. CONCLUSIONS: Death during study treatment was mainly related to infections, and patients with advanced disease, high BMI, underlying comorbidities, CRFs and concomitant medications. If considered for study participation these patients need careful monitoring due to their higher risk for death on study.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Autopsia , Índice de Masa Corporal , Neoplasias de la Mama/patología , Hidrocarburos Aromáticos con Puentes/efectos adversos , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Comorbilidad , Femenino , Alemania , Insuficiencia Cardíaca/complicaciones , Humanos , Persona de Mediana Edad , Seguridad del Paciente , Neumonía/complicaciones , Estudios Prospectivos , Embolia Pulmonar/complicaciones , Factores de Riesgo , Sepsis/complicaciones , Taxoides/efectos adversos , Taxoides/uso terapéuticoRESUMEN
PURPOSE: Using in vivo measurements from optically stimulated luminescence dosimeters (OSLDs) to develop and validate a prediction model for estimating the skin dose received by patients undergoing breast intraoperative radiation therapy (IORT). METHODS AND MATERIALS: IORT was performed using INTRABEAM-600 with spherical applicators placed in the lumpectomy cavity. Ultrasound skin bridge measurements were used to determine the applicator-to-skin distance, with OSLDs placed to measure the skin surface dose at the corresponding points. The OSLD response was calibrated for the 50 kVp INTRABEAM-600 output. Models were fit to describe the dose fall-off with increasing applicator-to-skin distance and the best fitting model was chosen for estimating skin dose. RESULTS: Twenty four patients with 25 lumpectomy cavities were included, and the average skin dose recorded was 1.18 Gy ± 0.88 Gy, ranging from 0.17 Gy to 4.77 Gy, with an average applicator-to-skin distance of 19.9 mm ± 5.1 mm. An exponential-plateau model was found to best describe the dose fall-off with a root-mean-square error of 0.73. This model was then validated prospectively using skin dose measurements from five consecutive patients. Validation measurements were well within the 95% prediction limits of the model, with a root-mean-square error of 0.52, showing that the prediction model accurately estimates skin dose using ultrasound skin bridge measurements. CONCLUSIONS: This prediction model constitutes a useful tool for estimating the skin dose received during breast lumpectomy IORT. The model and accompanying 95% confidence intervals can be used to establish a minimum allowable skin bridge distance, effectively limiting the maximum allowable skin dose.
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Braquiterapia/métodos , Neoplasias de la Mama/radioterapia , Dosimetría in Vivo/métodos , Piel/efectos de la radiación , Neoplasias de la Mama/cirugía , Calibración , Femenino , Humanos , Periodo Intraoperatorio , Mastectomía Segmentaria , Persona de Mediana Edad , Modelos Biológicos , Órganos en Riesgo/efectos de la radiación , Dosis de Radiación , Dosificación Radioterapéutica , Radioterapia Adyuvante/métodos , Dosimetría Termoluminiscente/métodos , Ultrasonografía/métodosRESUMEN
PURPOSE: Ki-67 has been clinically validated for risk assessment in breast cancer, but the analytical validation and cutpoint-definition remain a challenge. Intraclass correlation coefficients (ICCs) are a statistical parameter for Ki-67 interobserver performance. However, the maximum degree of variance among pathologists allowed for meaningful biomarker results has not been defined. METHODS: Different amounts of variance were added to central pathology Ki-67 data (n = 9069) from three cohorts (IBCSGVIII + IX, BIG1-98, GeparTrio) by simulation of 4500 evaluations for each cohort, which were grouped by ICCs, ranging from excellent (ICC = 0.9) to poor concordance (ICC = 0.1). Endpoints were disease-free survival (DFS) and pathological complete response (pCR, GeparTrio). RESULTS: Ki-67 was a significant continuous prognostic marker for DFS over a wide range of cutpoints between 8% and 30% in all three cohorts. In our modelling approach, Ki-67 was a stable prognostic marker despite increased interpathologist variance. Even for a poor ICC of 0.5, one or more significant Ki-67 cutoffs were detected in 86.8% (GeparTrio), 92.4% (IBCSGVIII + IX) and 100% of analyses (BIG1-98). Similarly, in GeparTrio, even with an extremely low ICC of 0.2, 99.6% of analyses were significant for pCR. CONCLUSIONS: Our study shows that Ki-67 is a continuous marker which is extremely robust to pathologist variation. Even if only 50% of variance is attributable to true Ki-67-based proliferation (ICC = 0.5), this information is sufficient to obtain statistically significant differences in clinical cohorts. This stable performance explains the observation that many Ki-67 studies achieve significant results despite relevant interobserver variance and points to a high clinical validity of this biomarker. For clinical decisions based on analysis of individual patient data, ongoing efforts to further reduce interobserver variability, including ring trials and standardized guidelines as well as image analysis approaches, should be continued.
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Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Antígeno Ki-67/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Ensayos Clínicos como Asunto , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Modelos Teóricos , Terapia Neoadyuvante , Metástasis de la Neoplasia , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Pronóstico , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
OBJECTIVE: We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation "sandwiched" between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival. METHODS: Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities. RESULTS: One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles. CONCLUSIONS: The long-term follow-up in this study demonstrates that "sandwich" therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal "sandwich" therapy should be considered in all USC patients who have undergone complete surgical resection and staging.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/radioterapia , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/radioterapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Quimioterapia Adyuvante , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Supervivencia sin Progresión , Radioterapia Adyuvante , Tasa de Supervivencia , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugíaRESUMEN
Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
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Neoplasias de la Mama/tratamiento farmacológico , Preservación de la Fertilidad/métodos , Hormona Liberadora de Gonadotropina/agonistas , Tratamientos Conservadores del Órgano/métodos , Ovario/efectos de los fármacos , Insuficiencia Ovárica Primaria/prevención & control , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Premenopausia , Insuficiencia Ovárica Primaria/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
INTRODUCTION: Radiation recall dermatitis (RRD) is a phenomenon that occurs in previously irradiated areas shortly after administration of a chemotherapeutic agent. As the use of sorafenib expands, the incidence of radiation recall dermatitis induced by sorafenib will likely increase. Here, we report on a patient who developed RRD and describe his clinical characteristics along with a review of the literature. CASE PRESENTATION: Our patient was treated with palliative radiation therapy (RT) to a painful metastatic hepatocellular carcinoma lesion in the right forearm. He completed his radiation course with grade 1 dermatitis, which had resolved by the time he was started on sorafenib 400 mg twice daily 7 days afterwards. On the 21st day after RT, he presented with desquamation and erythema in the previously irradiated area of the right forearm, consistent with RRD. The sorafenib was discontinued and his symptoms subsequently resolved with conservative topical management. CONCLUSIONS: Although the pathophysiologic mechanism of sorafenib-related radiation recall dermatitis remains to be investigated, practitioners should be aware of its presence and management in order to improve clinical outcomes.