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BACKGROUND Our objectives were to evaluate geographic access to lung cancer treatment modalities in North Carolina and to characterize how practice patterns are changing over time. We hypothesized that rural patients would be less likely to undergo treatment compared to urban patients, with widening disparities over time.METHODS We identified patients with Stage I non-small cell lung cancer (NSCLC) from 2006 to 2015 using the North Carolina Central Cancer Registry linked with Medicaid, Medicare, and private insurance claims. The primary outcome was first-course treatment: surgery, radiation, or no treatment. Calendar years were split into earlier (2006-2010) and later (2011-2015) periods. We estimated the adjusted odds ratio (OR) of rural/urban status and time period with 1) surgery and 2) any treatment (surgery or radiation) using multivariable logistic regression.RESULTS Among 5504 patients, 3206 (58%) underwent surgery as initial therapy, 1309 (24%) received radiation as initial therapy, and 989 (18%) had no therapy. There were no rural-urban disparities in treatment patterns. For rural and urban patients, the odds of surgery decreased over time and the odds of radiation increased. We also found that only 48% of those receiving no treatment ever reached a surgeon or radiation oncologist.LIMITATIONS This was an insured, single-state population. Treatment preferences are unknown.CONCLUSIONS Among all treated patients, whether urban or rural, there was increasing use of radiation and decreasing use of surgery over time. Many patients without treatment never had a consultation with a surgeon/radiation oncologist, and this is an actionable target for improving treatment access for early-stage NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Medicaid , Medicare , População Rural , Estados Unidos/epidemiologia , População UrbanaRESUMO
Background: Patients presenting for emergency department (ED) evaluation may be appropriate for treatment with monoclonal antibodies for mild to moderate COVID-19. While many sites have implemented infusion centers for these agents, EDs will continue to evaluate these patients where appropriate identification and efficient infusion of eligible patients is critical. Objectives: Patients receiving bamlanivimab in the EDs of an academic medical center are described. The primary objective was to describe operational metrics and secondary objectives reported clinical outcomes. Methods: Patients receiving bamlanivimab and discharged from the ED were included from November 16, 2020 to January 16, 2021 in the retrospective, observational cohort. Primary outcome was adherence to institutional criteria. Secondary outcomes included ED visit metrics, clinical characteristics, and return visits within 30 days. Risk factors for return visits were assessed with regression. Results: One hundred nineteen patients were included. Most (71%) were diagnosed with COVID-19 during the ED visit and median symptom duration was 3(IQR 2-5) days. Median number of risk factors for progression to severe disease was 2 (IQR 1-2). Thirty percent had a documented abnormal chest x-ray. Institutional criteria adherence was 99.2%. Median time from ED room to bamlanivimab was 4 (IQR 3.1-5.2) hours. Thirty patients had return visit within 30 days; 19 were COVID-19 related. Two multivariable regression models were analyzed for COVID-19 related return visit. Characteristics on ED presentation were considered in Model I: male gender (OR 3.01[0.97-9.31]), age (per 10 years) (OR 1.49[1.05-2.12]), African-American race (OR 3.46[1.09-11.06]), and symptom duration (per day) (OR 1.34[1.05-1.73]). Model II included labs and imaging acquired in ED. In Model II, age (per 10 years) (OR 1.52[1.07-2.16]) and abnormal CXR (OR 5.74[1.95-16.9]) were associated with COVID-19 related return visits. Conclusions: Administration of bamlanivimab to ED patients can be done efficiently, with the potential to reduce COVID-19 related return visits. Age and abnormal imaging were independent predictors of COVID-19 return visits.
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Doxorubicin (Dox) is a widely used antineoplastic agent that can cause heart failure. Dox cardiotoxicity is closely associated with mitochondrial damage. Mitochondrial fission and mitophagy are quality control mechanisms that normally help maintain a pool of healthy mitochondria. However, unchecked mitochondrial fission and mitophagy may compromise the viability of cardiomyocytes, predisposing them to cell death. Here, we tested this possibility by using Dox-treated H9c2 cardiac myoblast cells expressing either the mitochondria-targeted fluorescent protein MitoDsRed or the novel dual-fluorescent mitophagy reporter mt-Rosella. Dox induced mitochondrial fragmentation as shown by reduced form factor, aspect ratio, and mean mitochondrial size. This effect was abolished by short interference RNA-mediated knockdown of dynamin-related protein 1 (DRP1), a major regulator of fission. Importantly, DRP1 knockdown decreased cell death as indicated by the reduced number of propidium iodide-positive cells and the cleavage of caspase-3 and poly (ADP-ribose) polymerase. Moreover, DRP1-deficient mice were protected from Dox-induced cardiac damage, strongly supporting a role for DRP1-dependent mitochondrial fragmentation in Dox cardiotoxicity. In addition, Dox accelerated mitophagy flux, which was attenuated by DRP1 knockdown, as assessed by the mitophagy reporter mt-Rosella, suggesting the necessity of mitochondrial fragmentation in Dox-induced mitophagy. Knockdown of parkin, a positive regulator of mitophagy, dramatically diminished Dox-induced cell death, whereas overexpression of parkin had the opposite effect. Together, these results suggested that Dox cardiotoxicity was mediated, at least in part, by the increased mitochondrial fragmentation and accelerated mitochondrial degradation by the lysosome. Strategies that limit mitochondrial fission and mitophagy in the physiologic range may help reduce Dox cardiotoxicity.-Catanzaro, M. P., Weiner, A., Kaminaris, A., Li, C., Cai, F., Zhao, F., Kobayashi, S., Kobayashi, T., Huang, Y., Sesaki, H., Liang, Q. Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy.
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Cardiotoxicidade/etiologia , Morte Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Dinâmica Mitocondrial/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Animais , Cardiotoxicidade/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Dinaminas/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. METHODS: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. RESULTS: We identified 153 patients with median follow-up of 4.0 years (range, 0.5-14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54-6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07-3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). CONCLUSIONS: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.
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Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/complicações , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). METHODS: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. RESULTS: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64-9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35-8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). CONCLUSIONS: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.
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Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo-adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). METHODS: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. RESULTS: A total of 160 patients were included. The median follow-up was 47.4 months. The median age at diagnosis was 49.9 years. The 2-year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76-43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03-11.62, P = 0.04), were significant predictors for BM. The 2-year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low-, intermediate-, and high-risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C-index = 0.79). CONCLUSIONS: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies.
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Neoplasias da Mama/secundário , Modelos Biológicos , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
PURPOSE: To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS: A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses. RESULTS: The median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4-12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR) <5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (>20 ng/mL), high AST (>40 IU/L), NLR ≥5, and extrahepatic metastases (P values of <.001, <.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively). CONCLUSIONS: The prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.
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Neoplasias Colorretais/patologia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Centros Médicos Acadêmicos , Aspartato Aminotransferases/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Estados Unidos , Radioisótopos de Ítrio/efeitos adversosRESUMO
In premenopausal women with hormone dependent breast cancers, ovarian suppression is an important part of treatment, and is often achieved with a bilateral salpingo-oophorectomy (BSO). However, this procedure can lead to ovarian remnant syndrome (ORS), a rare condition where the adnexal tissue is not completely removed and can produce estrogen. We describe a case of ORS in a patient with estrogen receptor positive (ER+) breast cancer who had progression of disease after undergoing a BSO, despite optimal therapy. ORS therefore poses a significant treatment challenge in premenopausal ER+ breast cancer patients thought to be rendered menopausal with a BSO.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias Hepáticas/secundário , Ovariectomia/efeitos adversos , Adulto , Anastrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Doenças Ovarianas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2 , SíndromeRESUMO
While surgical management is a common approach for gynecologic malignancies; often disease is locally advanced such that surgery is precluded or surgical pathology reveals disease extent that mandates adjuvant treatment. Gynecologic brachytherapy is an important tool for both definitive and adjuvant treatment of cervical and endometrial cancers. Brachytherapy enables high radiation doses to a target with rapid fall-off to protect adjacent normal structures. This paper aims to detail the usage of brachytherapy in gynecologic cancers with a focus on advances in technique.
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Braquiterapia/instrumentação , Braquiterapia/métodos , Neoplasias dos Genitais Femininos/radioterapia , Feminino , HumanosRESUMO
BACKGROUND AND PURPOSE: Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both efficacy and toxicity. This manuscript characterizes factors associated with intracranial control and radiation necrosis in this group. MATERIALS AND METHODS: All patients had non-small cell lung cancer, renal cell carcinoma, or melanoma and were treated from 2013 to 2021 at two institutions with ICI and SRS/SRT. Univariate and multivariate analysis were used to analyze factors associated with local failure (LF) and grade 2+ (G2 + ) radiation necrosis. RESULTS: There were 179 patients with 549 metastases. The median follow up from SRS/SRT was 14.7 months and the median tumor size was 7 mm (46 tumors ≥ 20 mm). Rates of LF and G2 + radiation necrosis per metastasis were 5.8% (32/549) and 6.9% (38/549), respectively. LF rates for ICI +/- 1 month from time of radiation versus not were 3% (8/264) and 8% (24/285) (p = 0.01), respectively. G2 + radiation necrosis rates for PD-L1 ≥ 50% versus < 50% were 17% (11/65) and 3% (5/203) (p=<0.001), respectively. PD-L1 ≥ 50% remained significantly associated with G2 + radiation necrosis on multivariate analysis (p = 0.03). Rates of intracranial failure were 54% (80/147) and 17% (4/23) (p = 0.001) for those without and with G2 + radiation necrosis, respectively. CONCLUSIONS: PD-L1 expression (≥50%) may be associated with higher rates of G2 + radiation necrosis, and there may be improved intracranial control following the development of radiation necrosis. Administration of ICIs with SRS/SRT is overall safe, and there may be some local control benefit to delivering these concurrently.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Renais , Neoplasias Pulmonares , Lesões por Radiação , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Inibidores de Checkpoint Imunológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Antígeno B7-H1 , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/etiologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Lesões por Radiação/etiologia , Neoplasias Renais/radioterapia , Necrose/etiologia , Estudos RetrospectivosRESUMO
PURPOSE: We hypothesized that concurrent ipilimumab with chemoradiationtherapy (chemoRT) followed by maintenance nivolumab would be safe for patients with unresectable stage III non-small cell lung cancer (NSCLC). We aimed to assess the safety (phase 1) and the 12-month progression-free survival (PFS) (phase 2) in a multi-institution prospective trial. METHODS AND MATERIALS: Eligible patients had unresectable stage III NSCLC. The treatment included platinum doublet chemotherapy with concurrent thoracic radiation therapy to 60 Gy in 30 fractions and ipilimumab (1 mg/kg) delivered during weeks 1 and 4. After chemoRT, maintenance nivolumab (480 mg) was given every 4 weeks for up to 12 cycles. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 5.0. Survival analyses were performed with Kaplan Meier (KM) methods and log-rank tests. RESULTS: The trial was discontinued early after enrolling 19 patients without proceeding to the phase 2 component because of unacceptable toxicity. Sixteen patients (84%) had grade ≥3 (G3+) possible treatment-related toxicity, most commonly pulmonary AEs (n = 8, 42%). Fourteen patients (74%) discontinued study therapy early because of AEs (n = 12, 63%) or patient choice (n = 2, 11%). Eleven patients (58%) experienced G2+ pulmonary toxicity with median time to onset 4.1 months (95% CI 2.6-not reached [NR]), and 12-month freedom from G2+ pulmonary toxicity 37% (95% CI, 16-59). Five patients had G5 AEs, including 3 with G5 pulmonary AEs (1 respiratory failure with pneumonitis and pulmonary embolism, 1 pneumonia/chronic obstructive pulmonary disease exacerbation, 1 pulmonary fibrosis). Despite toxicities, the median PFS was 19.2 months (95% CI 6.1-NR) and the median overall survival was NR (95% CI 6.1-NR) with median follow-up of 30.1 months by the reverse KM method. CONCLUSIONS: Concurrent ipilimumab with chemoRT for unresectable stage III NSCLC is associated with pulmonary toxicity that may limit opportunities for improved outcomes. Future studies aiming to incorporate ipilimumab or other anti-CTLA4 therapies into management of unresectable stage III NSCLC should consider careful measures to minimize toxicity risk.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Humanos , Nivolumabe/efeitos adversos , Ipilimumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Melanoma/patologia , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
PURPOSE: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. METHODS AND MATERIALS: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. RESULTS: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. CONCLUSIONS: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.
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Carcinoma Pulmonar de Células não Pequenas , Doença da Artéria Coronariana , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Doença da Artéria Coronariana/epidemiologia , Cardiopatias/epidemiologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estadiamento de Neoplasias , Estudos Prospectivos , Radioterapia/efeitos adversos , RiscoRESUMO
Human papillomavirus (HPV) causes the majority of oropharyngeal, cervical, and anal cancers, among others. These HPV-associated cancers cause substantial morbidity and mortality despite ongoing vaccination efforts. Aside from the earliest stage tumors, chemoradiation is used to treat most HPV-associated cancers across disease sites. Response rates are variable, and opportunities to improve oncologic control and reduce toxicity remain. HPV malignancies share multiple commonalities in oncogenesis and tumor biology that may inform personalized methods of screening, diagnosis, treatment and surveillance. In this review we discuss the current literature and identify promising molecular targets, prognostic and predictive clinical factors and biomarkers in HPV-associated oropharyngeal, cervical and anal cancer.
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Alphapapillomavirus , Neoplasias do Ânus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Neoplasias do Ânus/terapia , Fatores Biológicos , Feminino , Humanos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/terapia , Papillomaviridae , Infecções por Papillomavirus/complicações , PrognósticoRESUMO
PURPOSE/OBJECTIVES To examine patient characteristics that predispose to higher opioid administration during tandem and ovoid (T&O) high-dose rate (HDR) brachytherapy. METHODS A single-institution retrospective review was performed on patients who underwent brachytherapy for cervical cancer. Patients were included if they received at least one fraction of HDR T&O brachytherapy with analgesia administration recorded in the Medication Administration Record. Fentanyl dose was dichotomized as "low" (mean <125 µg per fraction), or "high" (mean ≥ 125 µg per fraction). Descriptive statistics and multiple logistic regression analysis were performed comparing mean opioid dose per fraction with demographic and clinical information. RESULTS From July 2014 through May 2020, 113 patients underwent 531 T&O HDR brachytherapy fractions with oral benzodiazepine and intravenous opioid fentanyl for conscious sedation. The median opioid dose per fraction was 100 µg fentanyl (range 0-250 µg). Using multiple logistic regression analysis, younger age (OR 1.071, pâ¯=â¯0.002) and higher BMI (OR 1.091, pâ¯=â¯0.019) were associated with increased opioid administration during brachytherapy. Black women received less opioid during brachytherapy when compared to White women (OR 0.296, pâ¯=â¯0.047). FIGO stage, ECOG score, smoking status, prior narcotic use, prior illicit drug use, parity, prior cervical procedure, Smit sleeve placement, and distance to treatment center were not associated with high opioid dose. CONCLUSION Cervical cancer patients who are younger or have higher BMI receive more narcotic analgesia during HDR brachytherapy whereas Black women received less narcotic analgesia, irrespective of age and BMI. This underscores the immediate need to address how pain is assessed and managed during brachytherapy.
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Braquiterapia , Neoplasias do Colo do Útero , Analgésicos Opioides/uso terapêutico , Braquiterapia/métodos , Sedação Consciente , Demografia , Feminino , Humanos , Estudos Retrospectivos , Neoplasias do Colo do Útero/radioterapiaRESUMO
Treatment of advanced non-small cell lung cancer (NSCLC) has markedly changed in the past decade with the integration of biomarker testing, targeted therapies, immunotherapy, and palliative care. These advancements have led to significant improvements in quality of life and overall survival. Despite these improvements, racial and socioeconomic disparities in lung cancer mortality persist. This narrative review aims to assess and synthesize the literature on sociodemographic disparities in the management of advanced NSCLC. A narrative overview of the literature was conducted using PubMed and Scopus and was narrowed to articles published from January 1, 2010, until July 22, 2020. Articles relevant to sociodemographic variation in (I) chemoradiation for stage III NSCLC, (II) molecular biomarker testing, (III) systemic treatment, including chemotherapy, targeted therapy, and immunotherapy, and (IV) palliative and end of life care were included in this review. Twenty-two studies were included. Sociodemographic disparities in the management of advanced NSCLC varied, but recurring findings emerged. Across most treatment domains, Black patients, the uninsured, and patients with Medicaid were less likely to receive recommended lung cancer care. However, some of the literature was limited due to incomplete data to adequately assess appropriateness of care, and several studies were out of date with current practice guidelines. Sociodemographic disparities in the management of advanced lung cancer are evident. Given the rapidly evolving treatment paradigm for advanced NSCLC, updated research is needed. Research on interventions to address disparities in advanced NSCLC is also needed.
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BACKGROUND: The importance of invasive mediastinal nodal staging in early-stage non-small cell lung cancer (NSCLC) in the PET/CT era is dependent on tumor factors that increase risk of nodal metastasis. At our institution, patients undergo biopsy via either CT-guidance (without nodal staging) or navigational bronchoscopy with endobronchial ultrasound transbronchial needle aspiration for nodal staging. This study aims to compare outcomes after stereotactic body radiotherapy (SBRT) stratified by receipt of invasive mediastinal nodal staging. METHODS: In this retrospective study, records of all consecutive patients undergoing SBRT for early-stage NSCLC between 2010 and 2017 were analyzed. The association between time-to event outcomes (recurrence and survival) were evaluated with covariates of interest including tumor size, location, histology, smoking history, prior lung cancer history, radiation dose and receipt of nodal staging. Both univariable and multivariable analyses were used to examine these comparisons. RESULTS: Overall, 158 patients were treated with SBRT. One hundred forty-nine out of one hundred fifty-eight patients (94%) underwent PET/CT staging, and all patients underwent tumor-directed biopsy. Seventy-nine patients underwent navigational bronchoscopy with nodal staging and 79 patients underwent CT-guided biopsy without nodal staging. Receipt of nodal staging was not associated with tumor size (P=0.35), yet was associated with central tumor location (P<0.001). There was no statistically significant association between receipt of nodal staging and time-to-event recurrence or survival outcomes; for example 3-year overall survival (OS) was 65% vs. 67% (P=0.65) and 3-year freedom from nodal failure was 84% vs. 69% (P=0.1) for those with and without nodal staging, respectively. CONCLUSIONS: Similar recurrence and survival outcomes were observed after SBRT regardless of receipt of invasive mediastinal nodal staging. Further prospective evaluation can help identify which patients might derive greatest benefit from invasive staging of the mediastinum in the PET/CT era.
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BACKGROUND: Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models. METHODS: Patients received WBRT to 25-40 Gy in 10-20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0-100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models. RESULTS: Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy-V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69-0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy-V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively. CONCLUSIONS: Xerostomia was most associated with parotid V10Gy-V20Gy, and dry eye with lacrimal V10Gy-V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.
Assuntos
Irradiação Craniana/efeitos adversos , Síndromes do Olho Seco/etiologia , Lesões por Radiação/etiologia , Xerostomia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Síndromes do Olho Seco/diagnóstico , Humanos , Aparelho Lacrimal/efeitos da radiação , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Glândula Parótida/efeitos da radiação , Probabilidade , Estudos Prospectivos , Lesões por Radiação/diagnóstico , Radioterapia Conformacional/efeitos adversos , Medição de Risco , Xerostomia/diagnóstico , Adulto JovemRESUMO
Lung cancer is the leading cause of cancer death worldwide. Diagnosis of early-stage disease is becoming more common. In an aging population, more and more patients have substantial comorbidities that might limit feasibility of surgical management of early-stage disease. Stereotactic body radiotherapy (SBRT) enables delivery of high-dose, precisely delivered radiation to early-stage lung cancers without surgical risk. This technique has rates of local control similar to surgery and can be considered in medically operable patients who refuse surgery. This article details the technique of SBRT, the data for its efficacy, as well as the potential toxicities of treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de NeoplasiasRESUMO
PURPOSE: The size and growth of U.S. radiation oncology (RO) residency positions have important implications for the RO workforce. There are no data on residency growth by geographic region, major urban centers, and program size. We aim to fill this gap. METHODS AND MATERIALS: A database of all RO programs and positions from 2003 to 2018 was created using National Resident Matching Program data. Programs were categorized by U.S. Census Bureau geographic region, major metropolitan location (top 10 combined statistical area vs all other), and program size (small [≤6 trainees], medium [7-12], and large [>12 trainees]). Linear regression with interaction terms was used to determine the effect of region, major metropolitan location, and program size on RO program and position growth over time. RESULTS: There has been a 69% (54-91) and 82% (106-193) increase in the number of RO programs and annual positions from 2003 to 2018. Differences in program and position growth, respectively, were seen in each category. Growth in the Northeast (92% and 83%), South (81% and 113%), and West (125% and 130%) has outpaced the Midwest (17% and 33%). Growth in top 10 metropolitan areas (77% and 92%) is higher than in all other areas (63% and 73%). Growth in medium (68% and 80%) and large (175% and 153%) programs is greater than in smaller (36% and 33%) programs. CONCLUSIONS: There has been a major increase in the number of RO residency programs and positions over the past 15 years. Growth is occurring in every major category but there are differences in magnitude within each category. This information can inform future decisions about RO training programs in the United States.