RESUMO
INTRODUCTION: Up to 90% of patients undergo inadequate resection for incidentally diagnosed T1b-T3 gallbladder cancer (GBC). We evaluated whether adjuvant therapies (ATs) are associated with prolonged overall survival (OS) for patients undergoing inadequate resection of T1b-T3 GBC. METHODS: Patients who underwent inadequate resection, defined as simple cholecystectomy, for T1b-T3, Nx-N2, and M0 GBC were identified from the National Cancer Database (2004-2016). Patient characteristics, variables associated with AT use, and OS were described using the chi-square test, multivariable logistical regression, Kaplan-Meier, and Cox proportional hazard models. RESULTS: Of 1386 patients who met inclusion criteria, most received no AT (64%), 20% received chemotherapy (CT), and 16% received chemoradiotherapy (CRT). Patients who received no AT were generally older (51% ≥ 75 y) and had no comorbidities (65% Charlson Comorbidity Index 0). Among those who received AT, CRT rather than CT, tended to be employed for patients who were older (≥75 y) or had more comorbidities (Charlson Comorbidity Index ≥1). Patients with advanced disease (T3, positive lymph nodes, or positive margins) were more likely to receive CRT. For T1b-T3 GBC, any AT was associated with prolonged median OS compared to no AT (22 months versus 15 mo, P < 0.01). Relative to no AT, CT (hazard ratio 0.76, 95% confidence interval 0.67-0.92) and CRT (0.59, 95% confidence interval 0.49-0.72) were associated with decreased risk of death. CONCLUSIONS: AT was associated with prolonged OS for patients with inadequately resected T1b-T3 GBC. CRT may have a role in treatment for patients with high-risk disease following inadequate resection of T1b-T3 GBC.
RESUMO
Adjuvant systemic therapies effectively reduce the risk of breast cancer recurrence and metastasis, but therapy resistance can develop in some patients due to breast cancer stem cells (BCSCs). Oncolytic adenovirus (OAd) represents a promising therapeutic approach as it can specifically target cancer cells. However, its potential to target BCSCs remains unclear. Here, we evaluated a Cox-2 promoter-controlled, Ad5/3 fiber-modified OAd designed to encode the human sodium iodide symporter (hNIS) in breast cancer models. To confirm the potential of OAds to target BCSCs, we employed BCSC-enriched estrogen receptor-positive (ER+) paclitaxel-resistant (TaxR) cells and tumorsphere assays. OAd-hNIS demonstrated significantly enhanced binding and superior oncolysis in breast cancer cells, including ER+ cells, while exhibiting no activity in normal mammary epithelial cells. We observed improved NIS expression as the result of adenovirus death protein deletion. OAd-hNIS demonstrated efficacy in targeting TaxR BCSCs, exhibiting superior killing and hNIS expression compared to the parental cells. Our vector was capable of inhibiting tumorsphere formation upon early infection and reversing paclitaxel resistance in TaxR cells. Importantly, OAd-hNIS also destroyed already formed tumorspheres seven days after their initiation. Overall, our findings highlight the promise of OAd-hNIS as a potential tool for studying and targeting ER+ breast cancer recurrence and metastasis.
Assuntos
Adenoviridae , Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas , Terapia Viral Oncolítica , Vírus Oncolíticos , Paclitaxel , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/farmacologia , Adenoviridae/genética , Adenoviridae/fisiologia , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologia , Terapia Viral Oncolítica/métodos , Feminino , Linhagem Celular Tumoral , Animais , Camundongos , Simportadores/metabolismo , Simportadores/genética , Vetores Genéticos/genéticaRESUMO
PURPOSE: The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs. METHODS: Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer). RESULTS: We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22). CONCLUSION: Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.
Assuntos
Axila , Neoplasias da Mama , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Pessoa de Meia-Idade , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Excisão de Linfonodo/métodos , Idoso , Biópsia de Linfonodo Sentinela/métodos , Adulto , Metástase Linfática , Mastectomia Segmentar/métodos , Mastectomia/métodos , Estudos RetrospectivosRESUMO
Microwave ablation of liver tumors allows preservation of liver parenchyma with good oncologic outcomes. However, ablation of tumors in the caudate lobe is particularly challenging. Adjacent critical anatomy, particularly the biliary hilum, has led to caudate location being considered a relative contraindication to ablation. To date, no series have described laparoscopic microwave ablation of caudate tumors of the liver. We describe our early experience with laparoscopic microwave ablation of caudate tumors. In this retrospective review of a prospectively maintained single-institution database, six patients with six primary or secondary caudate tumors underwent laparoscopic microwave ablation with no complications. At a median follow-up of 10.5 months, five out of six patients are free of caudate recurrence. Laparoscopic microwave ablation of caudate tumors is feasible. Long-term follow-up is needed to determine if local recurrence risk is higher than in other anatomical segments.
RESUMO
BACKGROUND: American Indian/Alaska Native (AI/AN) breast cancer patients undergo post-mastectomy reconstruction (PMR) infrequently relative to Non-Hispanic White (NHW) patients. Factors associated with low PMR rates among AI/AN are poorly understood. We sought to describe factors associated with this disparity in surgical care. METHODS: A retrospective cohort study of the National Cancer Database (2004 - 2017) identified AI/AN and NHW women, ages 18 - 64, who underwent mastectomy for stage 0 - III breast cancer. Patient characteristics, annual PMR rates, and factors associated with PMR were described with univariable analysis, the Cochran-Armitage test, and multivariable logistical regression. RESULTS: 414,036 NHW and 1,980 AI/AN met inclusion criteria. Relative to NHW, AI/AN had more comorbidities (20% vs 12% Charlson Comorbidity Index ≥ 1, p < 0.001), had non-private insurance (49% vs 20%, p < 0.001), and underwent unilateral mastectomy more frequently (69% vs 61%, p < 0.001). PMR rates increased over the study period, from 13% to 47% for AI/AN and from 29% to 62% for NHW (p <0.001). AI/AN race was independently associated with decreased likelihood of PMR (OR 0.62, 95% CI 0.56-0.69). Among AI/AN, decreased likelihood of PMR was significantly associated with older age at diagnosis, more remote year of diagnosis, advanced disease (tumor size > 5 cm, positive lymph nodes), unilateral mastectomy, non-private insurance, and lower educational attainment in patient's area of residence. CONCLUSION: PMR rates among AI/AN with stage 0 - III breast cancer have increased, yet remain significantly lower than among NHW. Further research should elicit AI/AN perspectives on PMR, and guide early breast cancer detection and treatment.
RESUMO
There have been numerous advances in gene therapy and oncolytic virotherapy in recent years, especially with respect to cutting-edge animal models to test these novel therapeutics. With all of these advances, it is important to understand the biosafety risks of testing these vectors in animals. We performed adenovirus-based viral shedding studies in murine models to ascertain when it is appropriate to downgrade the animals from Biosafety Level (BSL) 2 to BSL 1 for experimental handling and transport. We utilized intravenous injections of a replication-competent adenovirus and analyzed viral shedding via the collection of buccal and dermal swabs from each animal, in addition to obtaining urine and stool samples. The adenovirus hexon copy number was determined by qPCR, and plaque formation was analyzed to assess the biologic activity of viral particles. Our results demonstrate that after 72 h following viral inoculation, there is no significant quantity of biologically active virus shedding from the animals. This observation suggests that on day 4 following adenovirus injection, mice can be safely downgraded to BSL 1 for the remainder of the experiment with no concern for hazardous exposure to laboratory personnel.
Assuntos
Terapia Viral Oncolítica , Vírus Oncolíticos , Camundongos , Animais , Adenoviridae/genética , Eliminação de Partículas Virais , Injeções Intravenosas , Contenção de Riscos Biológicos , Vetores Genéticos , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genéticaRESUMO
BACKGROUND: Patients with estrogen receptor (ER)-positive, HER2-negative breast cancer (BC), and high-risk 21-gene recurrence score (RS) results benefit from chemotherapy. We evaluated chemotherapy refusal and survival in healthy older women with high-RS, ER-positive BC. METHODS: Retrospective review of the National Cancer Database (2010-2017) identified women ≥ 65 years of age, with ER-positive, HER2-negative, high-RS (≥ 26) BC. Patients with Charlson Comorbidity Index ≥ 1, stage III/IV disease, or incomplete data were excluded. Women were compared by chemotherapy receipt or refusal using the Cochrane-Armitage test, multivariable logistical regression modeling, the Kaplan-Meier method, and Cox's proportional hazards modeling. RESULTS: 6827 women met study criteria: 5449 (80%) received chemotherapy and 1378 (20%) refused. Compared to women who received chemotherapy, women who refused were older (71 vs 69 years), were diagnosed more recently (2014-2017, 67% vs 61%), and received radiation less frequently (67% vs 71%) (p ≤ 0.05). Refusal was associated with decreased 5-year OS for women 65-74 (92% vs 95%) and 75-79 (85% vs 92%) (p ≤ 0.05), but not for women ≥ 80 years old (84% vs 91%; p = 0.07). On multivariable analysis, hazard of death increased with refusal overall (HR 1.12, 95% CI 1.04-1.2); but, when stratified by age, was not increased for women ≥ 80 years (HR 1.10, 95% CI 0.80-1.51). CONCLUSIONS: Among healthy women with high-RS, ER-positive BC, chemotherapy refusal was associated with decreased OS for women ages 65-79, but did not impact the OS of women ≥ 80 years old. Genomic testing may have limited utility in this population, warranting prudent shared decision-making and further study.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Receptores de Estrogênio/genética , Receptor ErbB-2/genética , Estimativa de Kaplan-Meier , Quimioterapia Adjuvante , GenômicaAssuntos
Carcinoma de Célula de Merkel , Neoplasias Primárias Desconhecidas , Neoplasias Cutâneas , Humanos , Carcinoma de Célula de Merkel/patologia , Estudos Retrospectivos , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Cutâneas/patologia , Biópsia de Linfonodo Sentinela , Linfonodos/patologia , Excisão de LinfonodoRESUMO
BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Idoso , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Humanos , Medicare , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Estados Unidos , Neoplasias PancreáticasRESUMO
Background: The proportion of women Veterans are increasing and, as such, access to high-quality breast cancer care is important. Prior studies have shown that rural location, age, and a mental health diagnosis negatively impact breast cancer screening rates. Methods: We aimed to retrospectively assess the impact of these risk factors on breast cancer screening adherence rates among Veterans at our institution. Women who were eligible for breast cancer screening per the United States Preventative Services Taskforce guidelines were included. Results: Of 2321 women, overall adherence was 78.2%. There were no significant differences in screening rates between races, various age groups, geographical distribution, and having anxiety or post-traumatic stress disorder (PTSD). However, Veterans with a diagnosis of depression were more likely to adhere to screening guidelines. Having multiple mental health diagnoses was also not a negative risk factor. Conclusions: Our Veteran population's adherence rates are higher than the national average and rural location, race, age, and certain mental health disorders did not negatively affect adherence to screening mammography. Though more research is needed, screening reminders from our women's health coordinator may have improved adherence rates and lowered disparities.
RESUMO
Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002-2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03-1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies.
Assuntos
Melanoma/cirurgia , Doenças da Unha/cirurgia , Neoplasias Cutâneas/cirurgia , Idoso , Feminino , Humanos , Excisão de Linfonodo , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Pessoa de Meia-Idade , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
INTRODUCTION: Esophageal adenocarcinoma (EAC) has increased in incidence in Western countries, and its poor prognosis necessitates the development of novel therapeutics. We previously reported the potential of conditionally replicative adenoviruses (CRAd) as a novel therapeutic treatment for this disease. To further augment the therapeutic effectiveness of our cyclooxygenase-2 (Cox2) controlled CRAd in EAC, we inserted an interferon alpha (IFN) transgene into the viral genome that is expressed upon viral replication. In this manuscript, we analyze the cytotoxic and oncolytic effects of an IFN-expressing oncolytic adenovirus in EAC and the role of the Cox2 promoter in providing for selective replication in human tissues. METHODS: An infectivity-enhanced IFN-expressing CRAd (5/3 Cox2 CRAd ΔE3 ADP IFN) and other control viruses were first tested in vitro with cell lines. For the in vivo study, EAC xenografts in nude mice were treated with a single intratumoral dose of virus. An ex vivo analysis with live tissue slices was conducted using surgically resected EAC patient specimens. RESULTS: Expression of IFN significantly enhanced the cytotoxic and oncolytic effect of a Cox2-promoter controlled CRAd. This virus showed significant tumor growth suppression in a xenograft model. Furthermore, in human EAC samples, the promoter-controlled virus demonstrated selective replication in cancerous tissues, leaving normal esophageal tissue unaffected. CONCLUSION: An IFN-expressing CRAd driven by the Cox2 promoter has strong oncolytic effects as well as cancer-specific replication. Our novel vector possesses critical characteristics that make it a potential candidate for clinical translation to treat EAC.
Assuntos
Adenocarcinoma , Terapia Viral Oncolítica , Adenocarcinoma/terapia , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Humanos , Interferon-alfa , Camundongos , Camundongos NusRESUMO
BACKGROUND: Telemedicine was adopted to minimize exposure risks for patients and staff during the coronavirus disease 2019 pandemic. This study measured patient satisfaction and telemedicine usability in breast cancer care. METHODS: Adult breast cancer patients who had a telemedicine visit at a single academic institution (with surgical, radiation, or medical oncology) from 15 June 2020 to 4 September 2020 were surveyed anonymously. Patient and cancer characteristics were collected, and patient satisfaction and telemedicine usability were assessed using a modified Telehealth Usability Questionnaire with a 7-point Likert scale. Associations of satisfaction and usability with patient characteristics were analyzed using Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS: Of 203 patients who agreed to be contacted, 78 responded, yielding a response rate of 38%. The median age of the respondents was 63 years (range 25-83 years). The majority lived in an urban area (61%), were white (92%), and saw a medical oncologist (62%). The median patient satisfaction score was 5.5 (interquartile range [IQR] 4.25-6.25). The median telemedicine usability score was 5.6 (IQR 4.4-6.2). A strong positive correlation was seen between satisfaction and usability, with a Spearman correlation coefficient (ρ) of 0.80 (p < 0.001). Satisfaction and usability scores did not vary significantly according to patient age, race, location of residence, insurance status, previous visit commute time, oncology specialty seen, prior telemedicine visits, or whether patients were actively receiving cancer treatment. CONCLUSIONS: Breast cancer patients were satisfied with telemedicine and found it usable. Patient satisfaction and telemedicine usability should not limit the use of telemedicine in future post-pandemic breast cancer care.
Assuntos
Neoplasias da Mama , Telemedicina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , COVID-19 , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do PacienteRESUMO
Encoding the sodium iodide symporter (NIS) by an adenovirus (Ad) is a promising strategy to facilitate non-invasive imaging and radiotherapy of pancreatic cancer. However, insufficient levels of NIS expression in tumor cells have limited its clinical translation. To optimize Ad-based radiotherapy and imaging, we investigated the effect of Ad death protein (ADP) deletion on NIS expression. We cloned two sets of oncolytic NIS-expressing Ads that differed only in the presence or absence of ADP. We found that ADP expression negatively affected NIS membrane localization and inhibited radiotracer uptake. ADP deletion significantly improved NIS-based imaging in pancreatic cancer models including patient-derived xenografts, where effective imaging was possible for up to 6 weeks after a single virus injection. This study demonstrates that improved oncolysis may hinder the therapeutic effect of oncolytic viruses designed to express NIS. In vivo studies in combination with 131I showed potential for effective radiotherapy. This also highlights the need for further investigation into optimal timing of 131I administration and suggests that repeated doses of 131I should be considered to improve efficacy in clinical trials. We conclude that ADP deletion is essential for effective NIS-based theranostics in cancer.
RESUMO
Computed tomography (CT) image-guided procedures including biopsy, drug delivery, and ablation are gaining increasing application in medicine. Robotic technology holds the promise for allowing surgeons, and other proceduralists, access to such CT-guided procedures by potentially shortening training, improving accuracy, decreasing needle passes, and reducing radiation exposure. We evaluated surgeon learning and proficiency for image-guided needle placement with an FDA-cleared robotic arm. Five out of six surgeons had no prior CT-guided procedural experience, while one had prior experience with freehand CT-guided needle placement. All surgeons underwent a 60-min training with the MAXIO robot (Perfint Healthcare, Redmond, WA). The robot was used to place needles into three different pre-specified targets on a spine model. Performance time, procedural errors, and needle placement accuracy were recorded. All participants successfully placed needles into the targets using the robotic arm. The average time for needle placement was 3:44 ± 1:43 min. Time for needle placement decreased with subsequent attempts, with average third placement taking 2:29 ± 1:51 min less than the first attempt. The average vector distance from the target was 2.3 ± 1.2 mm. One error resulted in the need for reimaging by CT scan. No errant needle placement occurred. Surgeons (attending fellows and residents) without previous experience and minimal training could successfully place percutaneous needles under CT guidance quickly, accurately, and reproducibly using a robotic arm. This suggests that robotic technology may be used to facilitate surgeon adoption of CT image-guided needle-based procedures in the future.