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A polymorphic variant in the ataxia telangiectasia-mutated (ATM) gene, rs56009889, was recently associated with an increased risk of lung cancer. We studied the role of this variant in the etiology of other cancers. Data from three population-based case-control studies of colon, breast, and lung cancer were used. Participants in these studies (4517 cases, 3383 controls) underwent a genome-wide association study using 500K Illumina OncoArray. The frequency of the AG/AA genotypes differed between Ashkenazi (4.6%) and Sephardi (0.2%) Jews (Pâ <â 0.001). AG/AA frequency was significantly higher in Ashkenazi lung cancer (11.9%) than in controls (2.8%) [adjusted odds ratio (OR)â =â 5.4]. Females had a higher risk than males (ORâ =â 12.8 versus 3.5). The adjusted OR for colorectal cancer was 1.40 [95% confidence interval (CI)â =â 1.01-2.0, Pâ =â 0.045] and for breast cancer was 1.43 (95% CIâ =â 1.01-2.04, Pâ =â 0.046). Never-smokers variant carriers were at higher risk of lung and colon, but not breast, cancer. Cases with the AG/AA genotype had lower mean age at diagnosis, but this difference was significant only for breast cancer (-3.2 years, Pâ =â 0.007). No associations were observed with overall survival. Among the breast cancer subjects, the OR for having triple-negative tumors was 0.45 for AG/AA versus GG genotype (95% CIâ =â 0.2-0.9, Pâ =â 0.02). We confirm the strong association between ATM rs56009889 and lung cancer risk in Ashkenazi Jews and report a mild association with the risk of breast cancer and colorectal cancer.
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CONTEXT AND OBJECTIVES: Cancer centers are increasingly providing complementary medicine as part of an emerging discipline termed 'integrative oncology' (IO). The present study explored factors associated with disparities in referral and adherence to a freely-provided IO program. METHODS: The databases of three oncology centers in northern Israel were searched retrospectively for chemotherapy-treated oncology patients eligible for referral by their oncology healthcare professionals to an integrative physician (IP) consultation. Demographic and cancer-related variables associated with the referral, and attendance by patients at the consultation were identified, as was adherence to the 6-week IO treatment program (high adherence, attending ≥4 IO treatment sessions; low adherence, 0-3 sessions). RESULTS: Of 4988 eligible patients, 1694 (34%) were referred to the IP consultation, with 1331 (78.6%) attending the consultation of which 766 (57.6%) were adherent to IO treatments. Multivariate analysis revealed lower referral rates among patients speaking primarily Arabic and Russian vs. Hebrew (OR = 3.0, 95% CI = 2.0-4.6, P < 0.0001); males vs. females (OR = 1.94, CI = 1.3-2.9, P = 0.001); those not reporting emotional distress (OR = 1.5, CI = 1.02-2.16, P = 0.037); and older age (OR = 1.04, CI = 1.03-1.06, P < 0.0001). Arabic and Russian-speaking patients were less likely to adhere to IO treatments (OR = 0.52, 95% CI = 0.32-0.83, P = 0.006). CONCLUSION: Patients' ethno-national origin and immigration status (primary language, Arabic and Russian), male gender and older age were associated with lower rates of referral to and attendance of the IP consultation, with reduced adherence to weekly IO treatments. These findings require further study to identify barriers toward diversity, equity and inclusion in IO care, increasing awareness among healthcare professionals regarding the benefits of these services for improving patient wellbeing.
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Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Oncologia Integrativa , Neoplasias , Encaminhamento e Consulta , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Israel , Neoplasias/terapia , Estudos Retrospectivos , Idoso , Terapias Complementares , Adulto , Cooperação do PacienteRESUMO
Substantial evidence has accumulated showing that psychological distress affects immune regulation, the response to cancer treatment, and survival. The effect of psychological parameters on the effectiveness of immune checkpoint inhibitor (ICI) treatment has not yet been studied. This preliminary study aimed to (a) examine the associations between psychological factors and responses to ICI treatment and (b) assess the associations between psychological factors and blood measures of sPD-1, sCTLA-4, and cytokines that may alter the effect of ICI treatment. The participants were 62 individuals with advanced cancer, aged 18 years or older, who were candidates for ICI treatment as a new line of treatment. The participants answered questionnaires and provided blood samples and medical data prior to the start of ICI treatment and 3 months after. Perceived health status was positively associated with better responses to ICI treatment. In the subsample of participants with biomarkers, worse health-related quality of life was associated with higher IL-6 and sCTLA-4; emotional distress and sleep difficulties were associated with higher sCTLA-4; and better perceived health was associated with lower IL-6 and TNFα. sPD-1 was not associated with psychological measures. This preliminary study found for the first time that some psychological measures could be linked to responses to cancer treatment, possibly via pro-inflammatory cytokines and sCTLA-4.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Qualidade de Vida , Interleucina-6 , Neoplasias/complicações , ImunoterapiaRESUMO
INTRODUCTION: Microsatellite stable metastatic colorectal cancer (MSS mCRC) is largely refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response. PATIENTS AND METHODS: In this phase I single-institution study, patients with MSS mCRC were treated with a priming dose of s.c vidutolimod, 3 intratumoral injections of vidutolimod and radiosurgery, combined with nivolumab and ipilimumab. Cytokine levels were measured at baseline and at 7 (± 2) weeks. Patients were accrued to 4 consecutive cohorts: (1) Safety run-in without radiosurgery, (2) Radiosurgery prior to intratumoral therapy, (3) Radiosurgery prior to intratumoral therapy with a condensed timeline, and (4) Radiosurgery to extrahepatic lesion following completion of intratumoral therapy. RESULTS: A total of 19 patients were accrued. Median age was 59 years (range 40-71), 68% were male, median number of previous systemic treatments was 3 (range 2-5). None of the patients responded, aside from 1 patient, attributed to high tumor mutational burden. Grade 3 liver toxicity was reported in 0%, 0%, 75%, and 17% in cohorts 1 to 4, respectively. Systemic levels of CXCL10 and IL-10 increased, with a median of 407 versus 78 pg/mL (P = .01), and 66 versus 40 pg/mL (P = .03), respectively. CONCLUSIONS: The combination of intratumoral vidutolimod, radiosurgery, nivolumab and ipilimumab was not found to be efficacious in MSS mCRC with liver metastases. The juxtaposition of liver irradiation and intratumoral vidutolimod injection was associated with high hepatic toxicity.
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Antineoplásicos Imunológicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Radiocirurgia , Neoplasias Retais , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Ipilimumab/uso terapêutico , Ipilimumab/efeitos adversos , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Radiocirurgia/efeitos adversos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Repetições de MicrossatélitesRESUMO
OBJECTIVES: US FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on Food and Drug Administration (FDA) and European Medicines Agency (EMA), clinical data are reviewed independently by the Advisory Committee of Drug Registration (ACDR). In this study, the correlation between the number of discussions at the ACDR and major postapproval variations is examined. DESIGN: This is an observational retrospective comparative cohort study. SETTING: Applications with FDA and/or EMA approval at time of assessment in Israel were included. The timeframe was chosen to allow a minimum of 3 years of postmarketing approval experience for potential major label variations. Data regarding the number of discussions at ACDR were extracted from protocols. Data on postapproval major variations were extracted from the FDA and EMA websites. RESULTS: Between 2014 and 2016, 226 (176 drugs) applications, met the study criteria. 198 (87.6%) and 28 (12.4%) were approved following single and multiple discussions, respectively. A major postapproval variation was recorded in 129 (65.2%) compared with 23 (82.1%) applications approved following single and multiple discussions, respectively (p=0.002). Increased risk for major variation was found for medicines approved following multiple discussions (HR=1.98, 95% CI: 1.26 to 3.09) with a median time of 1.2 years, applications approved based on phase II trials (HR=2.58, 95% CI: 1.72 to 3.87), surrogate endpoints (HR=1.99, 95% CI: 1.44 to 2.74) and oncologic indications (HR=2.48, 95% CI: 1.78 to 3.45). CONCLUSIONS: Multiple ACDR discussions associated with limited supportive data are predictive for major postapproval variations. Moreover, our findings demonstrate that approval by the FDA and/or EMA does not pave the way to automatic approval in Israel. In a substantial per cent of the cases, submission of the same clinical data resulted in different safety and efficacy considerations, requiring additional supporting data in some cases or even rejection of the application in others.
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Aprovação de Drogas , Estados Unidos , Humanos , Preparações Farmacêuticas , United States Food and Drug Administration , Israel , Estudos de Coortes , Estudos RetrospectivosRESUMO
CONTEXT AND OBJECTIVES: The present study examined the perspectives of healthcare providers (HCPs) in designing a multi-disciplinary model of supportive cancer care for the relief of dermatology-related symptoms caused by monoclonal antibody therapies. METHODS: The study employed a mixed research methodology, with qualitative research embedded within a pragmatic prospective study of a registry protocol study. Patients undergoing oncology therapy with MoAB, anti-HER2, and anti-PD-L1 monoclonal antibodies were identified among a cohort of patients referred to an integrative oncology (IO) consultation for symptom relief and improved quality of life (QoL). Case studies with significant dermatology-related concerns were selected and presented to a panel of 6 HCPs trained in medical oncology, oncology nursing, family medicine, supportive cancer care, and IO. HCP narratives were qualitatively analyzed and assessed using ATLAS.Ti software for systematic coding. RESULTS: Of the 924 patients referred to the IO consultation, 208 were treated with monoclonal antibodies, from which 50 were selected for further evaluation. Of these, 7 cases were presented to the HCP team who were asked to identify treatment gaps requiring a multi-disciplinary approach. Qualitative analysis identified 3 major themes: a biophysical perspective; a psycho-social-spiritual perspective; and the implementation of integrated care. DISCUSSION: There is a need for a multi-disciplinary approach when treating patients suffering from monoclonal antibody treatment-related skin toxicities. HCP-reported themes highlight the need to identify patients for whom such an approach is warranted; conditions in which a psycho-social-spiritual perspective should be considered, in addition to a bio-physical approach; and considerations of who should be designated as the patient's primary case manager.
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Terapias Complementares , Neoplasias , Humanos , Qualidade de Vida , Terapias Complementares/métodos , Estudos Prospectivos , Neoplasias/tratamento farmacológico , OncologiaRESUMO
OBJECTIVE: To compare the effectiveness of acupuncture alone or with additional integrative oncology modalities for taxane-induced peripheral neuropathy-related symptoms in patients with gynecological and breast cancer. METHODS: The study was a prospective evaluation of patients undergoing twice-weekly treatments with either acupuncture alone (single-modality, group A) or with additional manual-movement and mind-body therapies (multimodality, group B), for 6 weeks. Symptom severity was assessed at baseline, 6 weeks, and 9 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool; and von Frey perception thresholds. Additional symptoms were also assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Measure Yourself Concerns and Wellbeing (MYCaW) study tool. RESULTS: For the 120 participants (60 in each study arm), baseline to 6-week scores were similar in both groups for improved FACT-Tax physical wellbeing and scores for hand numbness/tingling; EORTC physical functioning and global health status; and MYCaW scores. FACT-Tax taxane subscales and scores for foot numbness/tingling improved only in group A (p=0.038), while emotional wellbeing FACT-Tax (p=0.02) and EORTC pain (p=0.005) improved only in group B. Group B showed greater improvement for FACT-Tax neuropathy-related concerns than group A at 24 hours (p=0.043) and 7 days (p=0.009) after the first treatment. CONCLUSION: Acupuncture alone or with additional integrative oncology modalities may help reduce neuropathy-related symptoms. The single-modality group demonstrated greater improvement for foot numbness/tingling, and the multimodality group demonstrated improvement for pain and improved emotional wellbeing and neuropathy-related concerns in the first week of treatment. TRIAL REGISTRATION NUMBER: NCT03290976.
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Terapia por Acupuntura , Oncologia Integrativa , Doenças do Sistema Nervoso Periférico , Humanos , Qualidade de Vida/psicologia , Hipestesia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Taxoides/efeitos adversos , Dor , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Several studies have investigated whether patients with prior breast cancer (BC) are at an increased risk for endometrial cancer (EC)/uterine serous cancer (USC). We aimed to study this relationship and analyze the effect of prior BC on the incidence and prognosis of USC patients. METHODS: With permission of the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute, clinicopathological information of women diagnosed with BC and following USC were analyzed. The recorded data included age at diagnosis, stage of disease, cause of death, interval time between BC and USC diagnosis, and overall survival. RESULTS: The SEER database included 10,021 patients with USC during the years 1975-2015. 698 (6.96%) of these patients had been previously diagnosed with BC. The incidence of USC in patients with BC history was 57 times higher than in women without BC history (p value <0.001). The incidence of USC did not differ between estrogen receptor (ER)-positive and ER-negative BC patients (p value 0.94). The mean survival of USC patients with previous BC history was 8 years (96 months, 95% CI: 85.7-106.2), shorter than in USC patients with no BC history, presenting a mean survival of 10.6 years (127 months, 95% CI: 124.0-130.8) (p value = 0.002). CONCLUSION: Our results highlight the relationship between BC and USC, suggesting an increased risk for USC among BC patients. This clinical association should be introduced to BC patients, and physicians should be alert to any EC presenting symptom in BC survivors.
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Neoplasias da Mama , Neoplasias Uterinas , Feminino , Humanos , Neoplasias da Mama/epidemiologia , RiscoRESUMO
Breast cancer is a common malignancy and a common cause of cancer-related mortality in women. Pre-treatment workup of breast cancer does not routinely include positron emission tomography scans. We aimed to review cases of women with breast cancer and a synchronous second primary malignancy. We present three cases of women with non-metastatic cancer in whom a synchronous second primary malignancy was found. Synchronous, second primary malignancies which were identified included rectal cancer, gastrointestinal stromal tumor, and non-small cell lung cancer. All second primary malignancies were identified by a PET-CT scan. In conclusion, PET-CT may be used for detection of secondary primary malignancies in select breast cancer patients.
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AIM: To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan. PATIENTS AND METHODS: In this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were pre-therapeutically genotyped for UGT1A1∗28 and UGT1A1∗93. Homozygous variant carriers (UGT1A1 poor metabolisers; PMs) received an initial 30% dose reduction. The primary endpoint was incidence of febrile neutropenia in the first two cycles of treatment. Toxicity in UGT1A1 PMs was compared to a historical cohort of UGT1A1 PMs treated with full dose therapy, and to UGT1A1 non-PMs treated with full dose therapy in the current study. Secondary endpoints were pharmacokinetics, feasibility, and costs. RESULTS: Of the 350 evaluable patients, 31 (8.9%) patients were UGT1A1 PM and received a median 30% dose reduction. The incidence of febrile neutropenia in this group was 6.5% compared to 24% in historical UGT1A1 PMs (P = 0.04) and was comparable to the incidence in UGT1A1 non-PMs treated with full dose therapy. Systemic exposure of SN-38 of reduced dosing in UGT1A1 PMs was still slightly higher compared to a standard-dosed irinotecan patient cohort (difference: +32%). Cost analysis showed that genotype-guided dosing was cost-saving with a cost reduction of 183 per patient. CONCLUSION: UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving. Therefore, UGT1A1 genotype-guided dosing of irinotecan should be considered standard of care in order to improve individual patient safety.
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Neutropenia Febril , Glucuronosiltransferase , Camptotecina/efeitos adversos , Custos e Análise de Custo , Genótipo , Glucuronosiltransferase/genética , Humanos , Irinotecano/efeitos adversos , Estudos ProspectivosRESUMO
INTRODUCTION: Breast cancer and thyroid malignancy are very common tumors in women. These tumors have high curative rates, therefore, a significant probability of both exists during a life-span. Epidemiological studies support the presence of some common risk factors. These data raise questions about biological mechanisms and changes at the molecular level of breast and thyroid cancer cells that may be a target for biological therapy in a common pathway. Here, we present a clinical case of a patient who had metastatic breast cancer and at the time of diagnosis another primary malignant tumor was revealed in the thyroid gland. The issue of treatment choice during two simultaneous active malignancies is always a challenging theme. Surprisingly, both tumors responded to a treatment protocol tailored to a single one. The treatment chosen was not chemotherapy but a special biological treatment combined with hormonal therapy. Further to the case presentation, we discuss molecular changes appearing in both tumors, malignant cell activity mechanisms accordingly, and a basis for biological treatment that may affect two processes simultaneously.
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Neoplasias da Mama , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
BACKGROUND: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures. OBJECTIVES: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care. METHODS: A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic. RESULTS: In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment. CONCLUSIONS: Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.
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COVID-19/prevenção & controle , Hospitais/estatística & dados numéricos , Neoplasias/terapia , Equipamento de Proteção Individual/provisão & distribuição , Pesquisas sobre Atenção à Saúde , Humanos , Israel , Triagem/métodosAssuntos
Adenina/análogos & derivados , Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Piperidinas/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Receptores ErbB/genética , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
CONTEXT AND OBJECTIVES: The present study examined the impact of an integrative oncology treatment program in the relief of pain in patients undergoing chemotherapy and/or palliative care. METHODS: In this pragmatic prospective controlled study, patients undergoing chemotherapy and/or palliative care were referred by their oncology healthcare providers to an integrative physician (IP) consultation, followed by weekly integrative treatments. Patients attending ≥ 4 sessions during the first 6 weeks of the study were considered to be highly adherent to integrative care (AIC). Pain was assessed at baseline and at 6 and 12 weeks using the ESAS (Edmonton Symptom Assessment Scale) and EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) tools. RESULTS: Of 815 eligible patients, 484 (59.4%) were high-AIC and 331 low-AIC. Mean pain scores decreased significantly from baseline to 6 and 12 weeks in both groups. However, ESAS and EORTC pain scores improved significantly more in the high-AIC group at 6 weeks (p= 0.008), though not at 12 weeks. Between-group analysis of participants undergoing adjuvant/neo-adjuvant chemotherapy showed higher pain reduction in the high-AIC group at 6 weeks (ESAS, p = 0.006; EORTC, p = 0.046), as was the case with patients receiving palliative care (ESAS p = 0.04; EORTC p = 0.056). CONCLUSIONS: High adherence to integrative care was found to be associated with a greater effect on pain relief at 6 weeks but not at 12 weeks in patients undergoing chemotherapy and/or palliative care.
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Dor do Câncer/terapia , Oncologia Integrativa/métodos , Neoplasias/terapia , Cuidados Paliativos/métodos , Medicina de Precisão/métodos , Adulto , Idoso , Dor do Câncer/diagnóstico , Dor do Câncer/epidemiologia , Terapias Complementares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Manejo da Dor/métodos , Medição da Dor , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Oncological treatments of older patients have many unresolved questions mainly because of the fact that these patients were not eligible to be included in most clinical trials. The aim of this study was to evaluate the treatment approach to localized rectal cancer in the older population, including complication rates and overall survival in patients treated with curative intent. MATERIALS AND METHODS: A retrospective review of patients older than 80 years old (group A) who were treated for clinical stages II to III rectal cancer. The data collection included demographics, comorbidities, treatment protocols, adverse events, time of death, and a comparison with a group of patients aged 65 to 75 years (group B). RESULTS: A total of 88 patients were included in the analysis (group A, 35; group B, 53). The groups were balanced with regards to sex, comorbidities, pretreatment albumin, and hemoglobin levels (for all categories P>0.05). More patients in group A (25%) received preoperative treatment as in-patients (P=0.022) and were treated with radiation only (P<0.0001) as the initial treatment approach. In group A, in 82% of patients the initial chemotherapy dose was reduced to 75% or less of the calculated dose compared with 7% in group B (P<0.001). Discontinuation of chemotherapy was needed in 55% in group A and 31% in group B (P=0.07). Median overall survival was 33 months in group A and 55 months in group B (P=0.06), 5-year overall survival was 27% and 60%, respectively (P=0.004). CONCLUSIONS: The age has a significant implication on preoperative treatment, chemotherapy dose, hospitalization rates, and survival.
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Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Feminino , Fluoruracila/administração & dosagem , Hospitalização , Humanos , Masculino , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Dosagem Radioterapêutica , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
AIM: Immune-related toxicities of immune checkpoint inhibitors (CPIs) require prompt diagnosis and treatment. Atherosclerosis has an inflammatory component; we speculated this inflammation could be enhanced by CPIs. We aimed to evaluate the risk of acute vascular events (AVEs) on CPIs. METHODS: Patients treated by CPIs in Sheba Medical Center (Israel) between January 2015 and May 2018 were retrospectively identified from electronic medical records. AVEs were identified and verified by chart review. Age, sex, diabetes, hypertension, smoking, dyslipidemia, previous AVE, renal failure, cancer type and specific treatments were evaluated as potential risk factors. AVE rate on CPIs was compared with that on chemotherapy or on combined chemo-immunotherapy in patients with lung adenocarcinoma. Survival of patients with AVEs was compared with that of patients without AVEs. RESULTS: CPI was administered to 1215 patients. AVEs within six months after CPI initiation occurred in 2.6% (95% confidence interval [CI]: 1.8-3.6) of patients, more common than in later time periods. In lung adenocarcinoma, event rate was 5.2% (95% CI: 2.8-9.2). Lung adenocarcinoma, prior AVE, hypertension and dyslipidemia were correlated with AVEs. AVE rate in patients with non-small cell lung cancer adenocarcinoma was similar whether on chemotherapy or on CPI. Survival of patients with AVEs was worse than that of those without AVEs. CONCLUSION: The similarly increased rates of AVEs for patients on CPI, on chemotherapy or on both suggest that although CPI may not augment the risk of AVE over that of chemotherapy, it carries a similar and significant risk of such adverse event. Caution should be exercised for patients with risk factors for AVEs.
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Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Imunoterapia/mortalidade , Neoplasias/tratamento farmacológico , Doenças Vasculares/induzido quimicamente , Doença Aguda , Idoso , Feminino , Seguimentos , Humanos , Masculino , Neoplasias/imunologia , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Doenças Vasculares/patologiaRESUMO
BACKGROUND: Anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided tumors. The Oncotype Recurrence Score (RS) assay is a clinically validated predictor of recurrence risk in patients with stage II colorectal cancer (CRC). Previous studies had indicated that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors are associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors. We aimed to evaluate whether these two validated prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC. MATERIALS AND METHODS: We retrospectively analyzed patients with T3 mismatch repair-proficient (MMR-P) stage II CRC for whom RS assay was performed. Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. RS and CDX2 expression were correlated with primary tumor location. RESULTS: The analysis included 1,147 patients with MMR-P stage II CRC (median age 69 years [range 29-93]). Tumor distribution across the colon was as follows: 46% (n = 551) were right-sided and 54% (n = 596) were left-sided. RS was higher in right-sided tumors (p = .01). The RS results gradually decreased across the colon (cecum, highest score; sigmoid, lowest score; p = .04). Right-sided tumors exhibited more CDX2-negative tumors (p = .07). CONCLUSION: Our study indicates that right-sided colorectal tumors may display worse prognosis compared with left-sided tumors in MMR-P stage II CRC. Primary tumor location may serve as a prognostic factor that should be taken into account for recurrence risk assessment and consideration of adjuvant treatment. IMPLICATIONS FOR PRACTICE: Sidedness matters, even in stage II colorectal cancer (CRC). Using two previously established prognostic tools, the Oncotype DX assay and CDX2 expression, this study found that right-sided tumors may display worse prognosis compared with left-sided tumors in mismatch repair-proficient stage II CRC. Therefore, primary tumor location should be taken into account for recurrence risk assessment and consideration of adjuvant treatment.
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Biomarcadores Tumorais/metabolismo , Fator de Transcrição CDX2/metabolismo , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Estudos RetrospectivosRESUMO
We report a 48-year-old woman with metastatic infiltrating lobular carcinoma of the breast. Though her metastatic disease remained stable, she was repeatedly admitted for symptomatic anaemia and treated by red blood cell and platelet transfusions with increasing frequency as time elapsed. Abdominal examination and ultrasound revealed splenomegaly (27 cm span). A bone marrow biopsy showed fibrosis and foci of metastatic carcinoma. Splenectomy ameliorated her transfusion-dependent anaemia and thrombocytopaenia. Histopathology revealed multiple foci of metastatic carcinoma and scattered foci of extramedullary haematopoiesis. Differential diagnosis of anaemia and thrombocytopaenia in patients with cancer include bone morrow involvement by cancer cells, iron-deficiency anaemia, microangiopathies and chemotherapy suppression of haematopoiesis. Splenic involvement with cancer is common in patients with multivisceral disease. Many may regard transfusion-dependent severe anaemia and thrombocytopaenia as an end-stage disease in these patients. Nevertheless, palliative splenectomy should be considered in patients with possible hypersplenism who will otherwise survive for a relatively prolonged period of time.
Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Neoplasias Esplênicas/diagnóstico , Anemia/etiologia , Neoplasias da Mama/patologia , Carcinoma Lobular/complicações , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esplenectomia , Neoplasias Esplênicas/complicações , Neoplasias Esplênicas/secundário , Neoplasias Esplênicas/cirurgia , Esplenomegalia/diagnóstico por imagem , Trombocitopenia/etiologiaRESUMO
BACKGROUND: Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care. OBJECTIVE: To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel. PATIENTS AND METHODS: This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. RESULTS: The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1-4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12-1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected. CONCLUSIONS: Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.