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1.
Ann Surg Oncol ; 28(13): 9116-9125, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34224045

RESUMO

INTRODUCTION: Early recurrence (ER) is a significant challenge for patients with colorectal peritoneal metastases (CRPM) following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS HIPEC). Preoperative risk stratification for ER would improve preoperative decision making. METHODS: We conducted a retrospective study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Optimal definition of ER was determined via minimum p-value approach based on differentiation of post-recurrence survival. Risk factors for ER were assessed in a derivation cohort by uni- and multivariate logistic regression. A predictive score for ER was generated using preoperative variables and validated in an independent cohort. RESULTS: 384 patients were analyzed, 316 (82%) had documented recurrence. Optimal length of post-operative RFS to distinguish ER (n = 144, 46%) vs. late recurrence (LR) (n = 172, 63%) was 8 mos (p<0.01). ER patients had shorter median OS post-CRS-HIPEC (13.6 vs. 39.4 mos, p<0.01). Preoperative BMI (OR 1.88), liver lesions (OR 1.89), progression on chemotherapy (OR 2.14), positive lymph nodes (OR 2.47) and PCI score (16-20: OR 1.7; >20: OR 4.37) were significant predictors of ER (all p<0.05). Using this model, patients were assigned risk scores from 0 to 9. Intermediate (scores 4-6) and high-risk patients (score 7-9) had observed rates of ER of 56% and 79% and overall 2-year survival rates of 27% and 0% respectively. The model showed fair discrimination (AUC 0.72) and good calibration (Hosmer-Lemeshow GOF p = 0.68). CONCLUSIONS: ER predicts markedly worse OS following surgery. Preoperative factors can accurately stratify risk for ER and identify patients in whom CRS-HIPEC for CPRM is futile.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Futilidade Médica , Recidiva Local de Neoplasia/terapia , Neoplasias Peritoneais/tratamento farmacológico , Estudos Retrospectivos , Taxa de Sobrevida
3.
Ann Surg Oncol ; 28(7): 3522-3531, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33687614

RESUMO

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can offer significant survival advantage for select patients with colorectal peritoneal metastases (CRPM). Low socioeconomic status (SES) is implicated in disparities in access to care. We analyze the impact of SES on postoperative outcomes and survival at a high-volume tertiary CRS HIPEC center. PATIENTS AND METHODS: We conducted a retrospective cohort study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Patients were grouped according to SES. Baseline characteristics, perioperative outcomes, and survival were examined between groups. RESULTS: A total of 226 patients were analyzed, 107 (47%) low-SES and 119 (53%) high-SES patients. High-SES patients were younger (52 vs. 58 years, p = 0.01) and more likely to be White (95.0% vs. 91.6%, p = 0.06) and privately insured (83% vs. 57%, p < 0.001). They traveled significantly further for treatment and had lower burden of comorbidities and frailty (p = 0.01). Low-SES patients more often presented with synchronous peritoneal metastases (48% vs. 35%, p = 0.05). Following CRS HIPEC, low-SES patients had longer length of stay and higher burden of postoperative complications, 90-day readmission, and 30-day mortality. Median overall survival following CRS HIPEC was worse for low-SES patients (17.8 vs. 32.4 months, p = 0.02). This disparity persisted on multivariate survival analysis (low SES: HR = 1.46, p = 0.03). CONCLUSIONS: Despite improving therapies for CRPM, low-SES patients remain at a significant disadvantage. Even patients who overcome barriers to care experience worse short- and long-term outcomes. Improving access and addressing these disparities is crucial to ensure equitable outcomes and improve patient care.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/terapia , Estudos Retrospectivos , Classe Social , Taxa de Sobrevida
4.
Clin Cancer Res ; 27(15): 4195-4204, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33753453

RESUMO

PURPOSE: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma. PATIENTS AND METHODS: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v., 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery. RESULTS: A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5-85.8], with a 43% (95% CI: 27.3-60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively). CONCLUSIONS: Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.See related commentary by Menzies et al., p. 4133.

5.
Ann Surg Oncol ; 28(9): 5287-5296, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33486643

RESUMO

BACKGROUND: Ninety-day hospital readmission rates following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) range from 20 to 40%. OBJECTIVE: The aim of this study was to develop and validate a simple score to predict readmissions following CRS/HIPEC. STUDY DESIGN: Using a prospectively maintained database, we retrospectively reviewed clinicopathologic, perioperative, and day-of-discharge data for patients undergoing CRS/HIPEC for peritoneal surface malignancies between 2010 and 2018. In-hospital mortalities and discharges to hospice were excluded. Multivariate logistic regression was utilized to identify predictors of unplanned readmission, with three-quarters of the sample randomly selected as the derivation cohort and one-quarter as the validation cohort. Using regression coefficient-based scoring methods, we developed a weighted 7-factor, 10-point predictive score for risk of readmission. RESULTS: Overall, 1068 eligible discharges were analyzed; 379 patients were readmitted within 90 days (35.5%). Seven factors were associated with readmission: stoma creation, Peritoneal Cancer Index score ≥ 15, hyponatremia, in-hospital major complication, preoperative chemotherapy, anemia, and discharge to nursing home. In the validation cohort, 25 patients (9.2%) were categorized as high risk for readmission, with a predicted rate of readmission of 69.3% and an observed rate of 76.0%. The score had fair discrimination (area under the curve 0.70) and good calibration (Hosmer-Lemeshow goodness-of-fit p-value of 0.77). CONCLUSION: Our proposed risk score, easily obtainable on day of discharge, distinguishes patients at high risk for readmission over 90 days following CRS/HIPEC. This score has the potential to target high-risk individuals for intensive follow-up and other interventions.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco
6.
J Am Soc Cytopathol ; 9(5): 461-468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32499137

RESUMO

INTRODUCTION: Small biopsies and cytology specimens have become increasingly important for clinical trials and biomarker testing. Thus, institutions must ensure that adequate lesional material meeting the specifications for a multitude of different protocols is available. This can be achieved using rapid on-site evaluation (ROSE). The aim of the present study was to determine the recent clinical trial biopsy characteristics and study the feedback on these collections at our institution. MATERIALS AND METHODS: Clinical trial biopsies performed at our institution and trial feedback (including "queries") were analyzed from the 2017 to 2019. The query data were reviewed in detail, in addition to any protocol modifications related to biopsy requirements and study protocol changes. RESULTS: A total of 698 biopsy collections were performed for clinical trial purposes for 95 trials, with most requiring biopsies at >1 time point (63.2%), for phase I or II trials (92.6%), and for specific tumor types (67.4%). Only 18 of the trials (18.9%) requiring fresh tissue biopsies provided feedback. The feedback included data from 90 cases (12.9%), of which 27 (30.0%) had queries regarding insufficient (n = 10; 37.0%) or borderline (n = 17; 63.0%) tumor tissue. Only 1 (3.7%) of these had had ROSE by cytology. ROSE was performed in accordance with institutional guidelines (45.3%), as required by the study (1.1%), or because of trial modification (5.3%). CONCLUSIONS: The present investigation has shown the high volume of clinical trial biopsies managed at our academic cancer center. Feedback from the trials was low at 18.9% and frequently involved suboptimal cases without ROSE used at acquisition. This has led to more widespread adoption of ROSE to mitigate insufficient biopsy specimens and repeat procedures. The high volume of clinical trial biopsies and variability in trial needs necessitates a collaborative multidisciplinary network, including cytology services, to facilitate these important biopsies for patients with cancer.


Assuntos
Ensaios Clínicos como Assunto/métodos , Feedback Formativo , Neoplasias/diagnóstico , Adulto , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina/métodos , Biópsia com Agulha de Grande Calibre/métodos , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Neoplasias/patologia
8.
Ann Surg Oncol ; 26(8): 2607-2614, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111354

RESUMO

BACKGROUND: Diagnostic terminology and grading of primary appendiceal mucinous neoplasms lacks uniformity. We sought to identify discordance in pathologic reporting by reviewing pathology slides for cases referred to our institution. METHODS: Using guidelines from Peritoneal Surface Oncology Group International (PSOGI) and American Joint Committee on Cancer 8th edition (AJCC8), we compared diagnostic terminology/grading of primary appendiceal mucinous neoplasms (n = 115) between pathology reports from referring institutions and review of slides by pathologists at our high-volume institution. RESULTS: There was discordance in pathologic terminology and grading of primary appendiceal mucinous neoplasms between referring institutions and our institution in 28% and 50% of patients, respectively. In particular, 24% of patients referred with mucinous adenocarcinoma (MACA) had LAMN on our review, and a higher grade MACA was found in 48% of patients referred with low-grade (G1) MACA and 16% of patients referred with high-grade (G2) MACA following our review. Discordance in tumor grade between primary and metastatic disease was seen in 19% of cases based on referred primary tumor grading compared with only 4% following our review. Systemic chemotherapy was unnecessarily administered to four cases of LAMN (6%) and inappropriately not administered to four cases of MACA (6%) before referral due to inaccurate diagnosis/grading by referring institutions. CONCLUSIONS: We found significant discordance in diagnostic terminology/grading of primary appendiceal mucinous neoplasms following review of referred cases. Inaccurate pathologic assessment was associated with overtreatment or undertreatment with chemotherapy. These data highlight the need for pathologic review of such rare cases at high-volume centers.


Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias do Apêndice/patologia , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Variações Dependentes do Observador , Neoplasias Peritoneais/secundário , Terminologia como Assunto , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Neoplasias do Apêndice/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Peritoneais/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
9.
Mod Pathol ; 32(8): 1197-1209, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30962504

RESUMO

DNA was obtained from matching micro-dissected, primary tumor cells, paired metastases, and peripheral blood mononuclear cells (germline) from patients with appendiceal mucinous neoplasms. We compared specimens from patient cohorts comprising low-grade adenomucinous neoplasm versus high-grade mucinous adenocarcinoma using a targeted, amplicon sequencing panel of 409 cancer related genes (Ion Torrent Comprehensive Cancer Panel, Thermo-Fisher, Waltham, MA). Copy number variants, single nucleotide variants and small insertions/deletions were identified using a multiplex algorithm pipeline (GATK, VarScan2, MuTect2, SIFT, SIFT-INDEL, PolyPhen-2, Provean). There were significantly more damaging variants in high-grade versus low-grade tumor cohorts. Both cohorts contained damaging, heterozygous germline variants (catenin ß1; notch receptor 1 and 4) in pathways associated with cell-lineage specification (WNT, NOTCH). Damaging, somatic KRAS proto-oncogene, GTPase mutations were present in both cohorts, while somatic GNAS complex locus mutations were confined to low-grade neoplasms. Variants predominantly affected transcription factors, kinases, and stem cell signaling molecules in canonical pathways including epithelial to mesenchymal transition, stem cell pluripotency, p53, PTEN, and NF-қB signaling pathways. High-grade tumors demonstrated MYC proto-oncogene, bHLH transcription factor (MYC) and death domain associated protein (DAXX) amplification and damaging somatic variants in tumor protein p53 (TP53), likely to amplify an aggressive phenotype. Damaging APC, WNT signaling pathway regulator (APC) deletions were identified in metastatic tissue of both cohorts suggesting a role in invasive disease. Our data suggest that germline dysregulation of WNT and/or NOTCH pathways predisposes patients toward a secretory cell phenotype (i.e., goblet-like cells) upon acquisition of somatic KRAS mutations. Additional somatically acquired variants activating oncogenes MYC and DAXX and inhibiting the critical tumor suppressor, tumor protein TP53, were consistent with manifestation of a high-grade phenotype. These additional changes within the epithelial to mesenchymal transition signaling network (WNT, NOTCH, RAS/ERK/PI3K, PTEN, NF-қB), produce aggressive high-grade tumor characteristics by actively driving cells towards dedifferentiation, proliferation, and migration.


Assuntos
Adenocarcinoma Mucinoso/genética , Neoplasias do Apêndice/genética , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Dosagem de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Polimorfismo de Nucleotídeo Único , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Variações do Número de Cópias de DNA , Diagnóstico Diferencial , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Gradação de Tumores , Fenótipo , Valor Preditivo dos Testes
10.
Ann Surg Oncol ; 26(Suppl 3): 886, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30980195

RESUMO

In the original article, the Comprehensive Complication Index (CCI) was incorrectly identified as the Comprehensive Comorbidity Index. Wherever CCI appears, it refers to the Comprehensive Complication Index.

11.
Ann Surg Oncol ; 26(5): 1445-1453, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30825033

RESUMO

INTRODUCTION: We hypothesized that repeat cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) for peritoneal metastases (PM) may be associated with suboptimal resection, more frequent postoperative complications, and worse oncologic outcomes. METHODS: Using a prospectively maintained database, we compared clinicopathologic, perioperative, and oncologic outcome data in patients undergoing single or repeat CRS-HIPEC procedures. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes. RESULTS: Of the 1294 patients undergoing CRS-HIPEC procedures at our institution, only one CRS-HIPEC procedure (single HIPEC cohort) was performed in 1169 patients (90.3%), whereas 125 patients (9.7%) underwent repeat CRS-HIPEC procedures (repeat HIPEC cohort). Of the 1440 CRS-HIPEC procedures at our institution, a first CRS-HIPEC procedure was performed in 1294 patients (89.9%), whereas subsequent second, third, and fourth CRS-HIPEC procedures were performed in 125 patients (8.7%), 18 patients (1.3%), and 3 patients (0.2%), respectively. Progression-free survival (PFS) following the second CRS-HIPEC procedure was negatively impacted by shorter PFS following the first CRS-HIPEC procedure, independent of other significant variables related to the second procedure, including completeness of cytoreduction and postoperative complications. Patients undergoing multiple CRS-HIPEC procedures were not at higher risk for suboptimal resection or postoperative complications and demonstrated equivalent PFS following each successive procedure compared to the first procedure. CONCLUSIONS: Repeat CRS-HIPEC procedures for PM were not associated with suboptimal perioperative and oncologic outcomes. Our data confirmed our ability to select patients appropriately for repeat CRS-HIPEC procedures.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/mortalidade , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Peritoneais/mortalidade , Reoperação/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
12.
Ann Surg Oncol ; 26(5): 1429-1436, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30623341

RESUMO

BACKGROUND: The aim of this study was to identify factors associated with pleuropulmonary disease recurrence following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for appendiceal pseudomyxoma peritonei (PMP) and to evaluate the oncologic impact of pleuropulmonary disease recurrence compared with isolated peritoneal recurrence. METHODS: From a prospective database, we identified patients who developed pleuropulmonary recurrence, isolated peritoneal recurrence, or no recurrence following CRS/HIPEC for appendiceal PMP. Clinicopathologic, perioperative, and oncologic data associated with the index CRS/HIPEC procedure were reviewed. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with recurrence and survival. RESULTS: Of 382 patients undergoing CRS/HIPEC, 61 (16%) developed pleuropulmonary recurrence. Patients who developed a pleuropulmonary recurrence were more likely to have high-grade (American Joint Committee on Cancer [AJCC] grade 2/3) tumors (74% vs. 56%, p = 0.02) and increased operative blood loss (1651 vs. 1201 ml, p = 0.05) and were more likely to have undergone diaphragm stripping/resection (79% vs. 48%, p < 0.01) compared with patients with an abdominal recurrence. In a multivariate analysis, pleuropulmonary recurrence after CRS/HIPEC was associated with diaphragm stripping/resection, incomplete cytoreduction, and higher AJCC tumor grade. There was a trend towards reduced survival in patients with pleuropulmonary recurrence compared with patients with isolated peritoneal recurrence (median overall survival 45 vs. 53 months, p = 0.87). CONCLUSION: Pleuropulmonary recurrence of appendiceal PMP following CRS/HIPEC is common and may negatively impact survival. Formal protocols for surveillance and therapeutic intervention need to be studied and implemented to improve oncologic outcomes.


Assuntos
Neoplasias do Apêndice/terapia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Hipertermia Induzida/efeitos adversos , Neoplasias Pulmonares/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pleurais/mortalidade , Pseudomixoma Peritoneal/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Apêndice/patologia , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Prognóstico , Estudos Prospectivos , Pseudomixoma Peritoneal/patologia , Estudos Retrospectivos , Taxa de Sobrevida
13.
J Immunother Cancer ; 6(1): 112, 2018 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-30352626

RESUMO

BACKGROUND: Neoadjuvant immunotherapy utilizing novel combinations has the potential to transform the standard of care for locally/regionally advanced melanoma. We hypothesized that neoadjuvant ipilimumab in combination with high dose IFNα2b (HDI) is safe and associated with durable pathologic complete responses (pCR). METHODS: Patients with locally/regionally advanced melanoma were randomized to ipilimumab 3 or 10 mg/kg × 4 doses bracketing definitive surgery, then every 12 weeks × 4. HDI was given concurrently. We evaluated the safety and efficacy of the combination with ipilimumab 3 or 10 mg/kg. The impact on T-cell fraction and clonality were investigated in tumor and blood. RESULTS: Thirty patients (age 37-76), 15 each at 3 and 10 mg/kg, 18 male and 12 female were treated. Considering immune related adverse events (irAEs) of interest, more grade 3/4 irAEs were seen with ipilimumab 10 mg/kg versus 3 mg/kg (p = 0.042). Among 28 evaluable patients, 11 relapsed, of whom 5 died. Median follow-up for 17 patients who have not relapsed was 32 months. The radiologic preoperative response rate was 36% (95% CI, 21-54); 4 patients at ipilimumab 3 mg/kg and 6 at 10 mg/kg and 2 (at 10 mg/kg) later relapsed. The pCR was 32% (95% CI, 18-51); 5 patients at ipilimumab 3 mg/kg and 4 at 10 mg/kg and one (at 3 mg/kg) had a late relapse. In patients with pCR, T-cell fraction was significantly higher when measured in primary melanoma tumors (p = 0.033). Higher tumor T-cell clonality in primary tumor and more so following neoadjuvant therapy was significantly associated with improved relapse free survival. CONCLUSIONS: Neoadjuvant ipilimumab-HDI was relatively safe and exhibited promising tumor response rates with an associated measurable impact on T-cell fraction and clonality. Most pCRs were durable supporting the value of pCR as a primary endpoint in neoadjuvant immunotherapy trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01608594 . Registered 31 May 2012.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Feminino , Humanos , Interferon-alfa/farmacologia , Ipilimumab/farmacologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia
14.
Ann Surg Oncol ; 25(13): 3950-3959, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30302637

RESUMO

BACKGROUND: The authors hypothesized that postoperative complications after cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) have a negative impact on perioperative and oncologic outcomes and that the novel Comprehensive Comorbidity Index (CCI) would be a better predictor of such outcomes than the traditional Clavien-Dindo classification (CDC). METHODS: The study used a prospective database of 1296 patients with peritoneal metastases (PM) undergoing CRS-HIPEC between 2001 and 2016. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes. The Akaike information criterion and the Schwarz (Bayesian information) criterion were used to compare model fitting for CCI versus CDC. RESULTS: In this study, CRS-HIPEC was performed for malignant mesothelioma (12%) and PM from appendix (50%), colorectal (30%), and ovarian (8%) cancers. Major postoperative in-hospital complications (CDC grades 3-4) occurred for 24% of the patients. However, a range of CCI scores was calculated for each CDC grade because 36% of the patients experienced multiple complications. After a median follow-up period of 55 months, the median progression-free survival was 15 months, and the median overall survival was 39 months. In the multivariate Cox proportional hazards models, postoperative in-hospital complications (measured by CDC or CCI) were independent prognostic factors for 30-day post-discharge morbidity and readmission, as well as for survival. The CCI scores demonstrated higher prognostic sensitivity for these outcomes than CDC grades. CONCLUSIONS: Reduction of postoperative complications after CRS-HIPEC is essential for optimal short- and long-term outcomes. For assessing total burden of postoperative complications per patient, CCI is superior to CDC and more sensitive for assessing surgery- and cancer-related outcomes after CRS-HIPEC.


Assuntos
Neoplasias do Apêndice/patologia , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Mesotelioma/terapia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/terapia , Complicações Pós-Operatórias/etiologia , Comorbidade , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Readmissão do Paciente , Neoplasias Peritoneais/secundário , Complicações Pós-Operatórias/classificação , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Taxa de Sobrevida
15.
Ann Surg Oncol ; 25(1): 83-90, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29063296

RESUMO

BACKGROUND: Multifocal intrahepatic cholangiocarcinoma (ICC) has traditionally been treated with surgical resection when amenable. Intra-arterial therapy (IAT) for multifocal ICC has not been directly compared with surgical resection. METHODS: A single-center, retrospective review of consecutive patients treated for multifocal ICC was conducted. Patients with distant metastases or treatment with systemic chemotherapy alone were excluded. Patients were divided into two groups: surgical resection versus IAT; IAT included transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and hepatic arterial infusion (HAI) pump therapy. Subjects were also analyzed by surgical resection, TACE, and HAI pump therapy. RESULTS: Overall, 116 patients with multifocal ICC were studied, 57 in the surgical resection group and 59 in the IAT group (TACE = 41, HAI pump = 16, TARE = 2). The IAT group was characterized by a higher incidence of bilobar disease (88.1% vs. 47.4%, p < 0.001), larger tumors (median 10.6 vs. 7.5 cm, p = 0.004), higher incidence of macrovascular invasion (44.1% vs. 24.6%, p = 0.027), and higher rate of nodal metastases (57.6% vs. 28.6%, p = 0.002). Median overall survival for surgical resection was 20 months versus 16 months for IAT (p = 0.627). Multivariate analysis found that macrovascular invasion [hazard ratio (HR) 2.52, 95% confidence interval (CI) 1.56-4.09] and non-receipt of systemic chemotherapy (HR 3.81, 95% CI 2.23-6.52) were independent poor prognostic risk factors. Surgical resection was not associated with a survival advantage over IAT on multivariate analysis (p = 0.242). CONCLUSION: Despite selection bias for use of surgical resection compared with IAT, no survival advantage was conferred in the treatment of multifocal ICC.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/secundário , Colangiocarcinoma/terapia , Hepatectomia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Ablação por Radiofrequência , Idoso , Antineoplásicos/administração & dosagem , Vasos Sanguíneos/patologia , Quimioembolização Terapêutica , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Radioterapia/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
16.
Ann Surg Oncol ; 25(1): 76-82, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29110275

RESUMO

BACKGROUND: The Peritoneal Surface Oncology Group International (PSOGI) recommends pathologic reporting of tumor cellularity in patients with pseudomyxoma peritonei (PMP) undergoing cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC). We investigated the prognostic significance of PMP cellularity, or lack thereof (acellular mucin), following CRS-HIPEC. METHODS: We reviewed clinical data for 310 CRS-HIPEC procedures in low-grade (American Joint Committee on Cancer grade G1) PMP with acellular mucin (n = 19), scant cellularity (n = 30), or moderate cellularity (n = 242). Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. RESULTS: Compared with patients with acellular mucin, those with scant and moderate cellularity had higher PCI and less-frequent complete macroscopic resection. After an estimated median follow-up of 49 months, 4 patients (14%) with scant cellularity and 127 patients (56%) with moderate cellularity progressed, while none of the patients with acellular mucin progressed. While the median progression-free survival (PFS) was not reached for patients with acellular mucin or scant cellularity (estimated 5-year PFS probability of 100 and 83%, respectively), patients with moderate cellularity demonstrated a median PFS of 32 months (estimated 5-year PFS probability of 27%). In a multivariate model, degree of disease cellularity, or lack thereof (acellular mucin), was an independent predictor of PFS but not overall survival. CONCLUSIONS: Early disease progression is unlikely in patients with acellular mucin undergoing CRS-HIPEC, as opposed to a 14% recurrence rate with scant cellularity. Thorough pathologic assessment for cellularity, or lack thereof (acellular mucin), is vital for accurate prognostication of disease progression for patients with low-grade PMP undergoing CRS-HIPEC.


Assuntos
Neoplasias do Apêndice/patologia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/terapia , Antineoplásicos/administração & dosagem , Antígeno CA-19-9/sangue , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Mucinas , Neoplasias Peritoneais/sangue , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Pseudomixoma Peritoneal/sangue , Estudos Retrospectivos , Taxa de Sobrevida
17.
Am J Surg ; 215(3): 384-387, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29157891

RESUMO

BACKGROUND: Definitive radiotherapy has been suggested as a treatment alternative to surgical resection in Merkel cell carcinoma (MCC). METHODS: Patients with MCC were identified from the National Cancer Database. Propensity score matching accounting for age, Charlson-Deyo score, grade, and AJCC stage was used to match patients in 1:1 fashion by primary treatment (surgery vs. radiotherapy). RESULTS: There were 1227 patients in each group. Median overall survival was improved with surgical resection in stage I/II (76 vs. 25 months, p < 0.001) and stage III disease (30 vs. 15 months, p < 0.001). For stage I/II, 5- and 8-year overall survival were 61% and 42%, in the surgical resection and 32% and 25% in the definitive radiotherapy groups, respectively. For stage III, 5- and 8-year overall survival were 34% and 21% for surgical resection and 19% and 16% in the radiotherapy group, respectively. CONCLUSIONS: Surgical resection for MCC improves median survival compared to definitive radiotherapy while marginally improving long-term survival.


Assuntos
Carcinoma de Célula de Merkel/radioterapia , Carcinoma de Célula de Merkel/cirurgia , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/patologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pontuação de Propensão , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida
18.
Ann Surg Oncol ; 25(2): 550-557, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29181682

RESUMO

BACKGROUND: In the era of modern effective systemic chemotherapy, the comparative effectiveness of hepatic artery infusion (HAI) versus selective internal radiation therapy (yttrium-90 [Y90]) for pretreated patients with isolated unresectable colorectal liver metastasis (IU-CRCLM) remains unknown. This study sought to compare the overall survival (OS) after HAI versus Y90 for IU-CRCLM patients treated with modern chemotherapy and to perform a cost analysis of both regional methods. METHODS: This study retrospectively reviewed patients receiving HAI or Y90 in combination with modern chemotherapy as second-line therapy for IU-CRCLM. Overall survival was calculated from the time of IU-CRCLM diagnosis. Uni- and multivariate models were constructed to identify independent predictors of survival. RESULTS: The inclusion criteria were met by 97 patients (48 HAI patients and 49 Y90 patients). Both groups were similar in terms of age, gender, body mass index (BMI), synchronous disease, carcinoembryonic antigen (CEA), liver tumor burden, and chemotherapy-related characteristics including use of biologics and lines of chemotherapy (all p > 0.05). The HAI group had a better OS than the Y90 group (31.2 vs. 16.3 months; p < 0.001). A trend toward reduced cost favored the HAI group (median, $29,479 vs. $39,092; p = 0.296). The multivariate analysis showed that receipt of HAI (hazard ratio 0.465) and number of chemotherapy lines (HR 0.797) were associated with improved OS from the date of IU-CRCLM diagnosis. CONCLUSIONS: This is the first study to evaluate the comparative effectiveness of HAI versus Y90 in the era of modern chemotherapy, and the findings suggests that HAI is associated with better survival than Y90 for patients with pretreated IU-CRCLM.


Assuntos
Braquiterapia/mortalidade , Neoplasias Colorretais/mortalidade , Floxuridina/administração & dosagem , Artéria Hepática , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Radioisótopos de Ítrio/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Embolização Terapêutica/mortalidade , Feminino , Seguimentos , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Ann Surg Oncol ; 24(13): 3811-3817, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29019111

RESUMO

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) is a complex procedure that often requires ostomy creation to protect high-risk anastomoses. This study aimed to evaluate the authors' institutional experience with CRS-HIPEC-associated ostomies, determine predictors of ostomy creation and reversal, and assess their impact on survival. METHODS: The study analyzed clinicopathologic, perioperative, and oncologic data from a prospective database of 1435 CRS-HIPEC procedures for peritoneal metastases. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with ostomy creation/reversal and survival. RESULTS: Ostomies were created in 34% of the patients, most commonly loop ileostomies (82%). Loop ileostomies were reversed in the majority of patients (83%), whereas non-loop ileostomies were infrequently reversed (< 10% reversal rate). In a multivariate logistic regression model, intermediate or high tumor grade, colectomy/proctectomy, longer operative time, and lower Charlson comorbidity index were associated with loop ileostomy creation, whereas incomplete macroscopic resection, colorectal histology, and major postoperative complications were associated with non-reversal of loop ileostomy. In a multivariate Cox proportional hazards model, intermediate or high tumor grade and non-reversal of loop ileostomy were associated with worse overall survival. CONCLUSIONS: Loop ileostomies were almost always reversed, whereas non-loop ileostomies were almost always permanent. Hospital readmissions for loop ileostomy-related complications were common. Therefore, formal outpatient protocols for prevention and management should be implemented. Non-reversal of loop ileostomy was associated with very poor survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Estomia/métodos , Neoplasias Peritoneais/terapia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Estomas Peritoneais , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Surg Res ; 219: 194-201, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29078882

RESUMO

BACKGROUND: To determine if a select subgroup of patients with combined liver and peritoneal colorectal metastases would derive oncologic benefit from surgical resection as a component of multimodality treatment. MATERIALS AND METHODS: We retrospectively compared 32 patients with combined colorectal peritoneal and liver metastases (CRLM) and 173 patients with peritoneal metastases only (CRPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC). Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting survival. RESULTS: Major postoperative complications (Clavien-Dindo grades 3-5) occurred in 32% (CRLM) and 17% (CRPM) of patients (P = 0.08). After an estimated median follow-up from surgery of 57 mo, propensity score-adjusted median progression-free survival was 5.1 mo (CRLM) and 7.6 mo (CRPM), whereas median overall survival was 13 mo (CRLM) and 21 mo (CRPM). Multivariate Cox-regression analysis of the CRLM group identified number of liver metastases to be the only independent predictor of poor survival (hazard ratio: 2.3, P = 0.03), with a dramatic decrease in survival in patients with more than three liver metastases. CONCLUSIONS: Simultaneous resection of colorectal liver metastases at the time of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion for peritoneal metastases may be associated with worse survival, especially in patients with more than three liver metastases.


Assuntos
Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Neoplasias Peritoneais/cirurgia , Peritônio/cirurgia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Hipertermia Induzida , Fígado/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Peritônio/patologia , Estudos Retrospectivos
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