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BACKGROUND: Preoperative partial breast irradiation (PBI) can increase accuracy of target volume definition and decrease irradiated volumes compared with postoperative PBI. In the ABLATIVE trial (NCT02316561), 15/36 patients achieved pathologic complete response (pCR) 6-8 months after preoperative PBI and breast conserving surgery (BCS). We now present the 5-year results. METHODS: The ABLATIVE trial is a Dutch prospective cohort study in four hospitals. Women aged ≥ 50 years with unifocal, non-lobular breast cancer, ER-positive, HER2-negative, and a tumor negative sentinel node were treated between 2015-2018 with preoperative single-dose PBI followed by BCS after six or eight months. The primary endpoint was pCR. Secondary endpoints were yearly evaluated oncological outcomes, toxicity, cosmetic outcome (assessed by patients and physicians) and quality of life. RESULTS: Thirty-six patients were treated with BCS six (n=15) and eight (n=21) months following PBI. Median tumor size was 13 mm (IQR 9-16). After a median follow-up of 5.5 years (IQR 5.1-6.0 years), two (6%) patients had ipsilateral breast events and two (6%) distant metastases. The 5-years overall survival was 94% [95% CI 87-100%]. The 5-year cumulative incidence of clinician-reported grade 1/2 breast fibrosis and breast discomfort/pain were 94%/6% and 75%/6%, respectively. The proportion of patients (very) satisfied with the cosmetic results was 89% at baseline and 78% at 5 years. Cosmetic results evaluated using the BCCT.core software were excellent or good in all patients. The 4-year median global quality of life score was 83 (IQR 67-92), similar to baseline (83 (IQR 75-83), p=0.42). CONCLUSION: Preoperative single-dose PBI and BCS may be an oncologically safe treatment with mild late toxicity, and no decline in cosmetic results and quality of life during 5 years of follow-up. This means that preoperative instead of standard postoperative irradiation has the potential to challenge the current clinical practice.
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INTRODUCTION: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18-65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. METHODS: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. RESULTS: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. CONCLUSIONS: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.
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Patients with pathological nipple discharge (PND) often undergo local surgical procedures because standard radiologic imaging fails to identify the underlying cause. MicroRNA (MiRNA) expression analysis of nipple fluid holds potential for distinguishing between breast diseases. This study aimed to compare miRNA expression levels between nipple fluids from patients with PND to identify possible relevant miRNAs that could differentiate between intraductal papillomas and no abnormalities in the breast tissue. Nipple fluid samples from patients with PND without radiological and pathological suspicion for malignancy who underwent a ductoscopy procedure were analyzed. We used univariate and multivariate regression analyses to identify nipple fluid miRNAs differing between pathologically confirmed papillomas and breast tissue without abnormalities. A total of 27 nipple fluid samples from patients with PND were included for miRNA expression analysis. Out of the 22 miRNAs examined, only miR-145-5p was significantly differentially expressed (upregulated) in nipple fluid from patients with an intraductal papilloma compared to patients showing no breast abnormalities (OR 4.76, p = 0.046), with a diagnostic accuracy of 92%. miR-145-5p expression in nipple fluid differs for intraductal papillomas and breast tissue without abnormalities and, therefore, has potential as a diagnostic marker to signal presence of papillomas in PND patients. However, further refinement and validation in clinical trials are necessary to establish its clinical applicability.
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Enfermedades de la Mama , Neoplasias de la Mama , MicroARNs , Secreción del Pezón , Papiloma Intraductal , Papiloma , Humanos , Femenino , Papiloma Intraductal/diagnóstico , Papiloma Intraductal/genética , Papiloma Intraductal/patología , Endoscopía/métodos , Secreción del Pezón/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Enfermedades de la Mama/metabolismo , Pezones/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Papiloma/diagnóstico , Papiloma/genética , Papiloma/metabolismoRESUMEN
Background: Most patients suffering from pathological nipple discharge (PND) undergo local surgical procedures because standard radiological imaging often fails to reveal the cause. Ductoscopy is a minimally invasive endoscopic technique that enables direct intraductal visualization and can avoid unnecessary diagnostic surgical procedures. Hence, patients with recurrent or persistent PND after an unsuccessful ductoscopy procedure still undergo unnecessary surgery. This study describes the experience of a second ductoscopy procedure in patients with recurrent or persistent PND without suspicious radiological findings. Methods: Patients with recurrent or persistent PND who underwent two ductoscopy procedures between 2010 and 2017 were retrospectively analyzed. The second ductoscopy was performed when the first ductoscopic attempt was unsuccessful due to technical problems. The primary outcome was the number of preventable surgical procedures. Results: A total of 17 patients underwent two ductoscopy procedures. The first ductoscopy showed a polypoid lesion in 10 patients (58.8%), no abnormalities in 3 patients (17.6%), and in 4 patients (23.5%), it was not possible to visualize the ductal tree. Post-procedure, all patients suffered from PND. After two ductoscopic attempts, PND stopped in 10 patients (58.8%), and 7 patients (41.2%) still suffered from PND and were operated on. Pathology of the resection specimens showed no abnormalities in 1 patient, a papilloma in 5 patients, and ductal carcinoma in situ in 1 patient. Conclusion: A second ductoscopy procedure can be considered in the diagnostic work-up of patients suffering from persistent or recurrent PND after an unsuccessful first ductoscopic attempt to avoid unnecessary surgery in about 59% of the cases.
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PURPOSE: Breast cancer patients face complex decisions about immediate breast reconstruction (BR) after mastectomy. We evaluated the efficacy of an online decision aid in improving the decision-making process, decision quality and health outcomes in breast cancer patients considering immediate BR. METHODS: In a multicenter randomized controlled trial, patients were allocated to either the intervention group receiving care-as-usual (CAU) with access to an online decision aid, or the control group receiving CAU with an information leaflet. The primary outcome was decisional conflict. Secondary outcomes assessed the process of decision making (e.g. preparation for decision making, satisfaction with information), decision quality (decision regret, knowledge) and health outcomes (e.g. satisfaction with BR outcomes, body image). Patients completed questionnaires at baseline (T0), 1 week after consultation with a plastic surgeon (T1), 3 months (T2), and 12 months post-surgery (T3). RESULTS: We included 250 patients. Decisional conflict decreased over time in both groups, with no between group differences. Intervention participants felt better prepared for decision making than controls (P = .002). At T2, 87% of intervention participants were (very) satisfied with the information about BR, compared to 73% of control participants (P = .011). No significant between group differences were observed in any other outcome. CONCLUSION: Our online decision aid was as effective in reducing decisional conflict as an information leaflet about immediate BR after mastectomy. However, the decision aid substantially improved the decision-making process by better preparing breast cancer patients for decisions about immediate BR.
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BACKGROUND: Oncoplastic reconstructive surgery as an extension of breast-conserving surgery leads to better aesthetic results, an increase in tumor-free margins, and a reduction of re-excision rates. However, oncologic resection is often more extensive than expected, sometimes resulting in the plastic surgeon deviating from the predetermined plan. For optimal planning of the reconstruction, it is mandatory to estimate volume defects after lumpectomy as accurately as possible. This study aims to find preoperative predictors of lumpectomy resection size. METHODS: All consecutive patients diagnosed with invasive breast carcinoma or carcinoma in situ and treated primarily with breast-conserving surgery between 2018 and 2020 at the University Medical Center Utrecht and Alexander Monro Hospital were included. Variables measured were patient characteristics and tumor characteristics. Data was analyzed in a multiple linear regression analysis. RESULTS: A total of 423 cases (410 patients) were included, with a median age of 58 (range 32-84) and a mean BMI of 25.0 (SD=9.3). The mean maximum radiological tumor diameter was 18.0 mm (SD=13.2), and the mean maximum lumpectomy diameter was 58.8 mm (SD=19.2). Multiple linear regression analysis found an explained variance of R 2 = 0.60 (p = < .00), corrected for operating surgeon. Significant predictors for postoperative lumpectomy size were BMI, breast size, and maximum preoperative radiological tumor diameter. Moreover, a predictive tool for lumpectomy size was developed and a web-based application was created on www.evidencio.com under the title ''Predicted lumpectomy size'', to facilitate the use of our tool in a clinical setting. CONCLUSION: Postoperative lumpectomy size can be predicted with BMI, breast size and radiological tumor size. This model could be beneficial for (plastic) breast surgeons in planning reconstructions and to prepare and inform their patients more accurately.
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BACKGROUND: The role of duct excision surgery is not clearly defined in patients with pathological nipple discharge without other clinical and radiological abnormalities. The primary aim of this systematic review was to determine the malignancy rate in patients with pathological nipple discharge after duct excision surgery (microdochectomy/major duct excision). The secondary aims were to determine the recurrence rate of pathological nipple discharge after surgery and to assess breast cancer development after surgery. METHODS: MEDLINE and Embase were searched from inception to March 2023, using search terms related to 'nipple discharge', 'nipple fluid', 'microdochectomy', 'duct excision', and 'minimally invasive surgical procedure'. Studies reporting data about women who underwent duct excision surgery for pathological nipple discharge without clinical and radiological suspicion of breast cancer, as well as reporting data on women diagnosed with breast cancer after duct excision surgery, were included. RESULTS: A total of 318 titles were identified, of which nine publications were included in the analysis. This resulted in 1108 patients with pathological nipple discharge who underwent a duct excision. The weighted mean rate of malignancy after duct excision surgery was 8.1 per cent (ranging from 2.3 to 13.5 per cent). Three studies described the recurrence rate of pathological nipple discharge (ranging from 0 to 12 per cent) and two studies reported breast cancer development in the follow-up in a total of three patients (less than 1 per cent). CONCLUSION: The malignancy rate after duct excision surgery for pathological nipple discharge was low in patients with pathological nipple discharge without radiological and clinical abnormalities and approximately 9 of 10 patients undergo surgery for a benign cause. Improvement of the diagnostic and therapeutic workup is needed to prevent patients from undergoing (unnecessary) exploratory surgery.
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Neoplasias de la Mama , Pezones , Humanos , Femenino , Pezones/cirugía , Neoplasias de la Mama/patología , Procedimientos Quirúrgicos Mínimamente Invasivos , Radiografía , Mastectomía SegmentariaRESUMEN
WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article describing the development of risk calculators for use in people who develop a type of melanoma on their skin called "thin" melanoma to predict the likelihood that their cancer will return. The article was originally published in the Journal of Clinical Oncology in 2021. HOW WERE THE CALCULATORS DEVELOPED?: Calculations were performed to predict the chance of people with thin melanomas surviving without their melanoma recurring. Three graphical prediction calculators (called nomograms) were developed, along with easy-to-use online calculators using the same underlying calculation methods. The model was developed using data for 25,930 Dutch people diagnosed with thin melanomas (called the "development set"). To test its ability to predict melanoma recurrence, it was then compared with data for 2,968 Australian people with melanoma (the "validation set"). The calculators developed in the Dutch patients were found to accurately predict the risk of melanoma recurring for people with melanoma in the Australian "validation" group. WHAT DO THE RESULTS MEAN?: The calculators provide estimates of the risk of the melanoma returning for people with thin melanomas. The easy-to-use online calculators are freely available on a smartphone, tablet or computer, and will assist in providing accurate estimates of recurrence risks for individuals with thin melanomas, allowing more intensive follow-up of those whose predicted risk of their melanoma returning is high.
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Melanoma , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Nomogramas , Australia , Melanoma/diagnóstico , Melanoma/epidemiología , PielRESUMEN
BACKGROUND: Melanomas in the first 2 decades of life are uncommon and poorly understood. OBJECTIVE: To assess clinicopathologic features and survival of children (≤11 years) and adolescents (12-19 years) diagnosed with melanoma. METHODS: A pooled cohort of 514 patients was analyzed (397 Dutch, 117 Australian; 62 children, 452 adolescents). Pathology reports were reevaluated to determine melanoma subtypes. Multivariable Cox models were generated for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Melanoma subtypes were conventional melanoma (superficial spreading, nodular, desmoplastic, and acral lentiginous), spitzoid melanoma, and melanoma associated with a congenital nevus in 428, 78, and 8 patients, respectively. Ten-year RFS was 91.5% (95% confidence interval [CI], 82.4%-100%) in children and 86.4% (95% CI, 82.7%-90.3%) in adolescents (P = .32). Ten-year OS was 100% in children and 92.7% (95% CI, 89.8%-95.8%) in adolescents (P = .09). On multivariable analysis possible only for the adolescent cohort due to the small number of children, ulceration status, and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status and melanoma subtype were not. Breslow thickness >4 mm was associated with worse RFS. LIMITATIONS: Retrospective study. CONCLUSIONS: Survival rates for children and adolescents with melanomas were high. Ulceration, head or neck location and Breslow thickness >4 mm predicted worse survival in adolescents.
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Melanoma , Neoplasias Cutáneas , Humanos , Adolescente , Niño , Estudios Retrospectivos , Pronóstico , Australia , Melanoma/patología , Neoplasias Cutáneas/patología , Biopsia del Ganglio Linfático Centinela , Tasa de SupervivenciaRESUMEN
The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Proteoma/metabolismo , Estudios Prospectivos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Proteínas Sanguíneas/análisis , Biomarcadores , Biomarcadores de TumorRESUMEN
Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg-1 and nivolumab 3 mg kg-1. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3-4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab.
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Melanoma , Neoplasias Cutáneas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Ipilimumab , Melanoma/tratamiento farmacológico , Melanoma/patología , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Nivolumab , Calidad de Vida , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Pseudomyxoma peritonei (PMP) is an uncommon clinical condition characterized by the presence of mucinous ascites, mainly induced by perforated appendiceal mucinous neoplasms (AMN). The peritoneal surface of the small bowel is usually spared from disease manifestation due to peristaltic movements. Mucinous tumours can disseminate as PMP on the entire peritoneum, but are rarely intraluminal. For the first time in literature, we report a case of intraluminal PMP involving the ileum. CASE PRESENTATION: A 75-year-old male was treated for perforated AMN and disseminated PMP with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. During follow-up, the patient developed intraperitoneal recurrence together with intraluminal depositions in the ileum, both disease manifestations with identical KRAS and SMAD4 mutations. Hereafter, the patient was treated with palliative care. CONCLUSION: This case illustrates the variation in the biological and clinical behaviour of this rare disease. Clinicians should be aware of unusual tumour distribution patterns of PMP, including the presence of mucinous tumour within the small bowel.
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Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Seudomixoma Peritoneal , Anciano , Neoplasias del Apéndice/patología , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Humanos , Hipertermia Inducida/efectos adversos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Neoplasias Peritoneales/patología , Seudomixoma Peritoneal/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: In colorectal cancer (CRC), the consensus molecular subtype 4 (CMS4) is associated with therapy resistance and poor prognosis. Clinical diagnosis of CMS4 is hampered by locoregional and temporal variables influencing CMS classification. Diagnostic tools that comprehensively detect CMS4 are therefore urgently needed. METHODS: To identify targets for molecular CMS4 imaging, RNA sequencing data of 3232 primary CRC patients were explored. Heterogeneity of marker expression in relation to CMS4 status was assessed by analysing 3-5 tumour regions and 91.103 single-tumour cells (7 and 29 tumours, respectively). Candidate marker expression was validated in CMS4 peritoneal metastases (PM; n = 59). Molecular imaging was performed using the 68Ga-DOTA-FAPI-46 PET tracer. RESULTS: Fibroblast activation protein (FAP) mRNA identified CMS4 with very high sensitivity and specificity (AUROC > 0.91), and was associated with significantly shorter relapse-free survival (P = 0.0038). Heterogeneous expression of FAP among and within tumour lesions correlated with CMS4 heterogeneity (AUROC = 1.00). FAP expression was homogeneously high in PM, a near-homogeneous CMS4 entity. FAPI-PET identified focal and diffuse PM that were missed using conventional imaging. Extra-peritoneal metastases displayed extensive heterogeneity of tracer uptake. CONCLUSION: FAP expression identifies CMS4 CRC. FAPI-PET may have value in the comprehensive detection of CMS4 tumours in CRC. This is especially relevant in patients with PM, for whom effective imaging tools are currently lacking.
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Neoplasias Colorrectales , Neoplasias Peritoneales , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Fibroblastos/patología , Radioisótopos de Galio/uso terapéutico , Humanos , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de PositronesRESUMEN
INTRODUCTION: The optimal time interval between diagnostic excision of a primary cutaneous melanoma and sentinel node (SN) biopsy is unknown. The current study sought to determine whether this interval influenced the SN-positivity rate, recurrence or survival. METHODS: Data collected from 2004 to 2014 for a Dutch population-based cohort of patients with melanoma who underwent SN biopsy (SNB) within 100 days of initial diagnosis (n = 7660) and for a similarly specified cohort from a large Australian melanoma treatment centre (n = 3478) were analysed. Time to SNB was analysed continuously (in weeks) and categorically (per month). The effects of SNB timing on SN-positivity were assessed using multivariable logistic regression, and its effects on recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox proportional hazard regression analyses. Advanced modelling using a multivariable Cox model with penalised splines for modelling the continuous effects of time to SNB on RFS and OS was also performed. RESULTS: In neither the Dutch nor the Australian cohort was there a significant association between time to SNB and SN-positivity in either cohort, nor was there an impact of time to SNB on RFS or OS in either cohort. The spline-based HR curves for RFS and OS confirmed these findings. CONCLUSIONS: The time interval between diagnostic excision of a primary melanoma and SNB did not influence the SN-positivity rate or survival outcomes. This provides reassurance that neither early nor delayed definitive wide excision and SNB will adversely affect prognosis.
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Melanoma , Neoplasias Cutáneas , Australia , Humanos , Melanoma/patología , Pronóstico , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , SíndromeRESUMEN
INTRODUCTION: This study sought to assess whether the interval between diagnostic excision-biopsy of a primary melanoma and definitive wide excision with sentinel node biopsy (SNB) influenced the size of SN metastatic deposits, which might have implications for management and prognosis. METHODS: Data were collected for (i) a Dutch population-based cohort of patients treated between 2004 and 2014 who underwent SNB within 100 days of complete excision of their primary melanoma and who were SN-positive with known SN metastasis diameter (n = 1027) and (ii) a cohort from a large Australian melanoma treatment centre (n = 541) who presented in the same time period. The effects of SNB timing on the size of SN metastatic deposits were analysed. RESULTS: Dutch patients whose SNB was performed in the second or third months after diagnosis had significantly larger SN metastasis diameters than patients who had their SNB in the first month (median increases of 17% (95%CI -14, 60%, p = 0.211) and 71% (95%CI 15, 119%, p = 0.004), respectively). No significant difference in tumour diameter for early and late SNB was found in the Australian cohort. CONCLUSIONS: SN metastasis diameter became progressively greater with SN biopsy in the second and third months after primary melanoma diagnosis in the larger, population-based patient cohort. An increase in metastasis diameter was not observed in the smaller, institutional cohort, possibly due to detection of larger SN metastases by routine pre-operative ultrasound, with fine-needle biopsy confirmation. These patients did not proceed to SNB and were therefore not included in the study.
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Melanoma , Neoplasias Primarias Secundarias , Neoplasias Cutáneas , Australia , Extensión Extranodal , Humanos , Escisión del Ganglio Linfático , Melanoma/patología , Melanoma/cirugía , Neoplasias Primarias Secundarias/cirugía , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , SíndromeRESUMEN
BACKGROUND: Survival tends to decrease as the Breslow thickness of a primary melanoma increases. However, little is known about the prognostic value of Breslow thickness in patients with very thick melanomas. OBJECTIVE: We sought to assess survival in patients with melanomas ≥4.0 mm in Breslow thickness. METHODS: A pooled cohort of 5595 patients (4107 Dutch and 1488 Australian) with melanomas ≥4.0 mm in thickness diagnosed from 2000 to 2014 was analyzed. Standard and spline Cox regressions were generated for overall survival (OS) and recurrence-free survival (RFS). RESULTS: The median follow-up was 3.4 years. The continuous hazard ratios (HRs) for OS and RFS increased steadily as the Breslow thickness increased to 15 mm, stabilized up to 20 mm, and decreased thereafter. Using patients with melanomas 4 to <10 mm thick as a reference group, the categoric HR for OS increased up to the 15- to -<20-mm thickness category and then decreased (HR, 1.46 [95% CI, 1.29-1.66], P < .0001 for 10-<15 mm; HR, 1.97 [95% CI, 1.55-2.51], P < .0001 for 15-<20 mm; and HR, 1.36 [95% CI, 1.07-1.84], P = .045 for ≥20 mm). For the RFS, similar trends were observed. LIMITATIONS: Retrospective study. Small cohorts of patients with melanomas 15-<20mm and ≥20mm. CONCLUSION: The progressive relationship between increasing Breslow thickness and decreasing survival is lost in patients with melanomas ≥15 mm in thickness.
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Melanoma , Neoplasias Cutáneas , Australia/epidemiología , Humanos , Melanoma/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: The aim of this study was to develop a patient decision aid (pDA) that could support patients with breast cancer (BC) in making an informed decision about breast reconstruction (BR) after mastectomy. METHODS: The development included four stages: (i) Establishment of a multidisciplinary team; (ii) Needs assessment consisting of semi-structured interviews in patients and a survey among healthcare professionals (HCPs); (iii) Creation of content, design and technical system; and (iv) Acceptability and usability testing using a think-aloud approach in patients and interviews among HCPs and representatives of the Dutch Breast Cancer Patient Organization. RESULTS: From the needs assessment, three themes were identified: Challenging period to make a decision, Diverse motivations for a personal decision and Information needed to make a decision about BR. HCPs valued the development of a pDA, especially to prepare patients for consultation. The pDA that was developed contained three parts: first, a consultation sheet for oncological breast surgeons to introduce the choice; second, an online tool including an overview of reconstructive options, the pros and cons of each option, information on the consequences of each option for daily life, exercises to clarify personal values and patient stories; and third, a summary sheet with patients' values, preferences and questions to help inform and guide the discussion between the patient and her plastic surgeon. The pDA was perceived to be informative, helpful and easy to use by patients and HCPs. CONCLUSION: Consistent with information needs, a pDA was developed to support patients with BC who consider immediate BR in making an informed decision together with their plastic surgeon. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in the needs assessment and in acceptability and usability testing.
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Neoplasias de la Mama , Técnicas de Apoyo para la Decisión , Mamoplastia , Neoplasias de la Mama/cirugía , Toma de Decisiones , Femenino , Humanos , Mastectomía , MotivaciónRESUMEN
Importance: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). Objective: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. Design, Setting, and Participants: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. Interventions: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. Main Outcomes and Measures: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). Results: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. Conclusions and Relevance: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02758951.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/terapia , Adenocarcinoma/secundario , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Capecitabina/administración & dosificación , Quimioterapia Adyuvante/efectos adversos , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Terapia Neoadyuvante , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino/administración & dosificación , Periodo Perioperatorio , Neoplasias Peritoneales/secundario , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
INTRODUCTION: Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for patients with stage III melanoma. Studies re-evaluating the diagnosis of initially positive SN biopsies are scarce. MATERIALS AND METHODS: Dutch patients with melanoma who underwent SN biopsy between 2003 and 2014 were selected from PALGA, the Dutch Pathology Registry. Histopathological slides of SN-positive patients were retrieved for review. A random sample was reassessed by an expert melanoma pathologist. Recurrence-free survival (RFS) of patients who were misclassified (false-positive) was compared with those with a true positive SN status. For comparison, a group of SN-negative patients was included. Multivariable logistic analysis was performed to assess clinicopathological characteristics associated with misclassification of SN status. RESULTS: Diagnosis was downgraded from melanoma metastasis to nodal nevus in 38 of the 322 reviewed patients (11.8%). Considering the inclusion criteria of phase III adjuvant trials, at least 4.3% of patients would have falsely qualified for adjuvant therapy. In multivariable analysis, patients with a low SN tumour burden and subcapsular SN tumour location had a significantly higher chance of being misclassified. The five-year RFS of the 38 downgraded patients was 86.7% (95% confidence interval [CI] = 72.6-96.6), similar to the 85.9% (95% CI = 84.9-86.8, p = 0.18) for 6413 SN-negative patients and better than the 53.2% (95% CI = 47.2-59.9, p = 0.009) of 284 patients who were truly SN positive upon review. CONCLUSION: More than 10% of originally positive SN biopsies of patients with melanoma concern misclassified nodal nevi. We advocate that when adjuvant treatment is considered in patients with stage III melanoma, SN biopsies should be reassessed by an expert melanoma pathologist.
Asunto(s)
Toma de Decisiones Clínicas , Melanoma/secundario , Ganglio Linfático Centinela/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Terapia Combinada , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Melanoma/terapia , Persona de Mediana Edad , Estadificación de Neoplasias , Países Bajos , Variaciones Dependientes del Observador , Selección de Paciente , Valor Predictivo de las Pruebas , Sistema de Registros , Reproducibilidad de los Resultados , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/terapia , Resultado del Tratamiento , Procedimientos InnecesariosRESUMEN
PURPOSE: Although the prognosis of patients with thin primary cutaneous melanomas (T1, ≤ 1.0 mm) is generally excellent, some develop recurrence. We sought to develop and validate a model predicting recurrences in patients with thin melanomas. METHODS: A Dutch population-based cohort (n = 25,930, development set) and a cohort from an Australian melanoma treatment center (n = 2,968, validation set) were analyzed (median follow-up 6.7 and 12.0 years, respectively). Multivariable Cox models were generated for local, regional, and distant recurrence-free survival (RFS). Discrimination was assessed using Harrell's C-statistic for each outcome. Each nomogram performance was evaluated using calibration plots defining low-risk and high-risk groups as the lowest and top 5% of the nomogram risk score, respectively. The nomograms' C-statistics were compared with those of a model including the current American Joint Committee on Cancer staging parameters (T-stage and sentinel node status). RESULTS: Local, regional, and distant recurrences were found in 209 (0.8%), 503 (1.9%), and 203 (0.8%) Dutch patients, respectively, and 23 (0.8%), 61 (2.1%), and 75 (2.5%) Australian patients, respectively. C-statistics of 0.79 (95% CI, 0.75 to 0.82) for local RFS, 0.77 (95% CI, 0.75 to 0.78) for regional RFS, and 0.80 (95% CI, 0.77 to 0.83) for distant RFS were obtained for the development model. External validation showed C-statistics of 0.80 (95% CI, 0.69 to 0.90), 0.76 (95% CI, 0.70 to 0.82), and 0.74 (95% CI, 0.69 to 0.80), respectively. Calibration plots showed a good match between predicted and observed rates. Using the nomogram, the C-statistic was increased by 9%-12% for the development cohort and by 11%-15% for the validation cohort, compared with a model including only T-stage and sentinel node status. CONCLUSION: Most patients with thin melanomas have an excellent prognosis, but some develop recurrence. The presented nomograms can accurately identify a subgroup at high risk. An online calculator is available at www.melanomarisk.org.au.