Older patients are believed to prefer a more passive role in decision making. This prospective study surveyed younger and older patients undergoing treatment for early breast cancer. Older patients ...most frequently preferred to decide with their clinician, although they often felt they had a passive role. It is important to elicit the preferred role of all patients, regardless of their age.
Older patients are believed to prefer a more passive role in treatment decision making, but studies reporting this relation were conducted over a decade ago or were retrospective. We prospectively compared younger (40-64 years) versus older (≥ 65 years) breast cancer patients' preferences for decision-making roles and their perceived actual roles.
A prospective multicenter study was conducted in Leiden, The Hague, and Tilburg over a 2-year period. Early-stage breast cancer patients were surveyed about their preferred and perceived decision-making roles (active, shared, or passive) concerning surgery type (breast-conserving vs. mastectomy) (n = 74), adjuvant chemotherapy (aCT, n = 43), and adjuvant hormonal therapy (aHT, n = 39).
For all decisions, both age groups most frequently preferred a shared role before consultation, except for decisions about aHT, for which younger patients more commonly preferred an active role. The proportion of patients favoring an active or passive role in each decision was lower for the older than the younger patients, but none of the differences was significant. Regarding perceived actual roles, both groups most frequently reported an active role in the surgical decision after consultation. In deciding about both aCT and aHT, a larger proportion of older patients perceived having had a passive role compared to younger patients, and a greater proportion of younger patients perceived having been active. Again, differences were not statistically significant.
Most older patients preferred to decide together with their clinician, but preferences varied widely. Older patients more often than younger patients perceived they had not been involved in decisions about systemic therapy. Clinicians should invite all patients to participate in decision making and elicit their preferred role.
IntroductionTreatment with anti-PD-1 immunotherapy does not lead to long-lasting clinical responses in approximately 60% of patients with metastatic melanoma. These refractory patients, however, can ...still respond to treatment with tumour infiltrating lymphocytes (TIL) and interferon-alpha (IFNa). A combination of TIL, pegylated-interferon-alpha (PEG-IFNa) and anti-PD-1 is expected to provide a safe, feasible and effective therapy for patients with metastatic melanoma, who are refractory to standard of care treatment options.Methods and analysisPatients are treated in two phases. In phase I, the safety of the combination TIL and anti-PD-1 is assessed (cohort 1) according to CTCAE 4.03 criteria. Subsequently, the safety of cotreatment with PEG-IFNa is tested in cohort 2. The efficacy will be evaluated in the second phase of the trial. Efficacy is evaluated according to RECIST 1.1 and immune-related response criteria. Clinical and immunological parameters will be evaluated for their relation with clinical responsiveness.Ethics and disseminationEthical approval of the trial was obtained from the Central Committee on Research Involving Human Subjects in the Netherlands. The trial results will be shared with the scientific community at (inter)national conferences and by publication in a peer-reviewed journal.Trial registration numberNCT03638375; Pre-results.
Near-infrared (NIR) fluorescence imaging has the potential to improve sentinel lymph node (SLN) mapping in breast cancer. Indocyanine green (ICG) is currently the only clinically available ...fluorophore that can be used for SLN mapping. Preclinically, ICG adsorbed to human serum albumin (ICG:HSA) improves its performance as a lymphatic tracer in some anatomical sites. The benefit of ICG:HSA for SLN mapping of breast cancer has not yet been assessed in a clinical trial. We performed a double-blind, randomized study to determine if ICG:HSA has advantages over ICG alone. The primary endpoint was the fluorescence brightness, defined as the signal-to-background ratio (SBR), of identified SLNs. Clinical trial subjects were 18 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using
99m
Technetium-nanocolloid and patent blue. Patients were randomly assigned to receive 1.6 ml of 500 μM ICG:HSA or ICG that was injected periareolarly directly after patent blue. The Mini-Fluorescence-Assisted Resection and Exploration (Mini-FLARE) imaging system was used for NIR fluorescence detection and quantitation. SLN mapping was successful in all patients. Patient, tumor, and treatment characteristics were equally distributed over the treatment groups. No significant difference was found in SBR between the ICG:HSA group and the ICG alone group (8.4 vs. 11.3, respectively,
P
= 0.18). In both groups, the average number of detected SLNs was 1.4 ± 0.5 SLNs per patient (
P
= 0.74). This study shows that there is no direct benefit of premixing ICG with HSA prior to injection for SLN mapping in breast cancer patients, thereby reducing the cost and complexity of the procedure. With these optimized parameters that eliminate the necessity of HSA, larger trials can now be performed to determine patient benefit.
Breast cancer is one of the primary indications for cryopreservation and subsequent autotransplantation of ovarian tissue. The safety of this fertility preservation method remains questionable, as ...the presence of disseminated breast tumor cells cannot yet be excluded in the ovarian autografts. We explored the prevalence of ovarian metastases among young breast cancer patients and determined risk factors for the development of ovarian metastases.
Using the nationwide database of the Dutch Pathology Registry (PALGA), we identified a cohort of 2648 women with primary invasive breast cancer at age < 41 years in the period 2000-2010 in the Netherlands who subsequently underwent an oophorectomy. From this source population, all cases who had histologically confirmed ovarian metastases were included. For each case of whom clinical data were available, one control without ovarian metastases who matched the time interval between breast cancer diagnosis and oophorectomy was selected. Data were collected on patient characteristics, diagnosis, treatment and follow-up.
Ovarian metastases were found in 63 out of 2648 patients who met the inclusion criteria. The risk of developing ovarian metastases increased with time passed since breast cancer diagnosis. Multivariate logistic regression analyses showed significant association between tumor stage and the development of ovarian metastases (p = 0.024).
The prevalence of ovarian metastases was 2.4% among young breast cancer patients. Early ovary removal may reduce the risk of developing ovarian metastases. In breast cancer patients with tumors > 5 cm and/or inflammatory carcinoma, we recommend a cautious approach to ovarian tissue autotransplantation.
Background
Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.
Materials and Methods
A small, portable version ...of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using
99m
Technetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM.
Results
The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1–3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed.
Conclusions
We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.
Background.
The number of elderly women with breast cancer is increasing and will become a major health concern. However, little is known about the optimal treatment for this age group. The aim of ...this study was to describe time trends for the overall Dutch breast cancer cohort with an emphasis on differences between young and elderly patients.
Methods.
All adult female patients diagnosed in 1995–2005 were selected from the Netherlands Cancer Registry. Relative excess risks for death (adjusted for stage, histology, treatment, and grade) were estimated using a multivariate generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times.
Results.
Overall, 127,805 patients were included. Treatment of patients aged ≥75 years changed significantly over time: they received less surgery, more adjuvant hormonal treatment and chemotherapy, and more hormonal treatment without surgery. In contrast to younger patients, the relative survival did not improve significantly over time for elderly patients. With increasing age, the observed–expected death ratio decreased to almost 1.0.
Conclusion.
Survival for elderly patients with breast cancer did not improve significantly. Observed–expected death ratios in the elderly are close to 1, indicating that excess mortality is low. Elderly patients with breast cancer have a higher risk for overtreatment and undertreatment, with a delicate therapeutic balance between breast cancer survival gain and potential toxicities. To improve breast cancer survival in the elderly, a critical reappraisal is needed of costs and benefits of hormonal as well as other treatments, and better selection of patients who can benefit from available therapies is warranted.
摘要
背景. 乳腺癌老年患者日益增多，已成为一个重点关注的健康问题。然而，该年龄段患者群体的最佳治疗知之甚少。本研究旨在明确荷兰国内乳腺癌的总体发病年龄趋势，着眼于年轻患者与老年患者的内在差异。
方法. 研究对象为荷兰癌症登记处记录的1995～2005年间所有确诊的乳腺癌成年女性患者。采用确切生存时间，基于相对存活率的组合数据，运用Poisson分布多变量广义线性模型评估（经过分期、组织学、治疗及分级调整后的）死亡的相对超额风险。
结果. 共纳入127,805例患者。年龄≥75岁患者的治疗模式随时间进程而显著变化：较少接受手术治疗，更易接受激素辅助治疗及化疗、或单纯激素治疗。相对于年轻患者，老年患者的相对存活率并未随时代发展明显改善。随着年龄增长，观察/预期死亡比几乎降低至1.0。
结论. 乳腺癌老年患者的生存无明显改善。老年患者的观察/预期死亡比接近于1，表明超额死亡率低。老年乳腺癌患者过度治疗或治疗不足的风险较高，治疗所能得到的生存获益与其潜在毒性间存在微妙的平衡。为了改善老年患者的生存，对激素治疗及其他疗法的成本效益进行重新评估，当务之急是有效筛选出可从现有治疗模式中获益的患者。
The relative survival of breast cancer patients diagnosed in 1995–2005 from the Netherlands Cancer Registry was examined and stratified by age group. In contrast to younger patients and in spite of similarly intensified treatment, the relative survival of elderly patients showed no improvement over this time period.
Standard treatment of colorectal cancer includes adjuvant chemotherapy for patients with stage III disease (defined by the presence of lymph-node metastases), but not for patients with stage II ...tumors (who have no lymph-node metastases). However, 20 percent of patients with stage II tumors die of recurrent disease. We investigated whether the detection of micrometastases can be used to identify patients with stage II disease who are at high risk for recurrence.
We analyzed 192 lymph nodes from 26 consecutive patients with stage II colorectal cancer, using a carcinoembryonic antigen-specific nested reverse-transcriptase polymerase chain reaction. Five-year follow-up information was obtained on all patients. Observed and adjusted survival rates were assessed in the patients with and the patients without micrometastases.
Micrometastases were detected in one or more lymph nodes from 14 of 26 patients (54 percent). The adjusted five-year survival rate (for which only cancer-related deaths were considered) was 50 percent in this group, whereas in the 12 patients without micrometastases, the survival rate was 91 percent (P=0.02 by the log-rank test). The observed five-year survival rates were 36 percent and 75 percent, respectively (P=0.03). The groups were similar with respect to age, sex, tumor side (location in relation to the flexura lienalis), degree of tumor differentiation (grade), and diameter of the primary tumor.
Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer.
Background.
Early discontinuation of adjuvant endocrine therapy may affect the outcome of treatment in breast cancer patients. The aim of this study was to assess age‐specific persistence and ...age‐specific survival outcome based on persistence status.
Methods.
Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational trial were included. Nonpersistence was defined as discontinuing the assigned endocrine treatment within 1 year of follow‐up because of adverse events, intercurrent illness, patient refusal, or other reasons. Endpoints were the breast cancer–specific and overall survival times. Analyses were stratified by age at diagnosis (<65 years, 65–74 years, ≥75 years).
Results.
Overall, 3,142 postmenopausal breast cancer patients were included: 1,682 were aged <65 years, 951 were aged 65–74 years, and 509 were aged ≥75 years. Older age was associated with a higher proportion of nonpersistence within 1 year of follow‐up. In patients aged <65 years, nonpersistent patients had lower breast cancer–specific and overall survival probabilities. In patients aged 65–74 years and patients aged ≥75 years, the survival times of persistent and nonpersistent patients were similar.
Conclusion.
Nonpersistence within 1 year of follow‐up was associated with lower breast cancer–specific and overall survival probabilities in patients aged <65 years, but it was not associated with survival outcomes in patients aged 65–74 years or in patients aged ≥75 years. These results suggest that extrapolation of outcomes from a young to an elderly breast cancer population may be insufficient and urge age‐specific breast cancer studies.
摘要
背景. 早期终止辅助性内分泌治疗可影响乳腺癌患者治疗的转归。本研究旨在按持续状态，评估年龄特异性持续性和年龄特异性生存转归。
方法. 入组他莫昔芬和依西美坦辅助多国试验的患者纳入研究，非持续性的定义为随访1年内因不良事件、间发疾病、患者拒绝或其他原因终止所分配的内分泌治疗。终点为乳腺癌特异性生存时间和总生存时间。分析时按确诊时年龄分层（<65岁、65~74岁和³75岁）。
结果. 总计3142例绝经后乳腺癌患者纳入研究，其中<65岁、65~74岁和³75岁分别有1682例、951例和509例。高龄与随访1年内非持续性比例较高关联。<65岁患者中，非持续患者的乳腺癌特异性生存率和总生存率较低。65~74岁和³75岁的患者中，持续者的生存时间与非持续者相似。
结论. 随访1年内非持续性与<65岁患者的乳腺癌特异性生存率和总生存率较低关联，但与65~74岁和³75岁患者的生存转归无关联。上述结果提示，乳腺癌患者中，低龄群体的转归可能不足以推衍至高龄群体，乳腺癌研究须按年龄进行分层。
Age‐specific nonpersistence with endocrine therapy within 1 year of follow‐up was assessed in breast cancer patients, and age‐specific outcome by nonpersistence status at 1 year of follow‐up was evaluated. Nonpersistence was associated with lower breast cancer–specific and overall survival probabilities in patients aged <65 years but not in older patients.
Abstract Background Neoadjuvant hormonal therapy (NHT) is playing an increasing role in the clinical management of breast cancer (BC) and may improve surgical outcomes for postmenopausal, oestrogen ...receptor (ER)-positive BC patients. However, there is currently no consensus on the optimal duration of NHT before surgery. Here, we present the outcomes of the TEAM IIA trial, a multicentre, phase II trial investigating the efficacy of six months of neoadjuvant exemestane in postmenopausal, strong ER-positive (ER+, ⩾50%) BC patients. Methods 102 patients (stage T2-T4ac) were included in the study after exclusion of ineligible patients. Primary end-point was clinical response at 3 and 6 months as measured by palpation. Secondary end-point was radiological response as measured by magnetic resonance imaging (MRI), mammography and/or ultrasound. Linear mixed models (95% confidence interval (CI)) were used to compare changes in mean tumour size (in mm) between baseline, 3 and 6 months after the start of endocrine therapy. Conversion rates from mastectomy to breast conserving surgery (BCS) were evaluated. Results Median age of all patients was 72 years (range 53–88). Overall response rate by clinical palpation was 64.5% in all patients with a final palpation measurement. Four patients had clinically progressive disease. 63 patients had both 3-month and >3-month palpation measurements. Overall response was 58.7% at 3 months and 68.3% at final palpation (>3 months). Mean tumour size by clinical palpation at T = 0 was 39.1 mm (95% CI 34.8–43.4 mm), and decreased to 23.0 mm (95% CI 18.7–27.2 mm) and 16.7 mm (95% CI 12.6–20.8) at T = 3 and T > 3 months, respectively ( p = 0.001). Final radiological response rates at the end of treatment for MRI ( n = 37), ultrasound ( n = 77) and mammography ( n = 56) were 70.3%, 41.6% and 48.2%, respectively. Feasibility of BCS improved from 61.8% to 70.6% (McNemar p = 0.012). Conclusion 6 months of neoadjuvant exemestane therapy helps reduce mean tumour size further in strongly ER-positive BC patients without significant side-effects compared to 3 months. Nevertheless, some patients still experience disease progression under exemestane. Feasibility of breast conservation rates improved by almost 10%.
The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancer patients. We conducted a prospectively designed study to validate this assay for ...prediction of recurrence risk in stage II and III rectal cancer patients from the Dutch Total Mesorectal Excision (TME) trial.
RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time-polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided.
Recurrence Score predicted risk of recurrence (hazard ratio HR = 1.57, 95% confidence interval CI = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (P(interaction) ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients).
The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancer patients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers.
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