Treatment and survival of patients diagnosed with high-risk HR+/HER2- breast cancer in the Netherlands: a population-based retrospective cohort study.

BACKGROUND: Several factors may increase the risk of recurrence of patients diagnosed with hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). We aim to determine the proportion of patients with high-risk HR+/HER2- BC within the total HR+/HER2- BC cohort and compare their systemic treatments and survival rates with those of patients with low- and intermediate-risk HR+/HER2- BC and triple-negative (TN) BC. PATIENTS AND METHODS: Women diagnosed with nonmetastatic invasive HR+/HER2- BC and TNBC in the Netherlands between 2011 and 2019 were identified from the Netherlands Cancer Registry. Patients with HR+/HER2- BC were categorised according to risk profile, defined by nodal status, tumour size, and histological grade. High-risk HR+/HER2- BC was defined by either four or more positive lymph nodes or one to three positive lymph nodes with a tumour size of ≥5 cm or a histological grade 3 tumour. Overall survival (OS) and relative survival (RS) were calculated using the Kaplan-Meier and Pohar-Perme method. RESULTS: In this study of 87 455 patients with HR+/HER2- BC, 44 078 (50%) patients were diagnosed with low risk, 28 452 (33%) with intermediate risk, and 11 285 (13%) with high-risk HR+/HER2- BC. In 3640 (4%) patients, the risk profile could not be defined. Endocrine therapy and chemotherapy were used in 38% and 7% of low-risk, 90% and 47% of intermediate-risk, and 94% and 73% of high-risk patients, respectively. The 10-year OS and RS rates were 84.1% [95% confidence interval (95% CI) 83.5% to 84.7%] and 98.7% (95% CI 97.3% to 99.4%) in low-risk, 75.1% (95% CI 74.2% to 76.0%) and 91.7% (95% CI 89.7% to 93.3%) in intermediate-risk, and 63.4% (95% CI 62.0% to 64.7%) and 72.3% (70.1% to 74.3%) in high-risk patients. The 10-year OS and RS rates of 12 689 patients with TNBC were 69.7% (95% CI 68.6% to 70.8%) and 79.1% (95% CI 77.0% to 80.9%), respectively. CONCLUSION: The poor prognosis of patients with high-risk HR+/HER2- BC highlights the need for a better acknowledgement of this subgroup and supports ongoing clinical trials aimed at optimising systemic therapy.

Oncologic management of ampullary cancer: International survey among surgical and medical oncologists.

BACKGROUND: Ampullary adenocarcinoma (AAC) is a rare neoplasm which as a result is lacking specific treatment guidelines. This international survey study was performed to gain insight in the current daily practice of AAC. METHODS: Surgeons and medical oncologists, whom were members of the Dutch Pancreatic Cancer Group, International Study Group on Ampullary Cancer, International Hepato-Pancreato-Biliary Association, European and International Consortium on Minimally Invasive Pancreatic Surgery, or contributed to (peri)ampullary cancer research, were invited through email and newsletters between January and October 2021. RESULTS: Overall, 217 surgeons and medical oncologists completed the survey. Most of the respondents work in Europe (60%), and in a pancreatic expertise center (86%). The majority of respondents (87%) stated that the histological AAC subtype (e.g. intestinal vs. pancreatobiliary) was determined in the resection specimen. Neoadjuvant treatment for resectable disease was considered by 24% and adjuvant therapy by 90% of the respondents, with 80% of them choosing adjuvant chemotherapy alone. The formation of multidisciplinary teams, improvement in resection procedures, increased availability of chemotherapy regimens, and increased knowledge on tumor biology were considered as the most important developments in the last five years. The necessity for randomized controlled trials was mentioned by 50% of the respondents. CONCLUSIONS: This international survey highlights the existing variation in the management of patients with AAC, especially regarding the use of (neo)adjuvant therapy. More data from trials and international registries are needed to develop evidence-based guidelines on surgical and oncological management with the ultimate aim to improve outcomes for patients with AAC.

[Personalised follow-ups for patients curatively treated for squamous cell carcinoma in the oral cavity]. / Gepersonaliseerde nacontrole bij patiënten die curatief zijn behandeld voor een plaveiselcelcarcinoom in de mondholte.

As a result of an increase in the incidence of oral cancer and improving survival rates, the number of patients needing follow-up care will increase in the Netherlands. At present, these patients enroll in a 5-year follow-up programme aiming for early detection of recurrences or second primary tumors and improving their prognosis of life expectancy, among other things. Recurrences mostly occur in the first 2 years after treatment, whereas patients have a lifelong elevated risk of second primary tumors. 75% of second primary tumors occur outside the oral cavity and over 50% outside the head and neck area, places not routinely checked. There is no convincing evidence this 5-year follow-up programme yields survival benefits. It would therefore be better to limit follow-up care to 2 years and choose a subsequent follow-up programme better tailored to the individual patient's needs. This does not necessarily require the lead of a head and neck oncologist.

Patterns of recurrence following definitive chemoradiation for patients with proximal esophageal cancer.

INTRODUCTION: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer. MATERIALS AND METHODS: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses. RESULTS: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached). CONCLUSION: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years.

The relative effectiveness of eribulin for advanced breast cancer treatment: a study of the southeast Netherlands advanced breast cancer registry.

Background: Eribulin provided significant overall survival (OS) benefit in heavily pretreated advanced breast cancer patients in the EMBRACE trial. We investigated the use of eribulin in daily clinical practice, the relative effectiveness of eribulin versus non-eribulin chemotherapy, and the safety of eribulin in real-world patients included in the SOutheast Netherlands Advanced BREast cancer (SONABRE) registry.Material and methods: Patients treated with eribulin and eligible patients for eribulin who received a different chemotherapy (i.e., non-eribulin group) in ten hospitals in 2013-2017 were included. A multivariate matching algorithm was applied to correct for differences in baseline characteristics between the groups, including the number of previous treatment lines. Progression-free survival (PFS) and OS of eribulin were compared with the matched non-eribulin group through Kaplan-Meier curves and multivariate Cox proportional hazard models. The occurrence of dose delay and reduction was described.Results: Forty-five patients received eribulin according to its registration criteria and 74 patients were eligible for eribulin but received non-eribulin chemotherapy. Matching increased the similarity in baseline characteristics between the eribulin and non-eribulin groups. Median PFS was 3.5 months (95% confidence interval (CI): 2.7-5.5) in the eribulin group and 3.2 months (95% CI: 2.0-4.8) in the matched non-eribulin group (adjusted hazard ratio (HR): 0.83, 95% CI: 0.49-1.38). Median OS was 5.9 months (95% CI: 4.6-11.0) and 5.2 months (95% CI: 4.6-9.5) in the eribulin and non-eribulin groups, respectively (adjusted HR: 0.66, 95% CI: 0.38-1.13). Dose delay or reduction occurred in 14 patients (31%) receiving eribulin.Conclusions: No difference in PFS and OS was observed between eribulin and non-eribulin treated patients. Eribulin had a manageable toxicity profile.

Population-based study of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ.

BACKGROUND: Determinants of the use of breast MRI in patients with ductal carcinoma in situ (DCIS) in the Netherlands were studied, and whether using MRI influenced the rates of positive resection margins and mastectomies. METHODS: All women aged less than 75 years, and diagnosed with DCIS between 2011 and 2015, were identified from the Netherlands Cancer Registry. Multivariable logistic regression analyses were performed, adjusting for incidence year, age, hospital type, DCIS grade and multifocality. RESULTS: Breast MRI was performed in 2382 of 10 415 DCIS cases (22·9 per cent). In multivariable analysis, patients aged less than 50 years, those with high- or intermediate-grade DCIS and patients with multifocal disease were significantly more likely to have preoperative MRI. Patients undergoing MRI were more likely to have a mastectomy, either as first surgical treatment or following breast-conserving surgery (BCS) in the event of positive margins (odds ratio (OR) 2·11, 95 per cent c.i. 1·91 to 2·33). The risk of positive surgical margins after BCS was similar for those with versus without MRI. The secondary mastectomy rate after BCS was higher in patients who had MRI, especially in women aged less than 50 years (OR 1·94, 1·31 to 2·89). All findings were similar for low- and intermediate/high-grade DCIS. CONCLUSION: Adding MRI to conventional breast imaging did not improve surgical outcome in patients diagnosed with primary DCIS. The likelihood of undergoing a mastectomy was twice as high in the MRI group, and no reduction in the risk of margin involvement was observed after BCS.

ANTECEDENTES: Se estudiaron los determinantes del uso de la resonancia magnética (RM) de mama en pacientes con carcinoma ductal in situ (ductal carcinoma in situ, DCIS) en los Países Bajos y si el uso de la RM influía en las tasas de márgenes de resección positivos y de mastectomías. MÉTODOS: Todas las mujeres menores de 76 años de edad y diagnosticadas de DCIS fueron identificadas a partir del Registro de Cáncer de los Países Bajos de 2011-2015. Se realizaron análisis de regresión logística multivariable, ajustando por año de incidencia, edad, tipo de hospital, grado de DCIS y multifocalidad. RESULTADOS: Se realizó una RM de mama en 2.382 de 10.415 (23%) pacientes con DCIS. En el análisis multivariable, en las pacientes de edad < 50 años, con DCIS de grado alto o intermedio y enfermedad multifocal era estadísticamente significativo más probable que se sometieran a una RM preoperatoria. Las pacientes que se sometieron a RM tuvieron más probabilidades de que se efectuara una mastectomía, ya fuera como primer tratamiento quirúrgico o después de una cirugía conservadora de mama (breast conserving surgery, BCS) en el caso de presentar márgenes positivos (razón de oportunidades, odds ratio, OR = 2,1, i.c. del 95%: 1,9-2,3). El riesgo de obtener márgenes quirúrgicos positivos después de la BCS fue similar para aquellas pacientes con RM versus sin RM. Sin embargo, la tasa de mastectomía secundaria después de la BCS fue mayor en pacientes con RM, especialmente en mujeres menores de 50 años (OR = 1,9, i.c. del 95%: 1,3-2,9). CONCLUSIÓN: Agregar la RM a las imágenes radiológicas convencionales de mama no mejoró el resultado quirúrgico en pacientes diagnosticadas de DCIS primario. En el grupo de RM, la probabilidad de someterse a una mastectomía fue dos veces más alta, sin observarse una reducción en el riesgo de afectación del margen después de la BCS.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

A real-life study on the implementation and effectiveness of exemestane plus everolimus per hospital type in patients with advanced breast cancer. A study of the Southeast Netherlands Advanced Breast Cancer registry.

PURPOSE: We aimed to assess the implementation and effectiveness of exemestane plus everolimus treatment per hospital type in real-life, shortly after approval of everolimus. METHODS: Advanced breast cancer patients treated with exemestane plus everolimus in 2012-2014 were included from the SONABRE registry. Progression-free survival (PFS) and a 12-week conditional PFS (post-hoc) were estimated by Kaplan-Meier method. The multivariable Cox proportional hazards model was performed by type of hospital and adjusted for patient, tumour and treatment characteristics. RESULTS: We included 122 patients, comprising 48 patients treated in academic (N = 1), 56 in teaching (N = 4), and 18 in non-teaching (N = 2) hospitals. The median PFS was 6.3 months (95% Confidence Interval (CI) 4.0-8.6) overall, and 8.5 months (95% CI 7.7-9.3), 4.2 months (95% CI 2.0-6.3), and 5.5 months (95% CI 4.2-6.7) for the patients treated in academic, teaching and non-teaching hospitals, respectively. The adjusted Hazard Ratio (HR) for PFS-events was 1.5 (95% CI 1.0-2.2) and 1.0 (95% CI 0.5-1.9) respectively for patients treated at teaching and non-teaching hospitals versus the academic hospital. The adjusted HR for 12-week conditional PFS-events was not different between hospital types. In the first 12-week treatment period, treatment was discontinued due to early progression in one out of 48 patients in the academic versus nine out of 74 patients in the non-academic hospitals, confirmed by imaging in one and two patients, respectively. CONCLUSIONS: In our study, the median PFS was borderline significantly different between hospital types, possibly the result of a different assessment approach in the first 12-week treatment period.

Follow-up after curative treatment for oral squamous cell carcinoma. A critical appraisal of the guidelines and a review of the literature.

The oral cavity is the commonest subsite of head and neck squamous cell carcinoma (HNSCC). Because of the rising incidence and increasing survival, more patients will be enrolled in a routine follow-up program. This review gives an overview of the evidence and guideline recommendations concerning follow-up after oral squamous cell carcinoma (OSCC). There is limited evidence concerning the effectiveness of follow-up after OSCC. This lack of evidence is reflected in a variation in guideline recommendations with respect to test interval and duration (i.e. for 3-5 years or lifelong). Most studies on the value of routine follow-up after curative treatment include all HNSCC subsites. The available literature shows, that these subsites have a different timing of recurrence and a different risk of second primary tumors at different locations. This leaves no rationale for applying the same follow-up program to each of the HNSCC subsites. There is agreement in the literature that OSCC follow-up can either be discontinued after two or three years or should be lifelong based on the risk of second primary tumors. Many authors advocate a personalized follow-up regimen that is based on the risk of new disease rather than a one-size-fits-all surveillance program. The literature is conflicting about the survival benefits of asymptomatic detection of new disease for HNSCC. To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own follow-up regimen.

Likely effect of adding flexible sigmoidoscopy to the English NHS Bowel Cancer Screening Programme: impact on colorectal cancer cases and deaths.

BACKGROUND: From 2013, once-only flexible sigmoidoscopy (FS) at age 55 is being phased into the England National Health Service Bowel Cancer Screening Programme (NHSBCSP), augmenting biennial guaiac faecal occult blood testing (gFOBT) at ages 60-74. Here, we project the impact of this change on colorectal cancer (CRC) cases and deaths prevented in England by mid-2030. METHODS: We simulated the life-course of English residents reaching age 55 from 2013 onwards. Model inputs included population numbers, invitation rates and CRC incidence and mortality rates. The impact of gFOBT and FS alone on CRC incidence and mortality were derived from published trials, assuming an uptake of 50% for FS and 57% for gFOBT. For FS plus gFOBT, we assumed the gFOBT effect to be 75% of the gFOBT alone impact. RESULTS: By mid-2030, 8.5 million individuals will have been invited for once-only FS screening. Adding FS to gFOBT screening is estimated to prevent an extra 9627 (-10%) cases and 2207 (-12%) deaths by mid-2030. If FS uptake is 38% or 71%, respectively, an extra 7379 (-8%) or 13 689 (-15%) cases and 1691 (-9%) or 3154 (-17%) deaths will be prevented by mid-2030. CONCLUSIONS: Adding once-only FS at age 55 to the NHSBCSP will prevent ∼10,000 CRC cases and ∼2000 CRC deaths by mid-2030 if FS uptake is 50%. In 2030, one cancer was estimated to be prevented per 150 FS screening episodes, and one death prevented per 900 FS screening episodes. The actual reductions will depend on the FS invitation schedule and uptake rates.