Optimizing treatment of brain metastases in an era of novel systemic treatments: a single center consecutive series.

BACKGROUND: The multidisciplinary management of patients with brain metastases consists of surgical resection, radiation treatment and systemic treatment. Tailoring and timing these treatment modalities is challenging. This study presents real-world data from consecutively treated patients and assesses the impact of all treatment strategies and their relation with survival. The aim is to provide new insights to improve multidisciplinary decisions towards individualized treatment strategies in patients with brain metastases. METHODS: A retrospective consecutive cohort study was performed. Patients with brain metastases were included between June 2018 and May 2020. Brain metastases of small cell lung carcinoma were excluded. Overall survival was analyzed in multivariable models. RESULTS: 676 patients were included in the study, 596 (88%) received radiotherapy, 41 (6%) awaited the effect of newly started or switched systemic treatment and 39 (6%) received best supportive care. Overall survival in the stereotactic radiotherapy group was 14 months (IQR 5-32) and 32 months (IQR 11-43) in patients who started or switched systemic treatment and initially did not receive radiotherapy. In patients with brain metastases without options for local or systemic treatment best supportive care was provided, these patients had an overall survival of 0 months (IQR 0-1). Options for systemic treatment, Karnofsky Performance Score ≥ 70 and breast cancer were prognostic for a longer overall survival, while progressive extracranial metastases and whole-brain-radiotherapy were prognostic for shorter overall survival. CONCLUSIONS: Assessing prognosis in light of systemic treatment options is crucial after the diagnosis of brain metastasis for the consideration of radiotherapy versus best supportive care.

Toward omitting sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with clinically node-negative breast cancer.

BACKGROUND: The nodal positivity rate after neoadjuvant chemotherapy (ypN+) in patients with clinically node-negative (cN0) breast cancer is low, especially in those with a pathological complete response of the breast. The aim of this study was to identify characteristics known before surgery that are associated with achieving ypN0 in patients with cN0 disease. These characteristics could be used to select patients in whom sentinel lymph node biopsy may be omitted after neoadjuvant chemotherapy. METHODS: This cohort study included patients with cT1-3 cN0 breast cancer treated with neoadjuvant chemotherapy followed by breast surgery and sentinel node biopsy between 2013 and 2018. cN0 was defined by the absence of suspicious nodes on ultrasound imaging and PET/CT, or absence of tumour cells at fine-needle aspiration. Univariable and multivariable logistic regression analyses were performed to determine predictors of ypN0. RESULTS: Overall, 259 of 303 patients (85.5 per cent) achieved ypN0, with high rates among those with a radiological complete response (rCR) on breast MRI (95·5 per cent). Some 82 per cent of patients with hormone receptor-positive disease, 98 per cent of those with triple-negative breast cancer (TNBC) and all patients with human epidermal growth factor receptor 2 (HER2)-positive disease who had a rCR achieved ypN0. Multivariable regression analysis showed that HER2-positive (odds ratio (OR) 5·77, 95 per cent c.i. 1·91 to 23·13) and TNBC subtype (OR 11·65, 2·86 to 106·89) were associated with ypN0 status. In addition, there was a trend toward ypN0 in patients with a breast rCR (OR 2·39, 0·95 to 6·77). CONCLUSION: The probability of nodal positivity after neoadjuvant chemotherapy was less than 3 per cent in patients with TNBC or HER2-positive disease who achieved a breast rCR on MRI. These patients could be included in trials investigating the omission of sentinel node biopsy after neoadjuvant chemotherapy.

Identifying pathologic complete response of the breast after neoadjuvant systemic therapy with ultrasound guided biopsy to eventually omit surgery: Study design and feasibility of the MICRA trial (Minimally Invasive Complete Response Assessment).

PURPOSE: Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). The MICRA trial (NTR6120) aims at identifying pCR with post-NST biopsies. Here, we report the study design and feasibility. METHODS: The MICRA-trial is a multi-center prospective cohort study. Patients with a pre-NST placed marker and radiologic complete (rCR) or partial response on MRI after NST are eligible for inclusion. Ultrasound guided biopsy of the original tumor area is performed. Pathology results of the biopsies and surgery specimens are compared. The primary endpoint is false-negative rate of biopsies in identifying pCR. RESULTS: During the first year of the trial 58 patients with rCR were included. One patient was a screening failure and excluded for analysis. Twenty-one percent had hormone receptor (HR)+/HER2- tumors, 21% HR+/HER2+ tumors, 18% HR-/HER2+ tumors and 40% TN tumors. Overall pCR was 68%. In seven patients biopsies could not be obtained: in 6 patients, the marker could not be identified on ultrasound in the OR and in 1 patient there were technical difficulties. A median of eight biopsies was obtained (range 4-9). The median of histopathological representative biopsies was 4 (range 1-8). CONCLUSION: Ultrasound guided biopsy of the breast in patients with excellent response on MRI after NST is feasible. Accuracy results of the MICRA trial will be presented after inclusion of 525 patients to determine if ultrasound guided biopsy is an accurate alternative to surgical resection for assessment of pCR after NST.

[Summary of the practice guideline 'Otitis externa' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Otitis externa' (eerste herziening) van het Nederlands Huisartsen Genootschap.

* The practice guideline 'Otitis externa', first developed by the Dutch College of General Practitioners in 1995, has been revised and updated. * It is no longer recommended to perform a KOH test on material collected from the auditory canal in patients with otitis externa. * Eardrops that contain both acid and corticosteroids are preferred over eardrops that contain acid only. * Suitable options include acidic eardrops with hydrocortisone 1% FNA and acidic eardrops with triamcinolone acetonide 0.1% FNA at a dose of 3 drops thrice daily. * The guideline contains a detailed discussion of the ototoxicity of eardrops in patients with tympanic membrane perforation. * Management of these patients, however, remains unchanged: the preferred approach is aluminium acetotartrate eardrops 1.2% FNA.

[Summary of the practice guideline 'Asthma in children' (second revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'astma bij kinderen' (tweede herziening) van het Nederlands Huisartsen Genootschap.

A number of important changes have been made in the second revision of the guideline 'Asthma in children' from the Dutch College of General Practitioners. In children under the age of 6 years, the symptoms stuffiness and recurrent cough are no longer considered part of the symptomatic diagnosis of asthma. Wheezing has become the key symptom of asthma. In children aged 6 years or more, spirometry is the optimal method for both diagnosis and monitoring. This method is preferred over peak flow measurement. Inhalation allergies should be investigated in children under the age of 6 years because the presence of an inhalation allergy may influence the management approach. Starting asthma medication in children under the age of 6 years should always be considered a therapeutic trial, and its effect should always be evaluated. The prescription of allergen-resistant mattresses and bed coverings is only effective when it is one component of a set of allergen reduction measures. At this time, the Dutch Health Council recommends influenza vaccination in children with asthma.

[Summary of the practice guideline 'Children with fever' (Second Revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Kinderen met koorts' (tweede herziening) van het Nederlands Huisartsen Genootschap.

In the second revision of the practice guideline 'Children with fever' from the Dutch College of General Practitioners, due to its greater reliability rectal measurement of the body temperature above measurement with an ear thermometer is recommended in the case of children younger than 3 months, where the classical signs of infectious diseases are often less apparent. The practice guideline distinguishes between alarm signs which can be recognised by the parents and alarm symptoms which can be diagnosed by the physician during a physical examination. In children younger than 2 years who are feverish with no apparent cause, the urine should be examined at the first consultation. An X-ray of the thorax of a child with fever is only necessary if pneumonia is suspected. As it is not possible at an early stage to identify serious cases among children who are feverish without an apparent cause, these children should be re-examined within 24-48 hours. Children with fever who are younger than 3 months should be referred to a paediatrician. A typical febrile seizure is harmless, nevertheless an underlying meningitis should be excluded.

[Summary of the practice guideline 'allergic and non-allergic rhinitis' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Allergische en niet-allergische rhinitis' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The practice guideline 'Allergic and non-allergic rhinitis' of the Dutch College ofGeneral Practitioners has been revised based on developments that have occurred in recent years. The most important modifications are: Impermeable covers for beddings are advised only for patients with serious complaints despite the use of medication and other mite-avoidance measures, and patients with allergic rhinitis with asthma. The indication for the use ofa corticosteroid nasal spray is broadened. There is more evidence for the efficacy ofa nasal spray with antihistamines. The indication for cromoglycate has been restricted. Two major unsolved points of discussion concerned the effectiveness of sublingual immunotherapy and the link between asthma and allergic rhinitis.

[New recommendations as regards forgetting to take the contraceptive pill]. / Nieuwe adviezen bij het vergeten van de anticonceptiepil.

Guidelines from the Dutch College of General Practitioners (NHG), the Scientific Institute of Dutch Pharmacists (WINAp), the Dutch Association for Obstetrics & Gynaecology (NVOG) and the Dutch Expert Centre on Sexuality (Rutgers Nisso Groep) all gave different recommendations on the use of the morning after pill in the event of the contraceptive pill being missed. This is an undesirable situation. Using the 2004 WHO-recommendations on missed pills as a starting point, new Dutch guidelines were drawn up. The consensus is that in the case of only one pill being missed, no extra precautions are necessary. This is by far the most frequent situation. The forgotten pill should be taken as soon as possible. Forgetting to take the pill more than once is a rare occurrence. Iftwo or more pills have been missed, advice will be given in accordance with the existing NHG guideline. The WHO has been requested to initiate research in order to establish if its current recommendations on forgetting more than one contraceptive pill can be supported by better data. The new recommendations will be implemented into harmonized guidelines thus enabling women to be given the same simple advice at every advisory centre.

[Summary of the practice guideline 'Vaginal discharge' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Fluor vaginalis' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The 1996 practice guideline of the Dutch College of General Practitioners (NHG) on vaginal discharge has been updated. Most women who visit their doctor with complaints about vaginal discharge do not have an increased risk of a sexually-transmitted disease. Investigations into vaginal discharge comprise history taking, physical examination and microscopic analysis in the laboratory of the general practitioner. Additional investigation into Chlamydia, gonorrhoea and Trichomonas infection is only necessary if the patient history reveals an increased risk of a sexually-transmitted disease. A Candida infection or bacterial vaginosis should only be treated if the patient experiences bothersome complaints. Treatment of a Candida infection consists of a vaginally applied imidazole compound. Bacterial vaginosis can be treated with oral administration of metronidazole. Patients with vaginal fluor can be examined and, if necessary, treated by their general practitioner. Referral to a gynaecologist is rarely necessary.

[Summary of the practice guideline 'Atopic dermatitis' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Constitutioneel eczeem' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The 1996 practice guideline on atopic dermatitis from the Dutch College of General Practitioners has been updated. For diagnosing atopic dermatitis, the use of Williams' criteria is recommended. Testing for food allergy is only useful in case of children under the age of 2 who have other food-related allergic complaints together with dermatitis. In the treatment of atopic dermatitis, keeping the skin in good condition with emollients is essential; furthermore, topical corticosteroids are the therapy of first choice. In case of a severe exacerbation of atopic dermatitis, starting with a class 3 corticosteroid is preferred. In case of frequent recurrences, 'pulse-therapy' is indicated: topical corticosteroids on 2-4 consecutive days per week as maintenance therapy. The role of preparations from tar is marginal. The use of the topical immunomodulators tacrolimus and pimecrolimus in general practice is discouraged.

[Summary of the practice guideline 'Pelvic inflammatory disease' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Pelvic inflammatory disease' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The 1995 guideline on pelvic inflammatory disease (PID) has been updated. The general practitioner should consider PID whenever a woman of childbearing age complains of lower abdominal pain; the diagnosis should then be based on 5 criteria: (a) non-acute lower abdominal pain; (b) pain on upward movement or adnexal tenderness during vaginal touch; (c) painful or swollen adnexae; (d) ESR > or = 15 mm in the 1st hour or a temperature > 38 degree C, and (e) no indications for other diseases, such as appendicitis or an extra-uterine pregnancy. In case of diagnostic doubt, a gynaecologist must be consulted. Rapid treatment with antibiotics diminishes symptoms, shortens the course of disease, and may prevent complications such as infertility or extra-uterine pregnancy. Treatment should be started with ofloxacin and metronidazole. Due to the increasing antibiotic resistance of Neisseria gonorrhoeae, when there are indications for this pathogen the medicinal treatment should immediately be directed at it by means of cefotaxim, doxycycline and metronidazole. In his or her information to the patient, the general practitioner should devote attention to the major role of sexually transmissible micro-organisms and give advice, if necessary, regarding high-risk behaviour.

[Summary of the practice guideline 'Hearing impairment' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Slechthorendheid' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The Dutch College of General Practitioners recently issued a revised version of the practice guideline 'Hearing impairment'. The modification of the screening for hearing impairment, which now takes place in neonates, has resulted in a much lower number of false-positive diagnoses of perceptive hearing loss than under the previous version of the practice guideline. The expanded diagnostic possibilities for adults, whether or not implemented by the patients themselves, demand an active approach from the general practitioner towards patients with impaired hearing. This guideline helps general practitioners to select patients that will truly benefit from a hearing aid and that will also be more likely to use one. The general practitioner can play an important role by stimulating patients to be referred for a hearing aid.

[Summary of the practice guideline 'Urinary-tract infections' (second revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Urineweginfecties' (tweede herziening) van het Nederlands Huisartsen Genootschap.

The 1999 practice guideline 'Urinary-tract infections' from the Dutch College of General Practitioners has been revised. Not only febrile urinary-tract infections are now regarded as 'complicated', but also all urinary-tract infections in men, pregnant women, children, and patients with kidney or urinary-tract disease, impaired immune response or an indwelling catheter. Under certain conditions, in women recognising the symptoms of an earlier uncomplicated urinary-tract infection, treatment may be instituted without performing supplementary urinalysis. The nitrite dipstick test and dipslide culturing are recommended for the diagnosis of urinary-tract infections; the value of the leukocyte esterase dipstick test is limited. A group-B streptococcal urinary-tract infection during pregnancy is an indication for intravenous antibiotic prophylaxis during the delivery. The recommended duration of treatment with nitrofurantoin is extended from three to five days. Both increased bacterial resistance to trimethoprim and the intention to reduce the use of fluoroquinolones in the treatment of uncomplicated urinary-tract infections were reasons for including phosphomycin in the guideline. In addition to antibiotic prophylaxis, cranberry products may be of value in the prevention of recurrent urinary-tract infections.

[Summary of the practice guideline 'Heart failure' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Hartfalen' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The guideline entitled 'Heart failure' from the Dutch College of General Practitioners has been revised. The general practitioner makes the diagnosis of heart failure in a patient with the core symptoms (dyspnoea, fatigue, oedema) in combination with paroxysmal nocturnal dyspnoea, orthopnoea, crepitations, elevated central-venous pressure, a third heart sound or ifictus cordis is visible outside the mid-clavicular line. Further investigations include a panel of laboratory investigations, an ECG and possibly echocardiography and radiographic chest investigations. One new recommendation is that on suspicion of heart failure the plasma concentrations of B-type natriuretic peptide (BNP) or N-terminal pro-BNP should be investigated. The step-by-step medication plan has been changed; beta-blockers have been introduced to the plan. In the treatment of acute heart failure, rapidly working sublingual nitrates should be given first and foremost.

[Summary of the practice guideline 'TIA' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'TIA' (eerste herziening) van het Nederlands Huisartsen Genootschap.

The new practice guideline of the Dutch College of General Practitioners on the management of patients with a TIA resembles the first version, but there are some important changes: The concept TIA has been narrowed to a neurological deficit that has resolved spontaneously by the time the patient consults the doctor. The indications for referral of patients with a TIA in the area supplied by the carotid artery for investigation of a possible carotid stenosis and carotid surgery have been broadened. Auscultation of the internal carotid artery is no longer necessary. The daily amount of acetylsalicylic acid to be taken by a patient with a TIA has been increased from 30 mg to 80 mg. The prescription of dipyridamol following a TIA remains controversial.

[Summary of the practice guideline 'CVA' from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'CVA' van het Nederlands Huisartsen Genootschap.

The practice guideline 'CVA' from the Dutch College of General Practitioners provides guidelines for the management of stroke patients. The guideline is in agreement with the changing insights about the benefits of stroke-units and thrombolysis. The most important recommendations are the following. In the acute phase, most patients with a cerebrovascular accident should be referred for admission to a stroke-unit. Exceptions are patients with only slight neurological disability and patients with severe comorbidity. Patients with a CVA that started less than three hours ago should be referred for emergency thrombolytic therapy in regions where this possibility exists. In situations in which the general practitioner considers a home visit to involve an unacceptable loss of time, he may decide to refer on the basis of the results of the 'face-arm-speech-time' (FAST) test, which can be administered by telephone. For patients that remain at home, the general practitioner sees to the early start of a rehabilitation programme, and takes the initiative if necessary. The general practitioner can support stroke patients with permanent neurological deficits by considering them to be chronically ill patients requiring regular check-ups.

[Tetanus prophylaxis in general practice]. / Tetanusprofylaxe in de huisartsenpraktijk.

In response to the report 'Immunisation against tetanus following injuries' from the Dutch Health Council, the Dutch College of General Practitioners, the National Coordinating Body for the Control of Infectious Diseases and The Netherlands Vaccine Institute have drawn up guidelines for tetanus prophylaxis in general practice. The number of situations in which the administration of tetanus immunoglobulin or tetanus vaccine is indicated is now considerably lower. Some of the unclear aspects of the report have been further worked out and translated into definite guidelines. The guidelines are not only useful for general practitioners but deserve to be followed by all doctors treating patients with injuries.