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Radiation Safety in Radiation Oncology First Edition K. N. Govinda Rajan
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Preface
The history of radiation therapy for malignant diseases dates back throughout almost the complete twentieth century. Neither three-dimensional crosssectional imaging, such as computed tomography or magnetic resonance imaging, nor functional imaging, such as positron-emission tomography (PET), was available during the frst decades. This resulted in treatment planning approaches that most of today’s radiation oncologists are completely unfamiliar with. One particular example highlighting the development in a highly radio-curable malignancy is Hodgkin’s lymphoma. Compared to historical extended-feld radiotherapy based on bony landmarks defning the feld borders, we have witnessed the introduction of involved feld and involved node radiotherapy, as well as PET-guided or -adapted treatment selection algorithms. Our ability to account for organ motion during treatment delivery has changed the way of administering radiation to the lung and mediastinum. Simultaneously, evolution of image-guided and high-precision application technology has outperformed clinicians’ ability to precisely defne the clinical target volume (CTV) in a number of diseases. Practicing radiation oncologists have to make several important decisions during treatment planning and realization, one patient at a time. It all starts with staging, multidisciplinary discussion, and volume delineation, in case radiotherapy is indicated and recommended. It would be of limited or no value to precisely deliver the prescribed treatment to an incorrectly defned CTV. Artifcial intelligence and deep learning are starting to impact the diagnostic and treatment planning processes and are likely to modify several parts of the present workfow.
The purpose of this book is to provide practicing radiation oncologists and therapists, as well as those in training, with a concise overview of the most important and up-to-date information pertaining to target volume defnition. Several chapters, e.g., those dealing with lymphoma, sarcoma, and spine/spinal cord malignancies, not only include common clinical scenarios but also present challenging cases and rare cancer types. The issue of interobserver variability is addressed, and when available, the reader is introduced to consensus guidelines. The latter have evolved signifcantly after publication of the frst edition of this textbook in 2015. Therefore, a completely updated second edition had to be prepared.
We are most grateful for the enthusiasm and courtesy all chapter authors showed during preparation of this truly international volume and for the fruitful discussion with many colleagues. The SARS-CoV-2 pandemic has
unfortunately delayed the preparation of this second edition. Eventually, all contributors managed to deliver their up-to-date chapters. We also appreciate the excellent long-term support from the publisher. We hope that the reader will fnd this book to be a useful summary of current knowledge. Only continued cooperative research will provide a better basis for tolerable and effcacious treatment regimens, exploiting the promises put forward by the emerging concepts of personalized, ablative, and adaptive radiation therapy.
Freiburg, Germany
Anca-Ligia Grosu Leipzig, Germany Nils Henrik Nicolay Bodø, Norway Carsten Nieder
1 Brain Gliomas of Adulthood
Ilinca Popp, Oliver Oehlke, Carsten Nieder, and Anca-Ligia Grosu
2 Brain Metastases
Carsten Nieder and Laurie E. Gaspar
3 Spinal Cord Tumors
Michael H. Wang, Jay Detsky, Christopher D. Witiw, Ashish Kumar, Mary Jane Lim-Fat, Julia Keith, Pejman Maralani, Simon S. Lo, and Arjun Sahgal
4 Base of the Skull and Orbit 71
Carsten Nieder, Sabrina T. Astner, Tobias Boeckh-Behrens, and Claire Delbridge
5 Head and Neck Cancer
Alexander Rühle and Nils H. Nicolay
6 Lung Cancer
Eleni Gkika, Sonja Adebahr, Tanja Schimek-Jasch, and Ursula Nestle
7 Esophageal Cancer 147
Thomas B. Brunner and Frank Zimmermann
8 Gastric Cancer 177
Francesco Cellini, Calogero Casà, Andrea D’Aviero, and Vincenzo Valentini
9 Pancreatic Cancer
Thomas B. Brunner, Eleni Gkika, and Daniel Schanne
10 Liver Tumours
Eleni Gkika, Daniel Schanne, and Thomas B. Brunner
11 Rectal Cancer
Emmanouil Fokas, Cihan Gani, Vincenzo Valentini, Claus Rödel, and Maria Antonietta Gambacorta
Mark Harrison, Vicky Goh, Ajay Aggarwal, Hendi Maher, Suraiya Dubash, Robert Hughes, and Rob Glynne-Jones
Nina A. Mayr, Larissa J. Lee, William Small Jr, and Catheryn M. Yashar
Robert Förster and Tanja Sprave
Michael S. Rutenberg and Daniel J. Indelicato
Colin E. Champ and Christopher R.
Stefanie Corradini, David Krug, Jan Haussmann, Christiane Matuschek, and Juliane Hörner-Rieber
Alexander Fabian, Justus Domschikowski, Jürgen Dunst, and Oliver J. Ott
Brain Gliomas of Adulthood
Ilinca Popp, Oliver Oehlke, Carsten Nieder, and Anca-Ligia Grosu
I. Popp · O. Oehlke · A.-L. Grosu (*)
Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway
Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
e-mail: Carsten.Nieder@nordlandssykehuset.no
1.1 Introduction
Radiation therapy plays, together with surgery and chemotherapy, a crucial role in the management of malignant brain gliomas. Considering the complex functional anatomy of the brain, in no other anatomical region, the exact delivery of the radiation dose and the protection of normal tissue have such a high impact like in the brain. Therefore, the exact target volume delineation plays an essential role in the high-precision radiation therapy of brain lesions.
A.-L. Grosu et al. (eds.), Target Volume Defnition in Radiation Oncology, https://doi.org/10.1007/978-3-031-45489-9_1
In glioblastoma (GBM), maximum safe surgical resection, conventionally fractionated postoperative radiation therapy over 6 weeks (60 Gy, 2 Gy/day) and chemotherapy with temozolomide (concomitant and sequential to radiotherapy) represent the standard treatment approach (Stupp et al. 2005, 2009). Also, in WHO grade 3 astrocytomas and oligodendrogliomas, radiation therapy plays an important role in the overall treatment strategy, together with chemotherapy with PCV (procarbazine, lomustine, vincristine) or temozolomide (Wick et al. 2009; Cairncross et al. 2013; van den Bent et al. 2013, 2017; Weller et al. 2021). In low-grade gliomas (WHO grade 2), immediate radiation therapy has been shown to result in a progression-free survival beneft and an advantage in seizure control compared with the same treatment given on tumour progression. However, no overall survival beneft was demonstrated (Karim et al. 1996; Shaw et al. 2002, 2012; van den Bent et al. 2005). The decision to perform RT is therefore based on individual risk factors, such as the ones included in the Pignatti score derived from the EORTC trials 22844/22845 (Pignatti et al. 2002). Analogous to the WHO grade 3 tumours, RT is applied followed by sequential chemotherapy with PCV (Buckner et al. 2016; Bell et al. 2020) or temozolomide (van den Bent et al. 2017).
In this chapter, we discuss the target volume delineation for radiation therapy of gliomas in adults considering the recent guidelines of the European Association for Neuro-Oncology (EANO) and the new World Health Organization (WHO) glioma classifcation of 2021 (Weller et al. 2021; Louis et al. 2021). Therefore, we will focus our discussion on low-grade gliomas WHO grade 2 and high-grade gliomas WHO grades 3 and 4. For all these tumour entities, the pathological characteristics and the imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) will be briefy described before the main principals of target volume delineation are individually discussed.
1.2 Epidemiology
The incidence rate of newly diagnosed primary malignant brain tumours is estimated at 3.8 per 100,000 males and 3.1 per 100,000 females per year. This rate is higher in developed countries (males: 5.8 per 100,000; females: 4.4 per 100,000) than in less developed countries (males: 3.2 per 100,000; females: 2.8 per 100,000). About 70% of these tumours are GBM, 10–15% are anaplastic astrocytoma, 10% are anaplastic oligodendroglioma and the rest are less common tumour entities like ependymomas and gangliogliomas (Ferlay et al. 2010; Louis et al. 2007, 2016).
1.3 Pathology
Treatment decisions are based on tissue diagnosis as well as prognostic molecular markers. Therefore, initial surgery is crucial, with both diagnostic and therapeutic intent (Weller et al. 2021).
Gliomas are neuroepithelial tumours and are further classifed by the WHO, complemented by cIMPACT-NOW updates, according to both phenotype and genotype of the cells they arise from (Louis et al. 2016, 2021).
Tumour grading was initially assessed by histopathological features such as the presence of nuclear pleomorphism, increased mitotic activity and cellularity, endothelial cell proliferation and necrosis. With the discovery of new histologic and molecular characteristics of the different glioma entities, the initial classifcation was quickly challenged (Tabatabai et al. 2010; Weller and Wick 2014).
An integrated genomic analysis of GBM led to the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene associated with a signifcant increase in overall survival (Parsons et al. 2008). In a series of 382 patients with WHO grade 3 and 4 gliomas, IDH1 mutation was the most prominent single prognostic
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factor followed by age, histological diagnosis and methylation of the O6-methylguanine-DNA methyltransferase (MGMT) enzyme (Hartmann et al. 2010). Furthermore, based on this mutation, interesting data on the general biology of gliomas could be obtained. By immunostaining autopsyderived human whole-brain sections of four patients with diffuse gliomas using a specifc antibody detecting the R132H mutation of the gene encoding for IDH1 (Capper et al. 2009), it could be demonstrated that gliomas are not only diffusely infltrating into central nervous tissue, but also in fact diseases of the whole brain, bearing tumour cells in macroscopically inconspicuous areas (Sahm et al. 2012).
A further prominent and therapy-relevant characteristic is the epigenetic silencing of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) by promotor methylation in astrocytoma cells. The MGMT methylation predicts responsiveness to temozolomide chemotherapy (Esteller et al. 2000) and is an independent favourable prognostic factor irrespective of treatment (Hegi et al. 2005).
Another common genetic alteration is the codeletion of 1p and 19q (Reifenberger et al. 1994), which is characteristic for oligodendrogliomas (Louis et al. 2016). Two large prospective randomized trials, RTOG 9402 and EORTC 26951, independently showed that loss of 1p/19q was associated with signifcantly longer progression-free and overall survival (Cairncross et al. 2013; van den Bent et al. 2013).
In consequence, the WHO classifcation was adapted in 2016 to include mutational status, e.g. astrocytoma IDH-mutated or wild type and oligodendroglioma IDH-mutated and 1p/19qcodeleted (Louis et al. 2016).
Further identifcation of favourable biomarkers and new drug targets led to the necessity of early revisions and updated recommendations by cIMPACT-NOW (Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) (Rushing 2021). Taking this development into consideration, the most recent WHO classifcation has been published (see Table 1.1), which defnes all IDH wild-type astrocytomas with retained nuclear ATRX as
Table 1.1 Overview of WHO glioma classifcation 2021 (Weller et al. 2021; offcial ref.)
WHO grade Entity
WHO grade 1 Diffuse astrocytoma
Angiocentric glioma
Polymorphous low-grade neuroepithelial tumour of the young (PLNTY)
WHO grade 2 Astrocytoma, IDH-mutant
Oligodendroglioma, IDHmutant and 1p/19q-codeleted
WHO grade 3 Astrocytoma, IDH-mutant
Oligodendroglioma, IDHmutant and 1p/19q-codeleted
WHO grade 4 Astrocytoma, IDH-mutant
Glioblastoma, IDH wild type
Diffuse midline glioma, H3
K27M-mutant
Diffuse hemispheric glioma, H3.3 G34-mutant
Diffuse paediatric high-grade glioma
Characteristics
MYB/MYBL-1-alteration
IDH1 or IDH2 mutation, lack of histologic features of anaplasia, no or low mitotic activity. Absence of microvascular proliferation, necrosis and CDKN2A/B homozygous deletion
IDH1 or IDH2 mutation, deletions of 1p and 19q and absence of anaplasia features
IDH1 or IDH2 mutation, focal or dispersed anaplasia, signifcant mitotic activity. Absence of microvascular proliferation, necrosis and CDKN2A/B homozygous deletion
IDH1 or IDH2 mutation, deletions of 1p and 19q, anaplasia features and/or homozygous CDKN2A deletion
IDH1 or IDH2 mutation. Exhibition of microvascular proliferation, necrosis and/or CDKN2A/B homozygous deletion
With/without MGMT promotor methylation
With/without MGMT promotor methylation
IDH/H3 wild type
GBM, while a nuclear ATRX loss was associated with astrocytic tumours (Weller et al. 2021). IDH-mutated GBMs are now considered IDHmutant astrocytomas, WHO grade 4. In line with the sixth cIMPACT-NOW update, Arabic and not Roman numerals are currently used for grading (Weller et al. 2021; Louis et al. 2021). An overview of the different paediatric- and adult-type gliomas is presented in Table 1.1.
With discoveries of detailed molecular characteristics and subsequently possible drug targets, a thorough tissue management is of high importance for optimal personalized medicine (Jonsson et al. 2019). Individual patient factors, such as tumour localization and histopathologic results, should be considered for selection of adequate nucleic acid tests (FISH, PCR DNA or RNA sequencing). Currently, next-generation sequencing is becoming a common, cost-effective method for multiple gene evaluation (Rushing 2021).
1.4 Imaging
1.4.1 Computed Tomography (CT)
Computed tomography (CT) scans provide specifc geometric details of anatomical structures as well as electron density information for precise dose calculation in treatment planning (Castellano et al. 2021). CT information should be obtained from a contrast-enhanced, 1–2 mm, multi-slice CT, performed from vertex to foramen magnum. Different CT windows (bones, orbit and soft tissue) should be used for the delineation of tumour and critical structures. CT could be an important additional investigation to MRI and PET for visualization of blood/haemorrhagic tissue and soft tissue calcifcation or bone structures. The results of the RTOG (Shaw et al. 2002) and EORTC (Karim et al. 1996; van den Bent et al. 2005) studies on low-grade gliomas, in which the target volume was delineated based on the hypodense area on CT, showed 52–55% progression-free survival 5 years after radiation therapy. The local recurrence was located in the irradiation feld in more than 90% of patients.
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Nevertheless, nowadays, target volume delineation for the treatment of gliomas should no longer exclusively depend on CT imaging (Fiorentino et al. 2013). In rare cases where patients have an absolute or relative contraindication for MRI examination, e.g. pacemaker, insulin or morphine pumps, recently implanted endoprostheses, neurostimulators, cochlear implants and grenade splinters, CT can be used for target volume delineation, alone or ideally together with a PET investigation.
1.4.2
Magnetic Resonance Imaging (MRI)
Due to its outstanding contrast in soft tissue imaging and the availability of axial, sagittal and coronal 3D reconstructable datasets with a slice thickness in the range of 0.5–1.2 mm, pre- and post-operative MRI is the standard imaging modality in glioma target volume delineation and evaluation of treatment response. A standard set of MRI sequences available for glioma target volume delineation should include native and contrast-enhanced 3D-T1-weighted (e.g. MP-RAGE) sequences and thin-sliced 3D-T2weighted sequences (e.g. fuid-attenuated inversion recovery, FLAIR, T2 SPACE).
Generally, low-grade gliomas (WHO grade 2) are hyperintense on T2-weighted and FLAIR images and hypointense on native T1-weighted MRI. Characteristic for low-grade gliomas is the intact blood-brain barrier (BBB), and therefore no contrast enhancement is seen after intravenous application of gadolinium. However, both the T1-weighted images and the T2 sequences have considerable limitations in the precise visualization of the gross tumour volume (GTV), especially in low-grade gliomas with diffuse infltration. Neither on the T1- nor on the T2-weighted images precise differentiation between tumour infltration, oedema, reactive gliosis and other treatment-related changes is possible.
High-grade gliomas (WHO grades 3 and 4) are characterized by contrast enhancement on T1-weighted MRI. Especially GBM shows
areas of necrosis, compression of the surrounding normal tissue and sometimes midline deviation. Tumour-surrounding oedema cannot be differentiated from non-contrast-enhanced tumour areas.
In summary, conventional MRI shows a high sensitivity for the diagnosis of gliomas, but a low specifcity concerning the histology of the tumour tissue. Moreover, traditional MRI is unable to differentiate between tumour and oedema or treatment-related changes. Therefore, the traditional anatomical MRI alone does not offer the information necessary for accurate delineation of tumour margins in brain gliomas.
Advances in MRI can provide signifcant information about the biology of low- and highgrade gliomas and may be used as bio-imaging/ bio-markers for the development of improved treatment strategies. There is data showing that new MRI techniques are able to detect subtle changes in white matter organization (diffusion tensor imaging), cellular proliferation (diffusion MRI and MR spectroscopy) or angiogenesis (perfusion MRI) (Price and Gillard 2011). MR spectroscopy detects various endogenous cellular metabolites. Semiquantitative assessments of metabolite ratios are often used to distinguish low-grade gliomas from high-grade tumours (Castellano et al. 2021). Stadlbauer et al. (2011) used MR spectroscopy for the visualization of the infltration zone of gliomas. In 20 patients, they compared the proton-MRI spectroscopy data with the results of stereotactic biopsies and postulated that the method for automated segmentation of the lesion-related metabolic changes signifcantly improved tumour delineation in brain gliomas compared to traditional methods. Target volume delineation integrating MR spectroscopy imaging abnormalities has been proven feasible (Ken et al. 2013), and an ongoing multicentre phase III trial (SPECTRO-GLIO) is currently comparing standard radiochemotherapy with radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging in newly diagnosed glioblastoma (Laprie et al. 2019).
1.4.3
Positron Emission Tomography (PET)
Although MRI accurately depicts the anatomy of the brain, neither contrast enhancement in T1-weighted images nor hyperintensity in T2-weighted images are specifc surrogates for neoplastic lesions. Moreover, after intensive multimodality treatment of glioma, it has been realized that effects like pseudo-progression or pseudo-remission alter the BBB as well as tumour itself, hereby challenging the predominant role of MRI for visualization of tumour tissue during follow-up (Brandsma et al. 2008).
Mitotically active glioma cells are characterized by increased metabolism (glycolysis, protein synthesis, DNA synthesis; Demetriades et al. 2014). The underlying mechanisms of amino acid PET scans enable a visualization of the increased metabolism in gliomas independent of the BBB integrity (Castellano et al. 2021). Therefore, imaging of biological and molecular tumour characteristics by PET is an emerging approach to improve the visualization of actual tumour extent and for radiotherapy treatment planning (Chen 2007; Weber et al. 2008a, b; Grosu and Weber 2010).
The most widely used PET tracer in oncology is [18F]fuorodeoxyglucose (FDG). In the context of malignant glioma, [18F]FDG-PET was found to be of limited value for GTV delineation, due to the low contrast between healthy brain tissue and tumour (Gross et al. 1998). Amino acid PET has been shown to have a higher sensitivity and specifcity, even in comparison to MRI (Grosu and Weber 2010).
Indeed, target volume delineation of malignant glioma can differ signifcantly between MRI and [11C]methionine (MET)-PET (Grosu et al. 2005a). On the PET/MRI co-registered images, MET uptake on PET and gadolinium enhancement on T1-MRI were detected in all 39 patients (100%). In 5 patients (13%), MET uptake matched exactly with the gadolinium enhancement on T1-MRI. However, in 29 patients (74%), MET uptake was also located outside the gadolinium enhancement on MRI, showing additional
areas of tumour infltration. Moreover, in 27 patients (69%), gadolinium enhancement was also located outside the MET enhancement on PET, showing that gadolinium actually correlates with post-surgery BBB disturbances and not with tumour tissue. Evaluating the hyperintensity area on T2-MRI in comparison to MET uptake on PET, it was observed that the extension of MET uptake was different from the hyperintensity areas. MET uptake was located also outside of the hyperintensity area in 9 of 18 patients (50%), suggesting tumour tissue, and in 100%, the hyperintensity region on T2-weighted MRI extended beyond the MET enhancement area, suggesting post-surgery or tumour-related oedema. These fndings could have a signifcant impact on the development of new recommendations for target volume delineation in gliomas, based on PET.
Lee et al. (2009) evaluated the association between MET uptake on PET and site of failure after radiochemotherapy of GBM. They found that 19/26 patients had a signifcant (>1 cm3) volume delineated by PET (GTV-PET). Five of 19 patients had PET-GTV that was not completely included within the high-dose area, and all the fve showed non-central failures (not located in high-dose area). In the group of patients with adequately covered PET-GTV (14/19), only two developed a non-central treatment failure. The authors concluded that inadequate PET-GTV coverage was associated with increased risk of non-central failure (p < 0.01).
The short half-life of [11C]MET, however, requires the presence of an on-site cyclotron. A tracer with a much longer half-life is [18F] fuoroethyl-l-tyrosine (FET), which has later been shown to equally detect biologically active tumour compared to [11C]MET-PET acquired on the same day (Grosu et al. 2011).
All in all, volumes delineated based on amino acid PET were shown to be discordant in size and location and generally larger than MRI-based volumes (Weber et al. 2008a, b; Niyazi et al. 2011; Lohmann et al. 2019; Galldiks et al. 2021).
Although PET volumes appear to represent the true extent of the tumour and indicate areas of high recurrence risk, the treatment of larger
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lesions may substantially increase acute toxicity. Especially in the case of re-irradiation, the risk–beneft ratio has to be judged carefully.
The impact of PET-based radiation treatment planning on the outcome of patients with recurrent high-grade gliomas treated with fractionated stereotactic radiotherapy was evaluated in a prospective single-institution trial (Grosu et al. 2005b). The median overall survival was 5 months when treatment planning was based on MRI/CT compared with 9 months when target volume was delineated on amino acid PET and MRI/CT (p = 0.03). These data suggest that amino acid PET could indeed have a signifcant impact on patient outcome. The potential clinical beneft of [18F]FET-PET-based target volume delineation compared to MRI for re-irradiation of recurrent GBM is currently under investigation in a prospective multicentre randomized trial GLIAA (NOA10/ARO 2013-01).
1.5 Target Volume Delineation and Radiation Treatment Planning in Gliomas
1.5.1 Low-Grade Gliomas (WHO Grade 2)
Low-grade gliomas WHO grade 2 include, according to the new WHO Classifcation of Tumours of the Central Nervous System (Louis et al. 2016, 2020, 2021), oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and astrocytoma, IDH-mutant. In most grade 2 gliomas, primary treatment modality is surgery, followed by radiotherapy and chemotherapy in most cases. Watch-and-wait strategies are justifed in some asymptomatic younger patients, after histological confrmation. Treatment decisions should generally be at the discretion of a multidisciplinary tumour board.
For radiotherapy target volume delineation, the gross tumour volume (GTV) in low-grade gliomas (oligodendrogliomas and diffuse astrocytomas WHO grade 2) is based generally on hyperintense lesions in T2-weighted and FLAIR MRI images (Table 1.2) (Shaw et al. 2012;
Table 1.2 EORTC and RTOG randomized phase III multicentre studies evaluating the impact of radiotherapy and chemotherapy in low-grade gliomas (WHO grade 2): GTV, CTV and PTV defnition
Trial Irradiation dose GTV
References EORTC 2203326033/ CE5
RTOG 9802
50.4 Gy/1.8 Gy (28 fx) Region of high signal intensity on T2 or FLAIR–MRI corresponding to the hypodense area on CT, including any areas of CT enhancement, or surgical cavity + any residual tumour
54 Gy/1.8 Gy (30 fx)
T2 or FLAIR MRI-defned tumour volume
Not defned see PTV
Fairchild et al. (2012), Musat et al. (2010), Baumert et al. (2016)
1 cma Shaw et al. (2012), Buckner et al. (2016)
a The treatment felds included the T2 or FLAIR MRI-defned tumour volume plus a 2 cm margin to block edge, resulting in an approximate 1 cm dosimetric margin
Fairchild et al. 2012; Musat et al. 2010), considering that an important characteristic of these tumours is the absence of contrast enhancement on T1-weighted MRIs. However, it is well known that the sensitivity of T2 and FLAIR MRI for tumour tissue is very high, but the specifcity is relatively low. Thus, tumour tissue cannot be differentiated from surrounding oedema or treatment-related changes (for example, tissue injury after surgery). Therefore, the problem remains that in non-operated low-grade gliomas, the GTV delineated based on T2-weighted and/or FLAIR MRI could encompass not only tumour tissue but also oedematous normal brain tissue (Fig. 1.1). Additionally, in operated patients, the GTV could include, close to residual tumour, non-tumoural tissue with hyperintense signal on T2 and FLAIR, e.g. post-surgery gliosis and oedema. After complete tumour resection, the concept of GTV encompassing the resection cavity—as used generally in different trials and publications—is not in line with the ICRU criteria for GTV defnition: the resection cavity should be included in the clinical target volume (CTV) and not in the GTV defnition.
The CTV encompasses the possible microscopic tumour infltration, including the resection cavity (in operated patients) and the surrounding normal-appearing tissue in an area of 5–15 mm, excluding anatomical borders like falx, skull and liquor areas (Fairchild et al. 2012). One can make the distinction between well-delineated low-grade gliomas, in which the margins from GTV to CTV can be small (ca. 5 mm, similar to the margins defned in radiosur-
gery/stereotactic treatment—Gagliardi et al. 2021) and diffuse infltrative low-grade gliomas, in which the distance from GTV to CTV should be larger (ca. 10–15 mm), considering anatomical borders.
Based on the results of the EORTC 2203326033 trial, Dirven et al. showed that the brain target volume receiving focal radiation therapy to a total dose of 50.4 Gy in daily fractions of 1.8 Gy did not appear to be independently associated with health-related quality of life (HRQoL) in high-risk patients with low-grade glioma over the frst 24 months after treatment, as opposed to tumour progression. However, the impact of radiation volumes on long-term HRQoL, as well as neurocognitive functioning, remains to be evaluated in future studies.
We generally recommend the co-registration of pre- and post-surgery MRI/CT images. The pre-surgery GTV can contribute signifcant information about the possible microscopic tumour infltration (CTV). However, in this case, the possible changes of the brain anatomy after surgery should be taken into consideration.
The planning target volume (PTV) should be defned considering the precision of patient positioning in each institution. In low-grade gliomas, high-precision radiation therapy is mandatory. Stereotactic techniques and/or image-guided radiotherapy are needed to reduce the distance between CTV and PTV to 1–3 mm.
Summarizing, the target volume delineation for high-precision radiation therapy in low-grade gliomas is based on T2-weighted and FLAIR MRI. Because of the relatively low specifcity of
Fig. 1.1 Astrocytoma WHO grade 2 in a 52-year-old female patient treated with stereotactic fractionated radiotherapy. This is a particular example of a brainstem tumour located in the medulla oblongata, for which special consideration of normal tissue dose constraints is warranted. In order to ensure both treatment effcacy and tolerability, the total dose was set to 45 Gy in 1.8 Gy fractions, with a sequential 9 Gy boost in 1.8 Gy fractions to the metabolically active region. The GTV (yellow) was delineated based on the T1/T2-MRI image fusion (a, b).
these MRI sequences for tumour tissue, new imaging methods for a higher precision in GTV delineation are needed.
For radiation treatment planning, intensitymodulated radiotherapy (IMRT) combined with stereotactic radiotherapy (SRT) and/or imageguided radiotherapy (IGRT) should be considered. Multiple felds including vertex felds or combined dynamic arcs should be used to achieve a high conformity index. However, the dose to thyroid gland, spinal cord and total body should be minimized (Fairchild et al. 2012). Further special consideration should be given to protection of the hippocampi, as cognition and quality of life play an important role in long-term survivors (Acharya et al. 2019). The neurocognitive areas mostly altered by irradiation are verbal- and nonverbal memory, executive function, sustained attention and processing speed (McDuff et al. 2013; Saury and Emanuelson 2011; Makale et al. 2017). In low-grade gliomas, equivalent dose in 2 Gy fractions (EQD2 α/β = 2 Gy) to 40% of the hippocampi (D40%) should not exceed 7.3 Gy, as this dose is associated with long-term neurocognitive impairment in list-learning delayed verbal recall (Gondi et al. 2012). This fnding could not be reproduced in a study on 29 patients with lowgrade glioma having received a D40% of 47.2 EQD2 Gy (Jaspers et al. 2019). In the attempt to derive dose constraints for the hippocampi for radiotherapy of benign or low-grade gliomas in children and young adults, a single-institution prospective trial proposed a mean dose ≤30 Gy to the left hippocampus as a dose constraint to prevent IQ decline and long-term neurocognitive impairment (Goda et al. 2020).
The GTV for the boost (GTV boost, red) was delineated based on FET-PET (c). The CTV was defned as 3 mm margin from GTV, considering the anatomical borders, and the PTV was defned as CTV plus 2 mm. The PTV boost was defned as the GTV boost with 5 mm margins, but also including the MRI-based GTV. (d) Shows the dose distribution in the PTV (light pink) and PTV-boost region (dark pink). The images below (e, f) show the T2 and T1-MRI 4 years after treatment, showing partial tumour remission
The total dose recommended in low-grade gliomas ranges between 50.4 and 54 Gy (Fairchild et al. 2012; Shaw et al. 2012) in 28–30 fractions of 1.8 Gy/day, 5 days/week (Castellano et al. 2021). Long-term follow-up from a recent phase III randomized trial suggested no beneft from high-dose (64.8 Gy in 36 fractions) over lowdose irradiation (50.4 Gy in 28 fractions) of lowgrade gliomas with respect to overall survival and progression-free survival (Breen et al. 2020). It is, however, important to mention that, beginning with the 2021 WHO classifcation, IDH wildtype astrocytomas are considered GBM, irrespective of histopathological grading (see Table 1.1). Therefore, previously diagnosed lowgrade IDH wild-type astrocytomas are now to be treated with 60 Gy in 30 fractions with concomitant chemotherapy following the STUPP protocol.
1.5.2 High-Grade Gliomas (WHO Grade 3)
WHO grade 3 gliomas include oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and astrocytoma, IDH-mutant WHO grade 3 (Louis et al. 2016, 2020, 2021).
Describing target volume delineation for WHO grade 3 gliomas according to the previous WHO classifcations, Whitfeld et al. (2014) mentioned two radiological patterns of such tumours:
1. WHO grade 3 gliomas that have the radiological characteristics of GBM. These might best
be treated based on T1-MRI with gadolinium (see Sect. 5.3).
2. WHO grade 3 gliomas with low or lack of contrast enhancement on T1-MRI. In these tumours, the GTV should encompass the T1-MRI with gadolinium plus the hyperintensity area on T2/FLAIR. The CTV should include the GTV plus 1.0–1.5 cm.
Even if, as the authors comment, there is no hard evidence for this strategy, it is well supported by clinical experience. While these two patterns correlate to some extent with prognostic factors, such as the IDH mutation or the 1p19q codeletion, there is still variability within molecular groups (Juratli et al. 2019).
In aggressive, GBM-like high-grade gliomas (following the frst pattern described above), recurrences occur in more than 90% in the contrast enhancement area. In a signifcant number of patients, hyperintensity on T2 is caused by oedema, and oedema is a consequence of tumour compression and not of macroscopic tumour invasion (see amino acid PET data, Sect. 4.3).
Therefore, T1-MRI and not T2/FLAIR should be used for GTV delineation. On the other side, in WHO grade 3 gliomas, following the second radiological pattern and often arising from previous low-grade gliomas, the regional malignant transformation in small islands is a frequent pathological characteristic. In this case, oedema caused by tumour compression is smaller or absent. Therefore, the T2/FLAIR sequences should be included in target volume delineation because changes in T2/FLAIR are related to tumour invasion. This concept was generally followed also by the EORTC and RTOG clinical trials, as presented in Table 1.3.
In our opinion, we have to keep in mind that, fortunately, the prognosis in a signifcant number of these patients might be favourable. Therefore, we have to put a lot of effort in sparing normal brain tissue to avoid late side effects after radiotherapy. We recommend using additional information from amino acid PET (if available) and pre-surgery MRI/CT for GTV and CTV delineation (Fig. 1.2). Anatomical borders should also be considered. Stereotactic fxation and image-
guided radiotherapy could help to reduce the distance from CTV to PTV to 1–2 mm.
The total dose should be 59.4 (60) Gy in 1.8 (2.0) Gy/day, 5×/week. The delivery of a lower dose (45–50.4 Gy) to a larger PTV (based on T2-MRI/FLAIR) and a higher dose to the boost region (based on GdT1-MRI) in large, multicentric tumours is a good concept, sparing more normal brain tissue (Table 1.3).
1.5.3 High-Grade Gliomas (WHO Grade 4)
The group of gliomas WHO grade 4 includes astrocytoma, IDH-mutant WHO grade 4; glioblastoma (GBM) IDH wild type; diffuse hemispheric glioma, H3.3 G34-mutant; and diffuse midline glioma, H3 K27M-mutant (Louis et al. 2016, 2020, 2021).
In GBM, a GTV-to-CTV margin of 2 cm has been the standard (Hochberg and Pruitt 1980; Wallner et al. 1989; Niyazi et al. 2016). The 2021 newly defned category of WHO grade 4 astrocytoma corresponds to the entity previously known as IDH-mutated GBM. Therefore, its treatment remains at the moment identical to the one of GBM, as per extrapolation.
It should be noted that despite the local treatment approach, diffuse gliomas represent a systemic brain disease upon diagnosis (Sahm et al. 2012). This fact might explain the limited if any role of dose escalation beyond 60 Gy, which was demonstrated in numerous studies. However, the impact of dose escalation might become clinically apparent if clear defnition of a biologically relevant subvolume or molecular disease feature allows for targeted dose escalation to the right volume in the right patient (Nieder and Mehta 2011).
In GBM, T2/FLAIR sequences often show oedema surrounding the tumour, suspicious of subclinical tumour cell infltration. However, for GBM, it has been shown that inclusion of this oedema in the GTV leads to signifcantly larger irradiation volumes and doses to the whole brain compared to a standard GTV-to-CTV margin of 2 cm without inclusion of oedema but does not
I. Popp
Table 1 .3 EORTC and RTOG randomized phase III multicentre studies evaluating the impact of radiotherapy and chemotherapy in high-grade gliomas (WHO grade 3): GTV,
References
Cairncross et al. ( 2013 )
CTV and PTV defnition
Van den Bent et al. ( 2013 )
van den Bent et al. ( 2017 ), Abrunhosa- Branquinho et al. ( 2018 )
Wick et al. ( 2009 , 2016 )
GTV
GTV + 2 cm
Boost: GTV + 1 cm
Not defned (considered in PTV)
Surgical cavity and T2 abnormality
GTV + 2 cm
Boost: T1 abnormality + 1 cm
Not defned (considered in PTV)
Contrast enhancement on T1, T2 abnormality
PTV-1:
GTV + 2.5 cm
PTV-2:
Not defned (considered in PTV)
Low-density area on preoperative CT and/or the hyperintensity area on preoperative T2-MRI
Fig. 1.2 Forty-Year old female patient with an IDHmutated WHO grade 3 astrocytoma treated with 59.4 Gy in 1.8 Gy fractions (applied to PTV, pink). Patient was known to have deteriorating vision prior and not related to diagnosis. For maximal protection of the optical structures, a simultaneous integrated protection with 56.10 Gy in 1.7 Gy fractions (SIP, blue contour) was applied to the intersection of the PTV with a 3 mm expansion of the chiasma and optical nerves (Brunner et al. 2016). The preop-
alter the central pattern of failure (Chang et al. 2007). Therefore, contrast-enhanced T1-MRI sequences should be the basis for GTV delineation in GBM (Fig. 1.3). If perifocal oedema is incorporated into the initial GTV, a 1 cm expansion should be suffcient (Lo et al. 2013). Excluding peritumoral oedema may permit a signifcant reduction of irradiated brain volume, but safety, effcacy as well as reduction in treatmentrelated neurotoxicity have not been demonstrated in prospective, randomized trials, yet (Minniti et al. 2010). Different strategies for target volume delineation in GBM have been considered standard across the world (Niyazi et al. 2016) and are presented in Table 1.4.
erative FLAIR-MRI (a, GTV-preOP, orange), post-operative contrast-enhanced T1-MRI (b, GTVpostOP, green) and post-operative FLAIR-MRI (c) were used for treatment volume delineation. The CTV was defned as a 1.5 cm margin from GTV, considering the anatomical borders, and the PTV was defned as CTV plus 2 mm. Post-operative FET-PET was negative in this patient. (d–f) Shows the dose distribution with protection of the optical structures
Several retrospective studies have investigated the impact of smaller GTV-to-CTV margins (5 mm–1.5 cm) and have found that the pattern of GBM failure suffers only little change as compared to larger margins (Gebhardt et al. 2014; Paulsson et al. 2014; Navarria et al. 2018; Guram et al. 2019). Over 80% of patients still experience in-feld recurrence, while the number of marginal failures remains low, with no apparent difference in survival. Taking into consideration that reduced margins were also successfully used in the prospective trial by Perry et al. (2017), the international consensus tends to lean into reducing the standard margins from 2 cm to 1.5 cm.
I. Popp et al.
Fig. 1.3 Forty-four-Year-old male patient with GBM. Preoperative contrast-enhanced T1- (a) and FLAIR-MRI (b), planning CT (c) and post-operative contrast-enhanced T1- (d) and FLAIR-MRI (e) sequences were used for target volume delineation. The CTV was
defned as a 1.5 cm margin from GTV (green), considering the anatomical borders and including the FLAIRpositive areas (light blue). The PTV (pink) was defned as CTV plus 2–3 mm. (f) Presents the corresponding radiotherapy treatment plan
Table 1.4 EORTC and RTOG randomized phase III multicentre studies evaluating the impact of radiotherapy and chemotherapy in glioblastoma (GBM, WHO grade 4): GTV, CTV and PTV defnition
Like in other gliomas, amino acid PET and pre-surgery MRI/CT should be co-registered with the planning imaging and considered in the GTV and CTV delineation.
Generally, GBMs/grade 4 gliomas are treated with a total dose of 60 Gy, 2 Gy/day, 5×/week. In elderly or frail patients, hypofractionation with 40 Gy in 15 daily fractions of 2.67 Gy could reduce the treatment time without signifcant side effects (Roa et al. 2004; Minniti et al. 2013; Perry et al. 2017).
1.5.4 Future Perspective: Recurrence Pattern Analysis and Risk-Adapted, Automated Target Volume Delineation, Protons and Carbon Ions
In the past years, there has been a considerable increase in the medical use of machine learning. Automatizing organ at risk and GTV delineation has been the main focus (Ermiş et al. 2020). Convolutional neural networks are trained to differentiate different types of tissue on MRI using previously manually delineated volumes and thus to automatically segment organs, resection cavities and tumour lesions. Segmentation results are then validated on larger cohorts. This development can signifcantly speed up the contouring process. Moreover, the extraction of radiomic features and the construction of a tumour mapping through the use of convolutional neural networks (CNN) will play in the future a signifcant role in understanding the morphology and biology of gliomas (Calabrese et al. 2022; Carles et al. 2021; Franco et al. 2021).
Furthermore, there are emerging approaches for the automatic delineation of the CTV. Taking into consideration that the CTV is defned only on the assumption of tumour cells and is highly based on clinical experience and previous knowledge of tumour cell spread, the delineation of the CTV may be considered as the weakest link in the treatment planning chain. Automation of CTV delineation has therefore been proposed to
signifcantly reduce inter-observer variability and improve consistency (Shusharina et al. 2020). Moreover, by analysing recurrence patterns, a risk-adapted, highly individualized CTV delineation appears possible and may represent an important option in the future.
For example, MGMT-methylated tumours are associated with better local control, yet more frequent distant failure compared to those tumours without methylation (Minniti et al. 2010). Further studies are necessary to investigate whether a CTV adaption based on MGMT status may be reasonable (Lo et al. 2013). It is also assumed that regions of GBM stem cell niches are responsible for tumour recurrence and hence must be eradicated in order to prevent recurrence. Noninvasive identifcation and subsequently incorporation of those cancer stem cell niches into the CTV might improve overall survival in patients with GBM (Lo et al. 2013).
Despite the higher protection of the normal brain tissue using protons and/or carbon ions, there are no convincing clinical data showing a higher impact in comparison to IMRT/IGRT photon radiation therapy. The role of protons and carbon ions in the treatment of gliomas is under investigation (Combs 2018).
1.5.5 Recurrent Gliomas
In recurrent gliomas, defnitive treatment procedures have not yet been established. Summarizing the data from the literature about re-irradiation in high-grade gliomas, we found a signifcant number of studies (14 included in a previous review) evaluating 300 patients with GBM. Sixmonth progression-free survival rate was 28–39%, 1-year survival rate was 18–48% without additional chemotherapy (two studies: topotecan and CCNU) and median value for 1-year survival rate was 26% (Nieder et al. 2008). These are encouraging results considering the relatively low rate of serious side effects if the total re-irradiation dose remains lower than 30–40 Gy in 2–5 Gy/fraction (Mayer and Sminia 2008).
I. Popp et al.
However, systematic randomized trials are needed to fully elucidate the role of re-irradiation. Data from Grosu et al. (2005a, b) and level III recommendations from Ryu et al. (2014) have confrmed that re-irradiation can be safely given for progressive GBM. The re-irradiated volume should be limited to the absolute mandatory to avoid possible neurotoxicity (Castellano et al. 2021). Generally, the GTV encompasses the contrast enhancement on contrast-enhanced T1-MRI with a small margin of 3–5 mm to CTV. Re-irradiation should be performed using high-precision radiation therapy (stereotactic radiotherapy, IMRT, IGRT). Therefore, the typical distance from CTV to PTV is small, e.g. 1–3 mm (see also Sect. 4.3) (Grosu et al. 2005b). GTVs delineated on PET and MRI may often differ with respect to size and even location (e.g. Fig. 1.4). Whether a [18F]FET-PET-based target volume delineation is benefcial compared to MRI for re-irradiation of recurrent GBM is cur-
rently under investigation in the prospective multicentre randomized trial GLIAA (NOA10/ ARO 2013-01) (Oehlke et al. 2016).
1.5.6 Organs at Risk
The organs at risk that should also be delineated include eyes, lenses, optic nerves, optic chiasm, inner ears, brainstem, pituitary gland and hypothalamus. Additionally, the volume of the whole brain should be contoured to be able to evaluate the mean brain dose. Many centres also delineate the hippocampi to estimate the risk of neurocognitive decline and to be able to spare these structures as much as possible by using IMRT, if applicable (Table 1.5) (Niyazi et al. 2016).
Constraints for re-irradiation of recurrent gliomas could be extrapolated from the ones used in the ongoing GLIAA trial (Oehlke et al. 2016) (Table 1.6).
Fig. 1.4 Sixty-four-Year-old male patient with recurrent GBM in the right temporal lobe. Left: coronal contrastenhanced T1-weighted MRI and right: coronal FET-PET image. Green contour: GTV delineated based on
MRI. Red contour: GTV delineated based on FET-PET, showing active tumour tissue beyond the MRI contrastenhancing lesion, in otherwise inconspicuous MRI region
Table 1.5 Tolerance doses for intracranial organs
Organ
Brain 1/3
2/3
3/3
1/3
Optic nerves and chiasm
1/3
2/3
3/3
Brainstem
TD5/5: 60 Gy
TD50/5: 75 Gy
TD5/5: 50 Gy
TD50/5: 65 Gy n.a.
TD5/5: 45 Gy
TD50/5: 60 Gy n.a.
TD5/5: 72 Gy n.a.
TD5/5: 50 Gy
TD50/5: 65 Gy n.a.
TD5/5: 50 Gy
TD50/5: 65 Gy n.a.
TD5/5: 50 Gy
TD50/5: 65 Gy
<1 mL 55 Gy n.a.
1/3
2/3
3/3
Retinae 1/3
2/3
3/3
Lenses 1/3
2/3
3/3
TD5/5: 60 Gy
TD50/5: 75 Gy n.a.
TD5/5: 53 Gy
TD50/5: 70 Gy n.a.
TD5/5: 50 Gy
TD50/5: 65 Gy n.a.
TD5/5: 45 Gy
TD50/5: 65 Gy n.a.
TD5/5: 45 Gy
TD50/5: 65 Gy n.a.
TD5/5: 45 Gy
Necrosis, infarction Emami et al. (1991)
Necrosis, infarction
Necrosis, infarction
Necrosis, infarction Lawrence et al. (2010)
Visual impairment Emami et al. (1991)
Visual impairment
Visual impairment
Visual
Neuropathy
Mayo et al. (2010)
Daly et al. (2007)
Neuropathy Schoenfeld et al. (2008)
Neuropathy Emami et al. (1991)
Neuropathy
Neuropathy
Blindness Emami et al. (1991)
Blindness
TD50/5: 65 Gy n.a. Blindness
TD5/5: 10 Gy
TD50/5: 18 Gy n.a. Cataract
TD5/5: 10 Gy
TD50/5: 18 Gy n.a. Cataract
TD5/5: 10 Gy
TD50/5: 18 Gy n.a. Cataract
Table 1.6 Tolerance doses for intracranial organs in case of re-irradiation (analogous to the GLIAA trial, Oehlke et al. 2016)
Organ Parameter Maximum cumulative dose (EQD2 α/β = 2)
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Brain Metastases
Carsten Nieder and Laurie E. Gaspar
2.4
C. Nieder (*)
Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodø, Norway
Department of Clinical Medicine, Faculty of Health Sciences, UiT—The Arctic University of Norway, Tromsø, Norway
e-mail: carsten.nieder@nlsh.no
L. E. Gaspar
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA
Banner MD Anderson Cancer Centers of Northern Colorado, Greeley, CO, USA
e-mail: laurie.gaspar@cuanschutz.edu
Introduction
Despite vastly improved approaches to reduce microscopic dissemination of cancer cells and development of anticancer drugs that pass through the blood-brain barrier, the development of brain and leptomeningeal metastases continues to shorten the life of many cancer patients worldwide and has the potential to cause dramatic consequences for independent functioning and quality of life (Nolan and Deangelis 2018). Both neurologic and cognitive decline may result from the uncontrolled growth of metastatic brain
A.-L. Grosu et al. (eds.), Target Volume Defnition in Radiation Oncology, https://doi.org/10.1007/978-3-031-45489-9_2
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CHAPTER III.
F watched the opening of the farmhouse door with dread, as there peeped out a man’s face, pale, flat, puffy, with light eyes and colourless light eyelashes. Freda took an instantaneous dislike to him, and tried to draw her companion back by the sleeve.
“What do you want at this time of night?” asked, the man pompously.
And Freda knew, by his speech and manner, that he was a manservant, and that he was not a Yorkshireman. He now opened the door wider, and she saw that he was dressed in very shabby livery, that he was short and stout, and that a lady was standing in the narrow entrance-hall behind him. Barnabas caught sight of her too, and he hailed her without ceremony.
“Hey theer, missus,” he cried cheerily, “can Ah have a word with ’ee?”
Rather under than above the middle height, dressed plainly in a black silk gown, Mrs. Heritage was a woman who had been very pretty, and who would have been so still but for a certain discontented, worried look, which seemed to have eaten untimely furrows into her handsome features.
“Well, Mr. Ugthorpe, and what do you want?”
“Here’s a young gentlewoman without a shelter for her head, an’ Ah thowt ye would be t’ person to give it her.”
“Young gentlewoman—without shelter!” echoed the lady in slow, solemn, strident tones. “Why, how’s that?”
“I was snowed up in the train, madam, on my way to my father’s. And we are very sorry to have troubled you. Good-night.”
Very proudly the girl uttered these last words, in the high, tremulous tones that tell of tears not far off. While Barnabas stopped at the door to argue and explain, Freda was hopping back through the snow towards the lane as fast as she could, with bitter mortification in her heart, and a weary numbness creeping through her limbs.
Suddenly through the night air there rang a cry in a deep, full, man’s voice, a voice that thrilled Freda to the heart, calling to something within her, stirring her blood.
“Aunt, she’s lame! Don’t you see she’s lame?”
She heard rapid footsteps in the snow. As she turned to see who it was that was pursuing her, and at the same time raised her hand to dash away the rising tears and clear her sight, her little crutch fell. She stooped to grope in the snow, and instantly felt a pair of strong arms around her. Not Barnabas Ugthorpe’s. There was no impetuous acting upon impulse about Barnabas. And in the pressure of these unknown arms there seemed to Freda to be a kindly, protecting warmth and comfort such as she had never felt before.
“Who is it? Who are you?” she cried tremulously.
“Never mind, I’ve been sent to take care of you,” answered the voice.
Again it thrilled Freda; and she was silent, rather frightened. She gave one feeble struggle, seeing nothing through her tears in the darkness, and her ungloved hand touched a man’s moustache. To the convent-bred girl this seemed a shocking accident: she was dumb from that moment with shame and confusion. The goodhumoured remonstrance of the unseen one caused her the keenest anguish.
“Oh, you ungrateful little thing. You’ve scratched my face most horribly, and I don’t believe there’s a bit of sticking-plaster in the house. Next time I shall leave you to sleep in the snow.”
“I—I am sorry. I beg your pardon,” she faltered. “I did not see.”
“All right. I’ll forgive you this once. Not that I think you’ve apologised half enough.”
At first she took this as a serious reproach, and wondered what she could say to soothe his wounded feelings. But the next moment, being quick-witted, she began dimly to understand that she was being laughed at, and she resolved to hold her peace until she could see the face of this creature, who was evidently of a kind quite new to her experience, with puzzling manners and a way of looking at things which was not that of the nuns of the Sacred Heart.
In a few moments Freda heard the voice of Barnabas thanking Mrs. Heritage for her good cheer as he came out of the house. Then
she found herself put gently down on her feet inside the doorway, while she heard the strident tones of the lady of the house, asking her not unkindly whether she was wet and cold. But even her kindness grated on Freda; it was hard, perfunctory, she thought. There was all the time, behind the thoughtful hospitality for her unexpected guest, some black care sitting, engrossing the best of her. Mrs. Heritage hurried on, through a labyrinth of rooms and passages, to an oaken door, old and worm-eaten, studded with rusty nails.
“This room,” she said, turning back as the door rolled slowly inwards, “is the one wreck of decent life on which we pride ourselves. It is the old banqueting-hall of the castle. We took it into use, after an hundred and fifty years’ neglect, when we were obliged to come and bury ourselves here.”
It was a long and lofty room with a roof of oak so ancient that many of the beams were eaten away by age. The walls were of rough stone, hung, to a height of six feet from the ground, with worn tapestry, neatly patched and mended. The hall was lighted by six Gothic windows on each side, all of them ten feet from the ground. The furniture, of shabby and worm-eaten oak, consisted chiefly of a number of presses and settles, quaintly shaped and heavy-looking, which lined the walls. On one end of a long table in the middle, supper was spread, while at the further end of the hall a log-fire burned in a large open fireplace.
“Where is Richard?” asked Mrs. Heritage solemnly, just as the door was pushed open, and three or four dogs bounded in, followed by a tall young man in knickerbockers and a Norfolk jacket, with a dog-whip sticking out of his pocket. It was Freda’s unknown friend.
“Let me introduce you,” said his aunt. “My nephew, Mr. Richard Heritage to—— What is your name, child?”
Freda hesitated. Then, with the blood surging in her head, she answered in a clear voice:
“Freda Mulgrave.”
She had expected to give them a surprise; but she had not reckoned upon giving such a shock to Mrs. Heritage as the announcement plainly caused her. Dick, whose careless glance had,
for some reason which she did not understand, pained her, at once turned to her with interest.
“You know my father. What is he like?” she ventured presently, in a timid voice, to Mrs. Heritage, when she had explained how she came to be travelling alone to Presterby.
“He is a tall, dignified-looking gentleman, my dear, with a silvergrey beard and handsome eyes.”
“And does he live all by himself?”
“I believe his establishment consists of a housekeeper, and her husband, who was one of his crew.”
“And decidedly a rough-looking customer, as you will say when you see him, Miss Mulgrave,” chimed in Dick. “This Crispin Bean, who belonged to Captain Mulgrave’s ship at the time of the—the little difficulty which ended in his withdrawing from the Navy, has followed him like a dog ever since. It’s no ordinary man who can inspire such enthusiasm as that,” he went on, as he stood by the big fireplace, and kicked one of the burning logs into a fresh blaze. “You must have noticed,” he said presently, “that the discovery of your being your father’s daughter had some special interest for us?”
“Yes, I did think so,” said Freda.
“You see,” Dick went on, pulling his moustache and twisting up the ends ferociously, “we’re very poor, poor as rats. It’s Free Trade has done it. We—my cousin and I—have to farm our own land; and as we can’t afford the railway rates, we sell what we produce to our neighbours. If they left off buying we couldn’t live. Well, my cousin and your father have had a quarrel, and we’re afraid Captain Mulgrave won’t buy of us any more. You understand, don’t you?”
“Oh, yes,” said Freda slowly, struggling with her sleepy senses. “He has quarrelled with your cousin, and so you’re afraid he’ll buy what he wants not from you but from Josiah Kemm.”
Both her hearers started violently, and Freda perceived that she had let out something he had not known.
“I stayed for an hour at an inn called the ‘Barley Mow,’ ” she explained, “and I heard something there which I think must have had some meaning like that. But perhaps I am wrong. I am tired, confused—I——”
Her voice grew faint and drowsy. Dick glanced at Mrs. Heritage.
“Don’t trouble your head about it to-night,” said he. “You are tired. Aunt, take Miss Mulgrave to her room. Good-night.”
And poor Freda, sleepy, contrite, was hurried off to bed.
Next morning she was down early, but she saw nothing of Dick. The mistress of the house read prayers in a tone of command rather than of supplication; and, as the servants filed out afterwards, she called the butler, and asked:
“What is this I hear about Master Richard’s going off on ‘Roan Mary’ at this time in the morning?”
“It’s a telegram he wants to send to Master Robert; and he has to ride to Pickering because the snow’s broken down the wires on this side,” answered Blewitt sullenly. “I saw the message. It said: ‘He is on with Kemm. Call on your way back.’ ”
Freda caught the name “Kemm.” She felt very uncomfortable, but nobody noticed her, and she was suddenly startled by an outbreak of sobs and moans from Mrs. Heritage, who had begun to pace up and down the room.
“That’ll do,” said Blewitt sullenly, “I’m going to have a talk with you, ma’am. We’d best have things square before your precious son Robert comes back. I want to know when I’m to have my wages. I don’t mean my thirty-five pounds a year for waiting at table, but the wages I was promised for more important work.”
“I will speak to Mr. Robert as soon as he returns, Blewitt,” said Mrs. Heritage, who was evidently in a paroxysm of terror. “I am quite sure——”
“That I shall get no good out of him,” went on Blewitt, doggedly. “Do you think I don’t know Mr. Robert? Why, miss,” and the man turned, with a sudden change of manner to deprecating respect, to Freda, “your father, Captain Mulgrave, knows what Mr. Robert is, and that’s why he’s made up his mind, like the wise gentleman he is, not to have anything more to do with him. And I’ve made up my mind,” he went on with vicious emphasis, heeding neither Mrs. Heritage’s spasmodic attempts to silence him, nor the young girl’s timid remonstrances, “either to have my due or to follow his example.”
Freda had crept up, with her little crutch, to Mrs. Heritage’s side, and was offering the mute comfort of a sympathetic hand thrust into
that of the lady
“Run away, my dear child, run away,” whispered the latter eagerly.
The man went on in a brutal tone:
“I’m not such a fool as Master Dick, to stay here and be made a catspaw of, while your precious son goes off to enjoy himself. Why should some do all the work, and others——”
The rest of his sentence was lost to Freda, who had got outside the door into a great bare apartment beyond. Here, lifting the latch of a little modern door which most inappropriately filled an old Gothic doorway, she found herself, as she had expected, in the courtyard.
CHAPTER IV.
F crossed the courtyard to one of the ruined corner-towers, and finding the staircase still practicable, continued her wanderings, with cautious steps, along the top of the broken castle-wall. She got along easily as far as the thatched roof of a big barn. But here her crutch slipped on the snow and went crashing through a tarpaulin-covered hole in the thatch, carrying its owner with it, into a loft half-filled with hay. There was no way of escape until somebody came by to rescue her. Freda therefore could do nothing but look down into the hazy light of the barn below; and presently, nursed into a comfortable warmth by the hay, she fell asleep.
She was awakened by being shaken pretty roughly, while a voice cried close to her ear:
“Now, then, I’ve got you; and if I let you get home with a whole bone in your little thievish body, you may think yourself jolly lucky, I can tell you.”
Having recognised the voice as Dick’s, Freda was not alarmed by the assumed ferocity of his tone. Besides, he had evidently mistaken her for somebody else. So she shook herself free from the hay, and sat up and looked at him. By that time he had got used to the gloom of the loft, and to her surprise, he drew back so quickly that he risked falling off the ladder. A little more contemplation, and then he murmured:
“Of course—it’s the hair!”
The net in which, in primitive fashion, she was accustomed to tuck away her hair, had been lost in her tumble through the roof, and her red-brown locks, which had a pretty, natural wave, had fallen about her ears and given to her pale face quite a new character. Dick, however, was not a young fellow looking idly at a pretty girl, but a man full of responsibilities and anxieties.
“You said last night,” he began abruptly, “that you had heard something at the ‘Barley Mow’ about us and your father. What was it?”
She answered in a low, modest voice, but without any fear
“You say my father is quarrelling with you. You wish to find out all his movements. Then if I tell you about them, I am betraying my own father!”
“I warn you that your principles won’t agree with his any more than they do with mine. Do as you would be done by is what you were taught at the convent, I suppose. Do as you are done by is the motto we live by here.”
“It seems very dreadful,” whispered Freda, “to do things that are wrong and not to mind!”
And the young man perceived that she had tears in her eyes.
“Don’t cry,” said he gently. “I shouldn’t have said what I have to you but that I wanted you to go back to your convent before you hear anything more to pain you. I want to take you to Presterby this afternoon, without your seeing my cousin Bob.”
“Ah!” cried Freda with a start. “Your cousin! Tell me, is he good to you? Are you fond of him?”
“Not particularly. That answer will do to both questions.”
“Then why do you stay here? Would it not be better for you to go away? They say—do they not say, that he makes you work for his advantage?”
He paused a few moments, and his face grew graver. Then he said abruptly: “Supposing I were to tell you that I am content to be taken advantage of, and that I’d rather live on here anyhow than like a prince anywhere else. I tell you,” he went on, with the ring of passion in his voice, “I love every foot of ground about here as you love your convent and your nuns; the stones of this old place are my religion. And so I shall live on here in some sort of hole-and-corner fashion, bringing grist to a mill that gives me neither honour nor profit, until——”
He stopped short. Freda was deeply moved; but she only asked him, in a constrained voice, if he would let her come down the ladder He ran rapidly down, held the ladder firm for her, and gently assisted her as she came near the ground, taking her crutch and returning it to her when her feet touched the floor.
“Poor little lame girl!” said he softly, and the words brought sobs into her throat. “Why, you’re crying! I didn’t hurt you, did I?”
“No-o, no,” said Freda, drawing herself away. “Let me go, please.”
“Well, say that we’re friends first.”
Freda raised her eyes, but her glance passed Dick and remained fixed on a face that appeared at the window beyond. A young man, with sandy hair and moustache, was looking in with a cynical grin. Dick turned quickly, when he saw the change on the girl’s face. His own expression altered also.
“Bob! Back already!” he cried.
The young man had climbed in. Nodding at his cousin, with a glance at Freda which she found exceedingly offensive, he asked:
“Well, and who is the little girl?”
Perhaps the girl’s mind, having retained a child-like purity, was able at once to detect the taint in that of Robert Heritage; but certainly the persistent stare of his small grey eyes, which he honestly believed to be irresistible, affected her no more than the gleam of a couple of marbles; while every other feature of his face, from the obtrusively pointed nose to the thin-lipped mouth, seemed to her to betray ugly qualities, the names of which she scarcely knew. He, on his side, regarded her face with a bold, critical stare, which changed into contempt the moment he caught sight of her crutch. Dick grew red with anger.
“You didn’t get my telegram then?” he said shortly, interposing his person to shield the girl from his cousin’s impudent gaze.
“No, I got no telegram. What was it about?”
“Come into the house and I’ll tell you.”
He moved to the door. Robert would not let him open it.
“What! and interrupt your studies of the maim, the halt, and the blind?” he asked, in a low voice which, however, the girl’s quick ears caught.
Freda had been reprimanded at the convent for occasional outbursts of passion. But she had never yet felt the force of such a torrent of indignation as seemed to sweep through her frame at this, the first sneer at her infirmity she had ever heard. She scarcely noticed Dick’s angry remonstrance; but raising her flushed face to Robert, she said:
“You can sneer at me now. Perhaps you will not when I am in the house of my father, Captain Mulgrave.”
“Come, that’s rather strong, little girl,” he said coolly “To be Mulgrave’s daughter—which you may be for anything I know—is one thing, but to live in his house is another. I can assure you he has made no preparations for your reception.”
His insolent tone stung Freda to a greater heat of passion.
“Perhaps you are not in my father’s confidence,” she said in a voice which shook a little. “If you had been, you might have known that he was going to visit Josiah Kemm.”
Without waiting to see the effect of her words, Freda ran out of the barn, across the court-yard, and up to the room she had slept in. There she put on her hat and cloak, and after waiting some time in fear lest she might be hunted out, stole out of the room and came, to her disgust, face to face with Blewitt. He had on a thick coat and riding-boots.
“I beg pardon, ma’am, but I was a-coming to inform you that I have been hordered by Mr. ’Eritage to go to the Abbey with a letter for your respected father, Captain Mulgrave. Now, ma’am, I should esteem it a honour to be sent to a gentleman like Captain Mulgrave on any hordinary errand. But knowing, as I happen to do, the himport of the letter, I feel it very different, I assure you, ma’am.”
Freda was too unsophisticated to guess by what simple means Blewitt had arrived at the knowledge he alluded to. But she was afraid he wanted to tell her something she ought not to hear, and she interrupted him hurriedly.
“Yes, I’m sure that all you say is quite—quite right,” she said nervously. “But I—I am going out, and I cannot——”
“You cannot stay under the roof of such people as them. Which I was sure, ma’am, that such would be your feelings. Barnabas Ugthorpe, the farmer, has been here with his cart a-inquiring after you; and I know where he is to be found now, if so be as you would like me to show you how to get out by a private door.”
“Oh, yes, please show me out,” cried Freda piteously, delighted at the thought of seeing her rough friend, whom she hoped to persuade to take her on to the Abbey.
“I will do so, ma’am,” answered Blewitt, who by this promise forced her to listen to him. “And if you could say a good word to the Captain for me that would induce him for to take a hard-working man into his
service, why, I could tell him a many little tales about the goings on in this house which would astonish him, and just show him how he misplaced his confidence in some people I could name.”
“How can you think my father could listen to such things!” Freda broke out indignantly.
“Well, ma’am, gentlemen’s ways is not always straight ways, when they wants pertic’ler to know things,” said Blewitt, drily though respectfully. “But the Captain’s a ’asty and ’aughty sort of gentleman as you don’t always quite know where to have him! and when he gets this letter, which threatens to do for him if he don’t give up all dealings with Josiah Kemm immediate, why he’ll be in such a taking that he’ll be more likely to do for me than to listen to anything what I can say.”
“Why do you take the letter then?”
The fact was that Mr. Blewitt did not wish to be off with the old love until he was quite sure of being on with the new. He put this to Freda, however, in a nobler light.
“You see, ma’am,” said he, “so long as I take Mr. ’Eritage’s wages, I must carry out his horders.”
“Yes, of course, of course,” said Freda, with almost a shriek of delight as Blewitt opened a little side-door and she found herself out of the house, standing in the snow under the grey old outer wall.
She found Barnabas just driving off from one of a group of cottages at the bottom of the lane. At her cry he stopped, waiting for her to come up.
“Barnabas!” she cried, quivering with anxiety, “won’t you drive me over to the Abbey? Oh, do, do! You will, won’t you?”
The farmer scratched his ear.
“Happen one o’ t’ young gentlemen ’ll droive ye over.”
“Oh no,” said Freda quickly. “I wouldn’t go back there for anything in the world!”
The farmer grinned, nodded, helped Freda into his cart, and started off at a much better pace than they had made with Josiah Kemm’s old mare the night before.
“Weel, lassie,” he said, as they jogged along, “ye’ve made a better conquest nor any scapegrace of a Heritage. That theer swell that was so kind to ye at t’ ‘Barley Mow,’ he’s gone clear creazed about
ye. When Ah left ye at t’ farm last neght, Ah fahnd him on t’ road, mahnding for to get to Presterby. Ah towd him he couldn’t the neght, an’ Ah tuck him back; an’ t’ missus, when she’d satisfied herself he warn’t a woman in disguise, was moighty civil. An’ he said sooch things abaht yer having a sweet little feace, an’ he said he should call at t’ Abbey to see ye.”
“Barnabas,” said Freda suddenly, “why did you look so mysterious last night when I told you that he had something to do with the government?”
The farmer gave her an alarmed glance, as he had done the night before, and said in a cautious tone:
“Ye’ve gotten a pair of sharp ears, an’ they hear more’n there’s ony need. Ye didn’t reeghtly unnerstand, lass.”
After this there came a long pause, during which Freda puzzled herself as to what the inhabitants of this district had been doing, to have such a fear of the government. It was getting dark when Barnabas broke the long silence by saying, as he pointed with his whip to the summit of a hill they were about to ascend:
“T’ Abbey’s oop top o’ theer.”
Freda was too much agitated to answer except by a long-drawn breath. The Abbey! Her father’s home! A terrible presentiment, natural enough after the scant experience she had had of his care, told her that there was no welcome waiting. She crouched down in the cart and clung to the farmer’s arm.
“Barnabas,” she whispered, “I’m afraid to go on. Drive slowly; oh, do drive slowly!”
But the robust farmer only laughed and jogged on at the same pace. The road, however, grew in a few minutes so steep that they could only proceed very slowly, and Barnabas got down to lead the horse and lighten his burden as he ploughed his way up. Traffic between the little town of Presterby and its neighbours had been so much hindered by the blockade of snow, that there were no wheelmarks on the white mass before them.
“Soomun’s been riding oop a horseback, though,” said Barnabas, as he looked at the print of hoofs.
“Perhaps the man Blewitt from the farm,” suggested Freda. “He said he was going to ride to the Abbey.”
“Oh, ay,” said the farmer with interest. “If he was cooming, noa doubt it’s him. Hey,” he went on, in a different tone, “Ah think Ah hear his voice oop top theer! He’s fell aht wi’ soomun by t’ sounds, Ah fancy.”
He stopped the cart a moment to listen. Plainly both Freda and he could hear the voices of men in angry discussion, the one coarse and loud, the other lower and less distinguishable.
“My father!” cried Freda, trembling.
“A’ reeght, lass, a’ reeght; doan’t ye be afraid. We’ll be oop wi ’em in a breace o’ sheakes.”
“Barnabas! Make haste, make haste! They’re quarrelling, fighting perhaps!” cried the girl in passionate excitement.
“Weel, Ah’ll go and see,” answered the farmer who, knowing more than his little companion did of the reckless and violent character of the disputants, was in truth as much excited as she was.
“He’s carrying a letter which he said would enrage my father!” cried Freda in a tremulous voice to Barnabas, who was already some paces ahead, running up the hill as fast as he could.
The road lay between stone walls of fair height, and was full of curves and windings; so that it would have been impossible, even in broad daylight, for the farmer to see the two men until he was close upon them. He was not yet out of Freda’s sight when a sharp report, followed by a second, and then by a hoarse cry, broke upon their ears. There was silence for a moment, and then the sound of galloping hoofs upon the snow. A riderless horse, bearing a man’s saddle, came down the hill, with nostrils dilated and frightened eyes. Barnabas, who considered a horse as rather more a fellow-creature than a man, set to work to stop the animal before making his way to the human beings. This accomplished, he tied the horse to the gate of a field a few yards higher up, and quickening his pace again, reached the top of the hill.
Here, in the middle of the road, were two figures, the one prone on the ground, the other kneeling in the snow beside him.
The kneeling man started and rose to his feet as Barnabas came up. He held in his left hand an open letter, and in his right a revolver, which, without resistance, he allowed the farmer to take.
“Captain Mulgrave!”
The Captain only nodded. Barnabas went down in the snow beside the second figure. He was on his face, but Barnabas knew, even before he attempted to raise him, that it was Blewitt, the servant from Oldcastle Farm. He was dead.
CHAPTER V.
T unfortunate Blewitt had never, in his lifetime, excited the liking or respect of any one. Selfish and mean, he had been tolerated because he was useful to his employers, who mistrusted him, and feared and avoided by the rest of his neighbours. But these facts, so it seemed to Barnabas Ugthorpe, heightened the tragedy of the manservant’s death. The honest farmer could not have expressed his thought in words, he but felt that the poor wretch whose body lay at his feet had somehow lost his chance forever.
As Barnabas stood there, considering the sight before him, Captain Mulgrave, who had not uttered a word, turned quickly, and was about to climb over the stone wall to the right, on his way back to the Abbey, when he felt a strong hand on his shoulder.
“Not quite so fast, Capt’n,” said Barnabas drily, “Ah want yer opinion o’ this metter.”
“My opinion is,” said Captain Mulgrave, shortly, “that this is the most d—d mysterious thing I ever saw And I’ve seen a few queer things in my life too.”
“Aye,” said Barnabas, “it’s a bad job this.”
He continued to stare at the dead man, and never once raised his eyes to the face of his living companion.
“Well,” said the Captain, after a long silence, “you don’t ask me to tell you how I found him?”
“Noa, sir, Ah doan’t,” said Barnabas drily.
“Well, why not?”
“Weel,” said the farmer, scratching his ear, “Ah doan’t knaw as Ah should knaw so mooch more’n Ah did afore.”
“You wouldn’t take my word then?”
“Ah doan’t know as, oonder t’ circumstances, Ah’d tek t’ word o’ any gentleman.”
“You think I had a hand in this man’s death?”
Barnabas paused a long time, still looking at the body, still scratching his ear.
“Aye, sir, it dew look like it,” he admitted at last.
“Well, at first sight it, dew,” mimicked Captain Mulgrave in a lighter tone than the farmer thought becoming. “But I tell you it’s all d—d nonsense, I was coming down here to see what state the roads were in, and I heard men’s voices, and then two shots. I was half-way across that field. I ran, got over the wall, and found the fellow lying like this, with the revolver in his hand. I took it up, and found that two chambers had been discharged. I looked up and down the lane, but I couldn’t see any one.”
“Noa,” said Barnabas with a movement of the head, “Ah should suppose not.”
He bent down over the body again, examining it.
“He’s shot in t’ back. Did it hissen, most loike.”
“Now what reason have you for supposing I shot him?”
“Weel, sir, asking yer pardon, but to begin with, ye’ve gotten t’ name o’ being free wi’ them things.” And he raised the revolver, which he still held in his hand. “Then, sir, Ah happen to knaw as he came to bring ye a letter as were not loike to put ye into a good humour.”
He glanced at the letter which Captain Mulgrave held.
“I don’t know how you came to hear about this letter, but you’re quite right as far as that is concerned. Only the man did not give it me; I found it on his dead body.”
“Ye found it moighty quick then, Capt’n. That’s not t’ weay moast on us cooms nigh a dead mon, to begin rummaging in ’s pockets before he’s cawld.”
“As to that, I guessed he’d come on an errand to me and had some message about him. And why should I have more respect for the fellow dead than I had for him alive? His carcase has no more value in my eyes than that of a carrion crow.”
“It’ll have a deal more, though, in t’ eyes of a jury, Capt’n.”
“Do you mean to try to hang me then, honest Barnabas?”
“Ah mean to tell what Ah seen, an’ leave it to joodge an’ jury to seay what they thinks on it.”
“And knowing me for such a desperate character you dare to tell me this to my face?”
“Happen Ah shouldn’t be so bold, but Ah gotten t’ revolver mysen.”
And Barnabas glanced at the weapon in his hand.
Captain Mulgrave laughed a little, and both men stood silent considering.
“I can’t think who can have had such a grudge against the poor devil as to shoot him,” he said at last, as if to himself. “It must have been some one on foot, for there are no hoof-marks about but those of the horse he was riding.”
Barnabas said nothing. With one steady look at Captain Mulgrave as if to tell him that he hadn’t done with him yet, the farmer examined the footprints in the snow round about. There were marks neither of wheels nor of hoofs further than this point, but there were footprints both of men and children, for this was the high road between Presterby and Eastborough, the next important town southwards along the coast.
“Aye,” said the farmer, when he had finished his inspection, “it mun ha’ been some one afoot, Capt’n, as you say.”
Captain Mulgrave had been considering the aspect of the affair, and he looked more serious when Barnabas uttered these words.
“Barnabas,” he said at last, “I begin to see that these devils, with their confirmed prejudice against me, may make this a serious business.”
“Aye, so Ah’m thinking too.”
“Give a dog a bad name, you know. Because I shot down four rascals in self-defence, I’m considered capable of depopulating the county in cold blood.”
“Aye, that be so. Leastweays we knaw ye doan’t hawd human loife seacred.”
“Well, and that’s true enough,—I don’t. There are men whom I should consider it justifiable to exterminate like vermin.”
“Weel, sir, we moast on us thinks that in our seacret hearts, only we moightn’t knaw wheer to stop if we let ourselves begin. But when we foind a mon wi’ t’ courage o’ these opinions, we have to put a stop to his little games pretty quick. It’s not that Ah bear ye any illwill, Capt’n, quoite t’ contrary: ye have t’ sympathy of all t’ coontrysoide, as ye knaw. But we must draw t’ loine soomwheer, an’ Ah draw it at murder.”
“You won’t take my word?”
“Can’t, Capt’n.”
“Will you take my money?”
“Noa, sir.”
“What are you going to do then? Go down into the town and set the police after me?”
Barnabas looked for a few moments puzzled and distressed. He would have given this high-handed gentleman into custody without a moment’s hesitation if it had not been for his little daughter, now on her way to her unknown home all unconscious of the tragedy which darkened it. On the other hand, he shrank from giving her into the care of a man whose hands were reeking with the guilt of a most cowardly murder. After pondering the matter, an idea struck him, and he raised his head with a clear countenance.
“Ah’ll haud my toongue aboot this business, if so be ye’re ready to mak’ a bargain.”
“Name your price then.”
“My price is that ye’ll give us yer room in these parts instead of yer coompany. Ye’ve gotten a yacht, Capt’n, an’ a rich mon’s weays o’ gettin’ aboot an’ makhin’ yerself comfortable. So Ah’m not droiving a hard bargain. But ye mun be aht of t’ Abbey by to-morrow, an’ all ye gotten to do is to mak’ soom provision for your little darter.”
Captain Mulgrave was more startled by the three last words than by all the rest of the farmer’s speech.
“My little daughter!” he repeated in a scoffing tone. “Yes, I’d forgotten her. But what do you know about her, eh?”
“Ah was bringing her oop t’ Abbey,” answered Barnabas, jerking his head and his thumb in the direction of the cart, which, however, was not in sight.
Captain Mulgrave frowned.
“D——d nuisance!” he muttered to himself.
“Eh, but Ah think Ah’ll tak’ her aweay again till ye’re gone, Capt’n,” said Barnabas drily. “T’ owd stoans will give her a better welcome home than ye seem loike to.”
“No, you may as well take her up now. I shall not see her. You don’t want to keep the girl out all day in the cold. I’ll just get across to the house now and tell Mrs. Bean to make a fire for her. By the time the cart comes round to the front I—I——” He hesitated, and
Barnabas saw that, under his devil-may-care manner, Captain Mulgrave was agitated. “By that time,” continued he, recovering himself, “it will be all ready for her, and—she’ll see nothing of me—I shall go away—to-night—I shall be glad to. I’m sick of this pestilential country, where one can only breathe by virtue of a special act of parliament. Sha’n’t see you again, Barnabas.” He moved away, and just as he put his hand on the stone wall to vault over, he turned his head to say, “Thanks for your kindness to the little one.”
Then he disappeared from the farmer’s sight hastily, as he heard the cart groaning and squeaking up the hill.
Freda had got tired of waiting for Barnabas, and after much vigorous shaking of the reins, which he had put into her hands, she had succeeded in starting the horse again.
“Barnabas!” she cried, as soon as she caught sight, in the gloom, of the farmer’s figure, “is that you?”
“Aye, lassie,” said he, placing himself between the cart and the dead body on the ground.
“Didn’t I hear you talking?”
“Aye, happen ye did.”
“Who were you talking to?”
“Eh, lass?” said he, pretending not to hear her, so that he might gain time for reflection.
“Who—were—you—talking to?” she asked slowly but querulously, for she was cold and tired, and full of misgivings.
“Eh, but Ah was talking to a mon as were passing.”
“Passing? He didn’t pass me.”
“Noa, lass, Ah didn’t seay as he did. Ye’re mighty sharp.”
“It’s because I don’t understand you. There’s something different about your manners. Something’s happened, I believe!”
“Eh, lassie, why, what’s coom over ye?”
“What’s that on the ground?”
She almost shrieked this, guessing something.
“Ye’ve gotten too sharp eyes, lassie. Ye’d better not ask questions.”
“Barnabas, Oh!—Barnabas, it’s not—not—my father!” whispered the poor child, clinging, over the side of the cart, to the rough hands the farmer held out to her.
“Noa, lass, noa.”
“Who is it? Tell me, quick.”
“Why, lass, it’s a poor mon as—as has been hurt.”
“He’s dead. He wouldn’t be there, so still, like that, if he was not— dead,” she whispered. “Who is it? Tell me, Barnabas.”
“Weel, Ah have a noetion—that he’s soommet loike servant Blewitt, oop to Owdcastle Farm.”
“Oh, Barnabas, it’s dreadful! Is he really dead?”
But she wanted no answer. She put her hands before her face, reproaching herself for having disliked the man, almost feeling that she had had a share in his tragic death.
“Who did it?” she asked at last, very suddenly.
Now Barnabas meant most strongly that the girl should not have the least suspicion that her father had a hand in this affair. The farmer’s soft heart had been touched as soon as Captain Mulgrave betrayed, by a momentary breaking of the voice, that he was not so utterly indifferent to his daughter as he wished to appear. Upon that reassuring sign of human feeling, Barnabas instantly resolved to hold his tongue for ever as to what he had seen. But unluckily, his powers of imagination and dissimulation were not great. Feminine wits saw through him, as they had done many a time before. While he was slowly preparing an elaborate answer, Freda had jumped at once to the very conclusion he wished her to avoid.
“Who did it?” she repeated in tones so suddenly tremulous and passionate that they betrayed her thought even to the somewhat slow-witted Yorkshireman.
“Lord have mercy on t’ lass!” cried he below his breath. “But Ah believe she knows.”
“Do you mean to say,” she went on in a low, monotonous voice, “that you saw my father—kill him?”
Her voice dropped on the last words so that Barnabas could only guess them.
“Noa, lass, noa,” said he quickly, “Ah didn’t see him do it.”
“Then he didn’t do it!” cried she, with a sudden change to a high key, and in tones of triumphant conviction. “You can tell me all about it now, for I’m quite satisfied.”
