[Show abstract][Hide abstract] ABSTRACT: Pulmonary artery sarcoma (PAS) is a rare but aggressive malignancy that leads to heart failure and death without treatment. Here we reviewed the presentation and management of patients treated at a national centre for pulmonary endarterectomy (PEA) and its associated hospital in Cambridge, UK.
Details of PAS patients treated at Papworth and Addenbrooke’s Hospitals between 2000 and 2014 were reviewed.
Twenty patients were diagnosed with PAS (11 males, 9 females), with a median age of presentation of 57 years (range 27–77). Presenting symptoms include dyspnoea (20), chest pain/tightness (7), oedema (5), constitutional symptoms (5), cough (3) and haemoptysis (3). Twelve patients were in group III/IV of the NYHA functional classification of symptoms. Initial CT scans were suggestive of thromboembolism in seven patients. Histological findings were of intimal sarcoma (13) and high grade sarcoma NOS (6).
Median overall survival (OS) was 17 months. Fourteen patients underwent PEA to relieve vascular obstruction, while six had inoperable and/or metastatic disease. There were three peri-operative deaths. Although there was no difference in median OS between patients who had PEA and those who did not (20 vs 17 months, P = 0.2488), surgery provided significant symptomatic improvement and some with long-term survival. Five patients received post-surgical chemotherapy (anthracycline +/− ifosfamide), and after completion four also had radiotherapy. Patients who received post-operative chemo- and radio-therapy showed a trend towards better survival compared to those who had surgery alone (24 vs 8 months, P = 0.3417). For palliative chemotherapy, partial responses were observed with the VID regimen and pegylated liposomal doxorubicin. Stable disease was achieved in a patient with intimal sarcoma with rhabdomyosarcomatous differentiation on third-line cisplatin and topotecan. The longest surviving patient (102 months) has had PEA, adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later, which were treated with radiofrequency ablation.
PAS often presents with symptoms mimicking pulmonary hypertension, heart failure or thromboembolic disease. PEA provides good symptomatic relief and in some cases, offers a chance of long-term survival. Although outcome appears to be better when PEA is combined with post-operative chemo- and radio-therapy, further studies are warranted.
[Show abstract][Hide abstract] ABSTRACT: Background:
We retrospectively analyzed data from patients who had been treated with trabectedin at our institution between April 2009 and August 2011.
Patients & methods:
Data from 25 patients with recurrent soft tissue sarcoma (leiomyosarcoma: n = 8; liposarcoma: n = 5) were used to assess the efficacy and safety of trabectedin 1.5 mg/m(2) given every 3 weeks.
Most patients (n = 14) had been heavily pretreated with ≥ 2 previous chemotherapy lines. Eight (32%) patients achieved a partial response according to dimensional and tumor density changes, and seven (28%) patients had stable disease for ≥ 3 months (clinical benefit rate = 60%; n = 15). Median progression-free survival was 6.4 months and overall survival 19.3 months. Common adverse events were fatigue, nausea, anemia and transient transaminase increases.
Treatment with trabectedin is effective and well tolerated in heavily pretreated soft tissue sarcoma patients. Tapering dexamethasone courses and switching trabectedin administration to an every 4 weeks schedule effectively dealt with persistent fatigue without compromising effectiveness.
[Show abstract][Hide abstract] ABSTRACT: Desmoplastic small round cell tumour (DSRCT) is a rare but frequently fatal sarcoma, and many of its characteristics still require further clarification.
We retrospectively analysed 41 patients treated at or referred to two regional referral centres in the UK between 1991 and 2012. A review of the current literature was also performed.
The median age of presentation was 27 years (range 16 to 45 years), with a male-to-female ratio of 3:1. Ninety percent of patients had disease in the abdomen. The median size of the presenting tumour was 13 cm (range 3.5 to 23 cm), and 80% had metastatic disease at diagnosis, mainly in the liver (33%) and lungs (21%). Time-to-progression (TTP) was 3.9, 2.3 and 1.1 months after first-, second- and third-line chemotherapy, respectively. First-line treatment with VIDE chemotherapy appeared to confer the longest TTP (median 14.6 months). Ifosfamide and doxorubicin resulted in TTP of >3.8 months when used in any-line setting. Eleven patients received targeted agents as part of a clinical trial. After a median follow-up of 14 months, the overall median survival (MS) was 16 months. There was no difference in MS with regards to age, gender, or size of the presenting tumour. Patients with extra-abdominal disease survived longer compared to those with tumours in the abdomen (all still alive vs MS of 15 months; P = 0.0246). Patients with non-metastatic intra-abdominal disease who underwent surgery had an MS of 47 months (16 months for those who did not have surgery; P = 0.0235). Radiotherapy for locoregional control in patients with metastatic intra-abdominal DSRCT was associated with longer survival (MS of 47 vs 14 months; P = 0.0147).
DSRCT is a rare but often fatal disease that mainly affects younger male patients. Those with intra-abdominal DSRCT have a poorer prognosis, although surgical resection for localised disease and radiotherapy in the metastatic setting are associated with improved survival. A patient's age, gender and size of presenting tumour do not have prognostic significance.
[Show abstract][Hide abstract] ABSTRACT: Background: Historically, GISTs were often misdiagnosed as other tumours. However, with the increasing awareness of GISTs, one needs to be careful in confirming the diagnosis since other tumours can simulate GISTs on endoscopy/imaging/histology. We report our 8 year experience of GIST mimics from the CGSG database. Methods: 250 cases discussed in the specialist multidisciplinary meeting from 2004 – 2012 were reviewed. Tumours initially suspected to be GISTs but turned out to be other tumours were included in this analysis. Patient demographics, endoscopic, imaging and histological features were analysed in 41 GIST mimics. Central review by specialist histopathologist was undertaken with immunohistochemical and molecular analysis to differentiate these tumours from GISTs. Results: GIST mimics N= 41. Median age 56 years (range 11 – 82 years), male:female ratio 1:1. Median size 8 cm (range 1.9 – 30 cm). Site of origin of tumours: stomach 34%, oesophagus/junction 15%, mesentery 12%, small bowel 10%, colon 5%, retroperitoneum 5%, pancreas 5%, liver 2% and indeterminate site of origin 12%. Suspicion of GIST was raised from imaging (46%), endoscopy (41%) and histology (39%). The histological subtypes of GIST mimics are summarised in the Table. Conclusions: Many benign and malignant tumours do mimic GISTs on imaging/endoscopy or histology. The diagnosis of GISTs should be made by a specialist multidisciplinary team with experience in imaging and histopathology. Distinguishing GISTs from their mimics is of critical importance both for prognosis and management.
Histological subtype % of GIST mimics Histological subtype % of GIST mimics
Leiomyoma 17 Inflammatory myofibroblastic tumour 5
Leiomyosarcoma 17 Solitary fibrous tumour 5
Carcinomas 10 Metastatic melanoma 2
Inflammatory fibroid polyp 7 Other sarcomas 10
Neuroendocrine tumour 7 Other benign lesions 15
Intraabdominal desmoid 5
[Show abstract][Hide abstract] ABSTRACT: Objective To illustrate the wider potential scope of image-guided intensity-modulated radiotherapy (IG-IMRT), outside of the "standard" indications for IMRT. Methods Nine challenging clinical cases were selected. All were treated with radical intent, although it was accepted that in several of the cases the probability of cure was low. IMRT alone was not adequate owing to the close proximity of the target to organs at risk, the risk of geographical miss, or the need to tighten planning margins, making image-guided radiotherapy an essential integral part of the treatment. Discrepancies between the initial planning scan and the daily on-treatment megavoltage CT were recorded for each case. The three-dimensional displacement was compared with the margin used to create the planning target volume (PTV). Results All but one patient achieved local control. Three patients developed metastatic disease but benefited from good local palliation; two have since died. A further patient died of an unrelated condition. Four patients are alive and well. Toxicity was low in all cases. Without daily image guidance, the PTV margin would have been insufficient to ensure complete coverage in 49% of fractions. It was inadequate by >3 mm in 19% of fractions, and by >5 mm in 9%. Conclusion IG-IMRT ensures accurate dose delivery to treat the target and avoid critical structures, acting as daily quality assurance for the delivery of complex IMRT plans. These patients could not have been adequately treated without image guidance. Advances in knowledge IG-IMRT can offer improved outcomes in less common clinical situations, where conventional techniques would provide suboptimal treatment.
No preview · Article · Jan 2013 · The British journal of radiology
[Show abstract][Hide abstract] ABSTRACT: Objectives The aims of this study are to assess the extent of ovarian movement on consecutive MRI examinations in patients with gynaecological malignancies and to define potential safety volumes around the ovaries that may avoid ovarian ablation during pelvic irradiation. Methods Patients with cervical, vaginal and endometrial cancer who underwent MRI examinations of the pelvis before and during radiotherapy were included in the study. The position of the ovaries was retrospectively determined on two consecutive axial and sagittal T(2) weighted MRI examinations of the pelvis. Ovarian movement was determined in craniocaudal, anteroposterior and mediolateral directions. Safety volumes were calculated by computing elliptical volumes based on the derived 95% and 99% reference intervals. Results 30 patients with a gynaecological malignancy were included. Both ovaries could be identified on the MRI examinations in all cases. The safety volumes around the ovaries encompassing 95% and 99% of ovarian movement were 11 and 25 cm(3) (95%), and 24 and 54 cm(3) (99%), for the left and right ovary, respectively. Conclusion Adding a safety volume around the ovaries may reduce the high radiation dose to the ovaries. This could potentially avoid ovarian ablation, reducing significant fertility morbidity.
Preview · Article · May 2012 · The British journal of radiology
[Show abstract][Hide abstract] ABSTRACT: Variability in gross tumour volume (GTV) definition is a major source of systematic error in conformal radiotherapy. This prospective study assesses the role of multidisciplinary collaboration between oncologists and radiologists in defining lung cancer volumes. Twenty patients with non-small cell lung cancer due to receive three-dimensional conformal radiotherapy formed the study population. GTVs were defined by a radiologist (GTVrad) and an oncologist (GTVonc) using available clinical information and imaging. A collaborative meeting was then held to agree on a final, common GTV (GTVfin) to be used for treatment planning, and differences analysed. The collaboration changed the GTV in 19/20 patients with a total of 50 regions being edited. Changes made were categorized as (a) differentiation of tumour from atelectasis or ground glass shadowing, (b) separation of tumour from vasculature, and (c) defining mediastinal extent of tumour. Oncologists were more confident in the GTVfin than the GTVonc. The radiologist took longer to define the GTV than the oncologist. Real-time collaborative GTV definition by a radiologist and oncologist is practical and feasible. This approach allows specific areas of uncertainty to be categorized and focussed on, reducing systematic error in GTV definition. The physician's approach to risk and decision making for each patient may also play a role.
[Show abstract][Hide abstract] ABSTRACT: To determine the incidence of capsular contracture (CC) requiring revisional surgery in patients receiving postoperative radiotherapy (RT) or no RT following mastectomy and immediate breast reconstruction.
One hundred and seventy-eight immediate breast reconstructions performed at the Cambridge Breast Unit between 1.1.2001 and 31.12.2005 were identified. RT was delivered using a standard UK scheme of 40 Gray in 15 fractions over 3 weeks. The influence of hormones and chemotherapy as well as postoperative RT on time to development of severe CC after implant-based reconstruction was explored in univariate and multivariate analysis.
One hundred and ten patients had implant-based reconstructions with a median follow-up of 51 months. In the RT group (41 patients), there were 8 patients with severe CC requiring revisional surgery, a crude rate of 19.5%, with actuarial rates of 0%, 5%, 5%, 21%, 30% and 30% at 1, 2, 3, 4, 5 and 6 years follow-up. In the unirradiated group, there were no cases of severe CC. This difference is highly significant (p<0.001). Hormones and chemotherapy were not significantly associated with severe CC.
This series showed a significantly higher rate of severe CC with postoperative RT. This finding has important clinical implications, when counselling patients for immediate breast reconstruction.
Full-text · Article · Oct 2008 · Radiotherapy and Oncology
[Show abstract][Hide abstract] ABSTRACT: To assess the local control and cranial nerve toxicity in vestibular schwannoma patients treated with fractionated conformal radiotherapy delivered using a linear accelerator.
Ninety-five patients were referred for consultation to the Oncology Department in Addenbrookes Hospital between 1996 and 2005. The 42 cases who received fractionated conformal radiotherapy are the subject of this analysis. All patients had radiological or symptomatic progression. Conformal radiotherapy was prescribed at 50Gy in 30 fractions over 6 weeks, delivered using a linear accelerator. Patients were immobilised using either a beam direction shell or a Gill Thomas Cosman relocatable stereotactic head frame.
The median age was 63 years (range 28-81) with 57% men. The average tumour size was 21.5mm on magnetic resonance imaging. Before treatment, 20 (48%) patients were deemed to have useful hearing on the affected side. The median follow-up was 18.6 months (range 0.3-6.5 years) and the actuarial local control rate at 2.5 years was 96.9% (one patient progressed after treatment). In previously hearing patients, the actuarial rate of useful hearing preservation was 100%, and the rate of mild hearing loss was 20% at 1 year and 26.7% at 2.5 years of follow-up. There were five neurofibromatosis type 2 patients treated, two of whom had useful hearing before radiotherapy. In one patient this was affected, with a 20dB loss, although he still has useful hearing. In those with normal facial nerve function before radiotherapy (n=40), this was preserved in 96.8% at 2.5 years. Trigeminal nerve function was preserved in all patients (n=38) who had normal nerve function before radiotherapy.
Although follow-up was relatively short in this single institution series, fractionated linear accelerator radiotherapy gave excellent local control, useful hearing preservation and retained cranial nerve function in vestibular schwannoma.
No preview · Article · Sep 2007 · Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: To evaluate the role of chest CT in the initial staging of testicular seminomatous germ cell tumours. All patients referred to Addenbrooke's Hospital with testicular seminoma from 1 January 2000 to 31 December 2005 were included and case notes retrospectively reviewed. One hundred and eighty-two patients with testicular seminoma were identified, with a median age of 37 years (range 19-74). Most patients had stage I disease (86%). Twenty-four patients had abnormal abdominal CT findings. One hundred and fifty-eight had normal abdominal CT findings but, on initial staging, chest CT reported abnormalities in 13 patients, which, on further follow-up CT were deemed to be irrelevant to the diagnosis of seminoma. There was a further patient with a normal CT abdomen in whom chest CT detected obvious metastatic disease, which was seen on chest x-ray. Overall 18 cases required additional investigations and follow-up for abnormalities subsequently found to be benign. There was a false-positive rate of 10% for initial staging with chest CT. This is the largest reported series of staging CT chest in testicular seminoma. In all patients with normal abdominal CT, normal chest x-ray and abnormal chest CT, subsequent follow-up investigations demonstrated that the lung lesions were incidental findings.
Preview · Article · Apr 2007 · British Journal of Cancer