Royal Marsden Hospital Research Articles

The cost of ipilimumab toxicity: a single-centre analysis.

There are no published data on the costs associated with investigating and managing toxicity from ipilimumab treatment in patients with metastatic melanoma. Patients treated with ipilimumab at The Royal Marsden Hospital between 1 September 2010 and 1 April 2013 were identified. Data on demographics, investigations and survival outcomes were collected. Patients with grade 3 or higher immune-related adverse events were identified, and costs of investigating and managing toxicities in them were calculated on the basis of standard National Health Service tariffs. Out of the 110 patients, 29 experienced grade 3/4 immune-related adverse events. The total cost of investigating and managing these patients was £140,680, or a median cost of £2860 per patient. Patients experiencing grade 3/4 toxicities had 1-, 2- and 3-year survival rates of 79, 59 and 46%, compared with 24, 17 and 15% in the group that did not experience significant toxicity (P<0.0005). The most common treatment-related toxicity identified was colitis. Two patients died from complications associated with ipilimumab colitis. The cost of ipilimumab toxicity is marginal in comparison with the total treatment cost. Patients treated with ipilimumab who develop significant toxicity have a higher than expected 1-, 2- and 3-year survival.

Developing a novel prognostic model to predict overall survival (OS) and 90 day mortality rate (90DM) for metastatic colorectal cancer (mCRC) patients in phase I trials.

e14618 Background: Phase I trials are a critical component of drug development. It is vital to select patients who are most likely to benefit. Prognostic scores like Royal Marsden hospital (RMH), P...

Validation of the Royal Marsden Hospital (RMH) prognostic score in 100 patients with advanced sarcoma enrolled in early phase clinical trials at a major cancer center.

10558 Background: Standard therapy refractory, metastatic and advanced sarcoma patients (pts) have few therapeutic options, and may benefit from enrollment in early stage clinical trials. The Royal...

Pazopanib-induced alopecia, an underestimated toxicity?

Pazopanib and sunitinib are treatment options for metastatic renal cell cancer (mRCC), with similar efficacy, and minor differences in their toxicity profile. Our experience has suggested that pazopanib-induced alopecia may be a potentially significant but previously under-reported toxicity. For this reason, we performed a retrospective review of the clinical records of all patients with mRCC treated with pazopanib at the Royal Marsden Hospital from European licensing until June 2013, and all patients treated with sunitinib over the same period. We found that 36 patients with mRCC were treated with pazopanib and 85 patients with sunitinib. Four of the 36 (11%) patients treated with pazopanib developed alopecia severe enough to warrant a wig versus none of 85 patients treated with sunitinib (p = 0.007). In conclusion, grade 2 pazopanib-induced alopecia was reported at significantly higher rates when compared to sunitinib-induced alopecia. Hence, in our view, patients should be informed about this potential toxicity when discussing the treatment options for mRCC.

P153. Use of acellular dermal matrix (ADM) in nipple reconstruction following breast reconstruction; the ‘central-pillar technique’

P153. Use of acellular dermal matrix (ADM) in nipple reconstruction following breast reconstruction; the ‘central-pillar technique’

P152. Is lipomodelling after breast cancer safe?

P152. Is lipomodelling after breast cancer safe?

P138. Do patients diagnosed with phyllodes breast tumours need long term follow up?

P138. Do patients diagnosed with phyllodes breast tumours need long term follow up?

Abstract P3-11-05: Neoadjuvant chemotherapy in invasive lobular breast carcinoma: Comparison of response, surgery and disease free survival with invasive ductal carcinoma

Abstract Background Lobular breast cancer (ILC) has been reported to be associated with a lower rate of pathologic complete response (pCR) and breast conserving surgery following neoadjuvant chemotherapy compared with ductal carcinoma (IDC). ILC is predominantly oestrogen receptor positive, HER-2-ve and histologic grade 1 or 2. Oestrogen receptor positive breast cancer has been shown to have poorer responses to neoadjuvant chemotherapy. HER-2 positivity is associated with better responses to anthracycline based neoadjuvant chemotherapy than HER-2 negative, and substantially improved pathological complete response (pCR) rates relative to HER-2 negative disease with the use of HER-2 targeted agents in this patient group. This study investigates response and disease free survival of ILC compared with IDC. Methods Patients with ILC and IDC treated with neoadjuvant chemotherapy were identified from the prospectively collated breast unit database at the Royal Marsden Hospital. Demographic, tumour, treatment and outcome data was obtained from the database and hospital electronic patient record system. Statistical analysis was undertaken comparing IDC and ILC. Clinical response rates, pCR rates, breast conserving surgery rates, and disease free survival were analysed. Clinical response was defined as those with partial response (≥50% reduction in the product of breast tumour size from baseline measurement), or complete clinical response (no clinically palpable breast tumour). Subgroup analysis was performed on ER+ve, HER-2–ve and HER-2 unknown cases. Results A total of 1017 patients were identified. Of these, there were 920 IDC and 97 ILC cases. Median age at commencement of neoadjuvant chemotherapy was 47.9 years (range 23.6-74.9). Median follow-up was 7.6 years (range 0.2-26.5). Pathologic response rates were available for 717 patients. 119 (19%) IDC had pCR, and 1 (1.1%) ILC (p &amp;lt;0.001). Of the patients with clinical response data available, 762 (82.8%) of the IDC and 74 (76.3%) of the ILC had a clinical response (p 0.19). Of the 804 IDC patients who underwent surgery, 480 (59.7%) had breast conserving surgery, while of the 89 lobular patients 33 (37.1%) underwent breast conserving surgery (&amp;lt;0.0001). Median disease free survival was 10.9 years (95%CI 8.6-13.2) for IDC and 10.1 years (95%CI 7.3-12.9) for ILC (p 0.318). Within the ER+ve, HER2-ve/unknown group there were 403 IDC and 82 lobular patients. pCR results were available for 148 (30%) of the patients. 41 (15.8%) in the IDC and 1 (1.3%) in the ILC group had pCR (p=0.001). 335 (83.1%) in the IDC group and 64 (78.0%) in the ILC group had a clinical response (p 0.27). Breast conserving surgery rates were 212 (57.6%) in the ductal group and 30 (39.0%) in the lobular group (p 0.003). Conclusion Within the cohort entire rates of pCR and of breast conserving surgery were lower for those with ILC compared with IDC. Despite lower rates of pCR and breast conserving surgery in ILC, there was no difference in clinical response rates or in disease free survival compared with IDC. Significant differences in pCR and breast conserving surgery rates between ILC and IDC persisted on subgroup analysis of those with ER+ve HER2-ve/unknown breast cancer. Citation Format: Hilary L Martin, Geraldine Walsh, Komel Khabra, Tabitha Skinner, Ian E Smith. Neoadjuvant chemotherapy in invasive lobular breast carcinoma: Comparison of response, surgery and disease free survival with invasive ductal carcinoma [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-05.

Selective organ preservation with neo-adjuvant chemotherapy for the treatment of muscle invasive transitional cell carcinoma of the bladder.

Background:Radiotherapy for muscle invasive bladder cancer (MIBC) aims to offer organ preservation without oncological compromise. Neo-adjuvant chemotherapy provides survival advantage; response may guide patient selection for bladder preservation and identify those most likely to have favourable result with radiotherapy.Methods:Ninety-four successive patients with T2-T4aN0M0 bladder cancer treated between January 2000 and June 2011 were analysed at the Royal Marsden Hospital. Patients received platinum-based chemotherapy following transurethral resection of bladder tumour; repeat cystoscopy (±biopsy) was performed to guide subsequent management. Responders were treated with radiotherapy. Poor responders were recommended radical cystectomy. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method; univariate and multivariate analyses were performed using the Cox proportional hazard regression model.Results:Response assessment was performed in 89 patients. Seventy-eight (88%) demonstrated response; 53 (60%) achieved complete response (CR); 74 responders had radiotherapy; 4 opted for cystectomy. Eleven (12%) demonstrated poor response, 10 received cystectomy. Median survival for CR was 90 months (95% CI 64.7, 115.9) compared with 16 months (95% CI 5.4, 27.4; P<0.001) poor responders. On multivariate analysis, only response was associated with significantly improved PFS, OS and DSS. After a median follow-up of 39 months (range 4–127 months), 14 patients (16%) required salvage cystectomy (8 for non-muscle invasive disease, 5 for invasive recurrence, 1 for radiotherapy related toxicity). In all, 82% had an intact bladder at last follow-up after radiotherapy; 67% had an intact bladder at last follow-up or death. Our study is limited by its retrospective nature.Conclusions:Response to neo-adjuvant chemotherapy is a favourable prognostic indicator and can be used to select patients for radiotherapy allowing bladder preservation in >80% of the selected patients.

Fast-tracking novel drugs in pediatric oncology

Fast-tracking novel drugs in pediatric oncology

80P - Role of Treatment in International Differences in One-Year Mortality From Early Stage Non-Small Cell Lung Cancer: a Tentative Answer From the International Cancer Benchmarking Partnership Study

T. Solomon1, M.D. Peake2, J. Butler3, M.P. Coleman1, W.K. Evans4, E. Jakobsen5, M. Boyer6, T.B. Johannesen7, B. Rachet1 Cancer Research UK Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK Department of Respiratory Medicine, Glenfield Hospital, Leicester, UK Royal Marsden Hospital, London, UK Juravinski Cancer Centre at Hamilton Health Sciences, Cancer Care Ontario, Toronto, ON, Canada Odense University Hospital, Odense, Denmark Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, Australia Norwegian Cancer Registry, Oslo, Norway Aim: International differences in lung cancer survival are well known. Using population-based data, we assessed if variation in the provision of treatment may explain some of this variation, focusing on early-stage non-small cell lung cancer (NSCLC) where guidelines recommend resection of curative intent.

Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy

The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques. Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVs were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage. In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm(3), 326.7 cm(3), 310.3 cm(3), and 256.7 cm(3), respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm(3) (with 0 mm BEM), 17.4 cm(3) (1-mm BEM), 10.8 cm(3) (2-mm BEM), 6.9 cm(3) (3-mm BEM), 5.0 cm(3) (4-mm BEM), and 1.4 cm(3) (5-mm BEM) in comparison with an overlap of 9.2 cm(3) seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage. Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.

First line palliative chemotherapy in elderly patients with advanced soft tissue sarcoma.

BackgroundThe efficacy and toxicity of first line palliative chemotherapy for soft tissue sarcomas (STS) in the elderly is poorly described.MethodsPatients over the age of 65 years receiving first line chemotherapy for advanced non-GIST STS January 1998 - January 2012 at the Royal Marsden Hospital were identified. Data regarding survival and predictive factors were collected retrospectively.Results120 patients (52 females) with a median age of 72 (range 65–83) were treated. The most common histological subtypes were undifferentiated sarcoma (30%), leiomyosarcoma (27%), angiosarcoma (14%). 42% of patients had high grade tumours. 70% of patients had metastatic disease at presentation; lung metastasis being the most common disease site (72%). 80% received single agent chemotherapy, mostly with doxorubicin (60%). The median number of cycles was 2 (IQR 3). A partial response was reported in 20% of patients with disease stabilisation in a further 20%. 38% of patients were hospitalised for chemotherapy related toxicity. The median overall survival (OS) was 6.5 months (95% CI 4.7-8.3). Anaemia, lymphopenia, hypoalbuminemia, sarcoma subtype and co-morbidities were predictive for overall survival.ConclusionThe overall survival for elderly patients with STS is poor but several predictive factors have been identified. Hospital admissions for chemotherapy related toxicity are common.

Hormonal treatments in metastatic endometrial stromal sarcomas: the 10-year experience of the sarcoma unit of Royal Marsden Hospital.

BackgroundHormonal manipulation is sometimes recommended in the treatment of metastatic endometrial stromal sarcoma, but there are few data assessing the efficacy of endocrine therapies in this subtype of uterine sarcomas.MethodsWe performed a retrospective electronic medical record review of patients with metastatic ESS treated with a hormonal agent at Royal Marsden Hospital between 1999 and 2011. We assessed progression-free survival (PFS), objective response and toxicity profile among patients with measurable disease.ResultsThirteen patients with metastatic ESS were treated with hormonal therapies. Hormone receptor status (estrogen and progesterone receptors) was assessed in 9 out of 13 patients and in all of them it was moderately to strongly positive. Aromatase inhibitors (AIs) were prescribed as first endocrine line in 11/13 patients and progestins in the remainder, while in 2nd line treatment AIs were prescribed in 7/10 patients, followed by progestins and GnRH analogues. Median PFS for 1stline was 4.0 years (95% CI: 2.4 – 5.5 years) with 5-year progression-free rate of 30.8% (95% CI: 5.7 – 55.9%), both of which reflect the indolent natural history of ESS. Best objective response was partial response (PR) in 6/13 patients (46.2%; 95% CI: 19.2 – 74.9) and clinical benefit rate (defined as complete response + PR + stable disease ≥6 months) was 92.4% (95% CI: 64.0 – 99.8%; 12/13 patients). Median PFS for 2nd line was 3.0 years (95% CI: 2.0 – 4.1 years) with 2-year progression-free rate of 88.9% (95% CI: 68.3 – 100.0).ConclusionsIn this cohort of metastatic ESS patients, 1st line endocrine treatment achieved objective response in 46.2% of them and clinical benefit in 92.4%. Tamoxifen and hormone replacement therapy should not be prescribed in patients with ESS due to their detrimental effects. Until more solid data are available, a reasonable recommendation would be that 1st line treatment with an endocrine treatment, preferably with an AI. Moreover, in view of the positive outcomes of our patients that received 2nd/3rdline endocrine treatments, all available hormonal options should be used in sequence in the management of ESS.

Do elderly patients benefit from enrollment into Phase I Trials?

Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. While the Royal Marsden Hospital (RMH) prognostic score (albumin, lactate dehydrogenase [LDH], number of metastatic sites) is validated in this setting, its utility among the elderly is uncertain. A total of 296 consecutive patients who were treated in 20 phase I trials from 2005 to 2012 in our unit were analysed. Clinical characteristics and outcomes between young (<65, n=202) and older patients (≥65, n=94) were compared. The median age of the older patients was 69 years (65-84) and 71% were males. Although elderly patients had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 months versus 9.9 months, p=0.68) and clinical benefit rate (69% versus 56%, p=0.07) compared to younger patients after median follow-up of 7.1 months (0.36-50.6 months). Age (p=0.23) did not have any bearing on occurrence of grade 3/4 toxicities. Twenty-six percent of elderly patients experienced grade 3/4 toxicities. The prognostic factors for overall survival (OS) identified in multivariate analysis were prior lines of chemotherapy (0-2 versus ≥3), baseline sodium levels (≥135 versus <135 mmol/L) and platelet levels (≤400 versus >400×10(9)). We developed a risk nomogram based on the factors prognostic of survival with concordance index of 0.65. The RMH model yielded a concordance index of 0.635. Elderly patients enrolled into phase I clinical trials had similar survival outcomes and toxicity profiles compared to younger patients. Risk scoring models to aid patient selection need further clarification.

Series 4.7. Meeting fluid requirements

British Journal of Healthcare AssistantsVol. 9, No. 3 ClinicalSeries 4.7. Meeting fluid requirementsMenna Lloyd JonesMenna Lloyd JonesSearch for more papers by this authorMenna Lloyd JonesPublished Online:12 Mar 2015https://doi.org/10.12968/bjha.2015.9.3.119AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Age UK (2013) Thousands die from thirst in care homes. http://tinyurl.com/qb2sgy2 (accessed 19 February 2015) Google ScholarCampbell N (2012) Dehydration: best practice in the care home. Nursing and Residential Care 14(1): 21–5 Link, Google ScholarDougherty L, Lister S, eds (2012) Royal Marsden Hospital Manual Of Clinical Procedures. Student edn, 8th edn. Wiley-Blackwell, London Google ScholarFrancis R (2013) Mid Staffordshire NHS Foundation Trust Public Inquiry. www.midstaffpublicinquiry.com (accessed 19 February 2015) Google ScholarJohnston E (2007) The role of nutrition in tissue viability. http://tinyurl.com/klxfpfm (accessed 19 February 2015) Google ScholarNHS Choices (2013) Dehydration. http://tinyurl.com/d9hrg53 (accessed 24 February 2015) Google ScholarRoyal College of Nursing (RCN) (2007) Water for Health: Hydration Best Practice Toolkit for Hospitals and Healthcare. http://tinyurl.com/3a5rdag (accessed 24 February 2015) Google ScholarShepherd AB (2013) Water, water, everywhere and not a drop to drink. Nursing and Residential Care 15(8): 530–7 Link, Google Scholar FiguresReferencesRelatedDetails 2 March 2015Volume 9Issue 3ISSN (print): 1753-1586ISSN (online): 2052-4420 Metrics History Published online 12 March 2015 Published in print 2 March 2015 Information© MA Healthcare LimitedPDF download

Series 4.4. Measuring height and weight

British Journal of Healthcare AssistantsVol. 9, No. 3 ClinicalSeries 4.4. Measuring height and weightMenna Lloyd JonesMenna Lloyd JonesSearch for more papers by this authorMenna Lloyd JonesPublished Online:12 Mar 2015https://doi.org/10.12968/bjha.2015.9.3.122AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References British Association of Parenteral and Enteral Nutrition (BAPEN) (2014) 10 key characteristics of good nutritional care in hospitals. http://tinyurl.com/27wr3mn (accessed 19 February 2015) Google ScholarDepartment of Health (DH), Age UK (2014) The Hospital Food Standards Panel's Report On Standards Of Food And Drink In NHS Hospitals. http://tinyurl.com/keqqev7 (accessed 19 February 2015) Google ScholarDougherty L, Lister S, eds (2012) Royal Marsden Hospital Manual Of Clinical Procedures. Student edn, 8th edn. Wiley-Blackwell, London Google ScholarNational Institute for Health and Care Excellence (NICE) (2006) NICE Guidelines [CG32]: Nutrition Support In Adults: Oral Nutrition Support, Enteral Tube Feeding And Parenteral Nutrition. www.nice.org.uk/guidance/cg032 (accessed 19 February 2015) Google Scholar FiguresReferencesRelatedDetails 2 March 2015Volume 9Issue 3ISSN (print): 1753-1586ISSN (online): 2052-4420 Metrics History Published online 12 March 2015 Published in print 2 March 2015 Information© MA Healthcare LimitedPDF download

The neutrophil–lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials

Background:Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil–lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.Methods:This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.Results:The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0–1 in 66% and 2–3 in 34%. The median NLR was 3.08 (IQR 2.06–4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.Conclusions:NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.

Pazopanib as first line treatment for solitary fibrous tumours: the Royal Marsden Hospital experience

BackgroundSolitary Fibrous Tumour (SFT) is a rare soft tissue neoplasm, described in several locations in the body. It is classified as intermediate malignant potential with low risk of metastasis and has a low tendency to recur after primary surgery.MethodsWe performed a prospective data collection of the patients with SFT presented to the Royal Marsden Hospital from January to December 2013, and treated with pazopanib in first line. Demographics, anatomic primary sites, treatment and survival outcomes were collected from patients’ electronic records.Results13 patients (54% females) were identified with a median age of 51 years (range 37–77). Most of the patients (77%) were diagnosed with extra-thoracic SFT. All the patients received first line treatment with pazopanib for metastatic disease. Median overall survival (OS) was 13.3 months. Median progression free survival (PFS) was 4.7 months. No statistically significant difference was found in OS and PFS between primary thoracic SFT and primary extra-thoracic SFT. According to RECIST, one partial response (9%) and eight disease stabilizations (73%) were found as best responses. Using Choi criteria, there were 5 partial responses (46%) and 4 stabilizations (36%).ConclusionOur prospective data confirm that anti-angiogenic drugs are active in SFT. PFS and overall response do not appear significantly lower than other reported series on the same disease. Furthermore, pazopanib is a drug already licensed in soft tissue sarcomas and these data suggest its activity also in this particular subtype of sarcomas.

Peter Loy de Villiers Hart

Peter Hart trained at the Royal Marsden and Westend hospitals. He worked as a consultant physician—initially in Kuala Lumpur, Malacca, and Malawi—before joining the Brunei General Hospital in 1962. Starting...