Royal Marsden Hospital Research Articles

Results of radical chemoradiotherapy for oesophageal and junctional cancers: The Royal Marsden Hospital experience

Results of radical chemoradiotherapy for oesophageal and junctional cancers: The Royal Marsden Hospital experience

The results of local excision with or without postoperative adjuvant chemoradiotherapy for early rectal cancer among patients choosing to avoid radical surgery.

The study aimed to establish the oncological outcome of patients who opted for close surveillance with or without adjuvant chemoradiotherapy rather than radical surgery after local excision (LE) of early rectal cancer. The Royal Marsden Hospital Rectal Cancer database was used to identify rectal cancer patients treated by primary LE from 2006 to 2015. All patientswere entered in an intensive surveillance programme. Twenty-eight of 34 analysed patients had a high or very high risk of residual disease predicted by adverse histopathological features for which the recommendation had been radical surgery. Eighteen (52%) of the 34 had received radiotherapy following LE. Three-year disease-free survival for the 34 patients was 85% (95% CI 78.8%-91.2%) and overall survival was 100%. Twenty-two of 24 patients with a low tumour which would have required total rectal excision have so far avoided radical surgery and remain disease free at a median follow-up of 3.2years. The findings suggest that with modern MRI and clinical surveillance radical surgery can be avoided in patients following initial LE of a histopathologically defined high risk early rectal cancer. These findings are comparable with those obtained after major radical resection and warrant further prospective investigation as a treatment arm in larger prospective trials.

144: Radiotherapy practice in patients with extensive stage small-cell lung cancer responding to platinum chemotherapy at The Royal Marsden Hospital

144: Radiotherapy practice in patients with extensive stage small-cell lung cancer responding to platinum chemotherapy at The Royal Marsden Hospital

Ulrich Erich Otto Schirrmacher

Ulrich Erich Otto Schirrmacher (“Sherry”) was born in Turgau, Germany, and came to England with his parents in 1947. He went to school in Farnborough and then trained in medicine...

A Distributed International Patient Data Registry for Hairy Cell Leukemia

BACKGROUND: The study of rare diseases is limited by the uncommon nature of the conditions as well as the widely dispersed patient populations. Current rare disease registries such as the National Organization of Rare Diseases utilize centralized platforms for data collection; however because of their broad nature, these do not always capture unique, disease specific elements. Hairy Cell Leukemia (HCL) is a rare leukemia globally with approximately 900 new cases diagnosed in the US each year. The HCL Foundation undertook creation of a Patient Data Registry that collects data from multiple HCL Centers of Excellence (COE) around the globe to better understand the complications, treatment outcomes, disease subtypes, comorbid conditions, epidemiology, and quality of life of patients with HCL.METHODS: Investigators at The Ohio State University Department of Biomedical Informatics and Division of Hematology in collaboration with the HCL Foundation developed a Patient Data Registry (PDR) for the longitudinal capture of high quality research data. This system differs from other registries in that it uses a federated( rather than centralized) architecture, wherein data is queried and integrated in an on-demand manner from local registry databases at each participating site. Further, the data collected for use in the registry combines both automated exports from existing electronic health records (EHRs) as well as additional data entered via a set of web-based forms. All manually entered data comes from source documents, and data provenance spanning electronic and manually entered data is maintained via multiple technical measures. Patients may be enrolled at HCL COE, or, if they do not have access to a COE they may enroll via a web-based portal (www.hairycellleukemia.org). At this time due to regulatory requirements the web-based portal is available to US patients only. All data are de-identified (see Figure 1: De-Identification Workflow) which reduces regulatory burden and increases opportunities for data access and re-use. End users have access to data via a project-specific query portal.RESULTS: The Patient Data Registry has been deployed at The Ohio State University, Royal Marsden Hospital, and MD Anderson Cancer Center, and is undergoing deployment at the University of Rochester. Up to 25 international HCL COE may participate. In addition, US patients are actively entering the registry via the web-based portal. To date, 227 patients have been consented to the registry with 119 of these being via the web-based entry point.CONCLUSION: We created an international and web-based patient data registry which will enable researchers to study outcomes in HCL in ways not previously possible given the rarity of the disease.This work was made possible by research funding from the Hairy Cell Leukemia Foundation. [Display omitted] DisclosuresAndritsos:Hairy Cell Leukemia Foundation: Research Funding. Anghelina:Hairy Cell Leukemia Foundation: Research Funding. Lele:Hairy Cell Leukemia Foundation: Research Funding. Burger:Pharmacyclics: Research Funding. Delgado:Gilead: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Jones:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lozanski:Beckman Coulter: Research Funding; Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding. Montserrat:Morphosys: Other: Expert Testimony; Vivia Biotech: Equity Ownership; Gilead: Consultancy, Other: Expert Testimony; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses. Parikh:Pharmacyclics: Honoraria, Research Funding. Park:Genentech/Roche: Research Funding; Amgen: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tam:janssen: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heckler:Hairy Cell Leukemia Foundation: Research Funding. Payne:Hairy Cell Leukemia Foundation: Research Funding.

The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer

AimsDespite recent advances in the primary and secondary prevention of cervical cancer, a significant number of women present with or develop metastatic disease. There is currently no consensus on the standard of care for second-line systemic treatment of recurrent/metastatic cervical cancer. The purpose of this study was to evaluate the second-line systemic therapy used and the associated outcomes in a single cancer centre. Materials and methodsA retrospective review of patients with cervical cancer who received one or more lines of treatment for recurrent or metastatic cervical cancer at the Royal Marsden Hospital between 2004 and 2014 was carried out. The primary objective was to establish the types of second-line systemic treatment used. Secondary end points included objective response rate, progression-free survival and overall survival after second-line therapy. ResultsIn total, 75 patients were included in the study; 53 patients (70.7%) received second-line therapy for recurrent/metastatic disease. The most common second-line therapy was weekly paclitaxel (28.3%). Carboplatin-based chemotherapy (24.5%), targeted agent monotherapy within clinical trials (22.6%), docetaxel-based chemotherapy (13.2%), topotecan (9.4%) and gemcitabine (1.9%) were also used. The objective response rate to second-line therapy was 13.2%, which included three partial responses to carboplatin and paclitaxel, two partial responses to docetaxel-based chemotherapy, one partial response to weekly paclitaxel and one partial response to cediranib. Twenty-two patients (41.5%) achieved stable disease at 4 months. The median progression-free survival for women treated with second-line therapy was 3.2 months (95% confidence interval 2.1–4.3) and median overall survival was 9.3 months (95% confidence interval 6.4–12.5). Thirty-nine per cent of patients received third-line therapy. ConclusionSeventy per cent of patients treated with first-line systemic therapy for recurrent/metastatic cervical cancer subsequently received second-line treatment but response rates were poor. There remains no standard of care for second-line systemic therapy for advanced cervical cancer. Patients should be considered for clinical trials whenever feasible, including novel targeted agents and immunotherapy.

Clinical observations, 7.4. Blood pressure

British Journal of Healthcare AssistantsVol. 10, No. 11 ClinicalClinical observations, 7.4. Blood pressureMenna Lloyd JonesMenna Lloyd JonesSearch for more papers by this authorMenna Lloyd JonesPublished Online:10 Nov 2016https://doi.org/10.12968/bjha.2016.10.11.544AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Dougherty LLister S, eds (2011) Royal Marsden Hospital Manual Of Clinical Procedures. Student edn. 8th edn. Wiley-Blackwell, Hoboken NJ Google ScholarNHS Choices (2014) What is blood pressure? www.nhs.uk/chq/Pages/what-is-blood-pressure.aspx (accessed 31 October 2016) Google ScholarNational Institute for Health and Care Excellence (NICE) (2007) Acutely ill adults in hospital: recognising and responding to deterioration. www.nice.org.uk/guidance/CG50/chapter/1-Guidance (accessed 31 October 2016) Google ScholarPeate I, Wild K (2012). Clinical observations 4/6: assessing blood pressure. British Journal of Healthcare Assistants 6(8): 382–7 Link, Google ScholarRoyal College of Nursing (RCN) (2015) First Steps for Health Care Assistants. Blood Pressure. http://rcnhca.org.uk/clinical-skills/observation/blood-pressure/ (accessed 31 October 2016) Google ScholarTortora A, Anagnostakos N P (1990). Principles of Anatomy and Physiology. 6th edn. Harper and Row, London Google Scholar FiguresReferencesRelatedDetails 2 November 2016Volume 10Issue 11ISSN (print): 1753-1586ISSN (online): 2052-4420 Metrics History Published online 10 November 2016 Published in print 2 November 2016 Information© MA Healthcare LimitedPDF download

Patterns of disease relapse in primary extremity soft tissue sarcoma

Background Extremity soft-tissue sarcomas comprise a range of distinct histological subtypes. This study aimed to characterize the patterns of disease relapse in patients undergoing resection of primary extremity soft-tissue sarcoma. Methods All patients who had resection of primary extremity soft-tissue sarcoma at the Royal Marsden Hospital between January 2004 and January 2014 were identified from an institutional database. Results In the period examined, 556 patients underwent resection. The most common histological subtypes were undifferentiated pleomorphic sarcoma (169 patients, 30·4 per cent), well differentiated liposarcoma (63, 11·3 per cent), myxoid liposarcoma (62, 11·2 per cent), myxofibrosarcoma (54, 9·7 per cent) and leiomyosarcoma (39, 7·0 per cent). Local recurrence-free survival (LRFS) did not differ significantly between histological subtypes (P = 0·222). Distant metastasis-free survival (DMFS) and disease-specific survival (DSS) were found to differ significantly between subtypes (P < 0·001 for both DMFS and DSS), with the worst outcomes in patients with undifferentiated pleomorphic sarcoma (5-year survival rate: 56·8 (95 per cent c.i. 52·5 to 61·1) per cent for DMFS; 60·1 (55·6 to 64·6) per cent for DSS). However, on multivariable analysis, histological subtype was not found to be independently prognostic for LRFS, DMFS or DSS. Metastatic disease developed in 149 patients, with the lungs being the most common site of first metastasis (120 patients, 80·5 per cent). The site of first metastasis differed between subtypes, with extrapulmonary metastases predominant in myxoid liposarcoma (11 of 13 patients; P < 0·001). Conclusion Although histological subtype was not found to be an independent prognostic factor for oncological outcomes, the site of first metastasis differed significantly between subtypes.

1092P - Patterns of steroid use in diarrhoea and/or colitis (D/C) from immune checkpoint inhibitors (ICPI)

D/C is reported in up to 30% of patients treated with ICPI. Treatment algorithms advocate corticosteroids (CS) for moderate to severe symptoms. Patterns of endoscopic change and duration of CS are not described. Rates of CS toxicity in this group of patients are unclear. Medical records of melanoma patients treated with ICPI at the Royal Marsden Hospital from 2010-2015 were reviewed. The grade, duration of CS and infliximab (INF) use was recorded for each D/C episode. Patients who had flexible sigmoidoscopy (FS) were labeled as having macroscopic + /-microscopic (macro), microscopic (micro) changes alone or no changes (normal). CS toxicities were noted. 414 ICPI treatment episodes were undertaken in 353 patients. The rate of all-grade D/C was 23% (96/414): 27% (77/282) with ipilimumab, 8% (8/101) with anti-PD-1 agents and 38% (8/21) with combination ipilimumab + nivolumab. Median age 61 years, 54% were male.Tabled 1Steroid use by Flexible Sigmoidoscopy FindingsNReceived CS (%)No CSMedian CS duration days (range)UNK re CS durationOn CS at 3mths (%)UNK re CS at 3mths (%)INF (%)Median days CS to INF (range)Macro2724 (89)369 (5-278)410 (42)4 (15)8 (33)15 (6-60)Micro87 (88)151 (12-162)02 (29)00naNormal FS98 (89)140 (7-156)01 (13)02 (25)11 (2-20)Unknown65 (8)167 (36-91)11 (20)01 (20)9 Open table in a new tab 57% (55/96) required CS. 52% (50/96) underwent FS: 88% (44/50) received CS. Median duration of CS was higher in macro patients compared to a normal FS (69 vs 40 days; p = 0.07) and in micro patients compared to a normal FS (51 vs 40 days; p = 0.32; Table 1). 11% (11/96) of D/C was treated with INF and median CS duration in this population was 91 days, versus 52 days for those who received CS alone. Median time from first steroid to INF was 15 days (range 2-60). 25% (14/55) were on steroids at 3 months. At least 15% (8/55) developed new or worse diabetes, 13% (7/55) had mood change and 16% (9/55) developed an antibiotic-requiring infection. We describe different phenotypes of D/C associated with ICPI therapy. Appearances at FS may predict for duration of CS use. All patients should be monitored for stigmata of CS use and considered for PJP prophylaxis. CS sparing strategies should be prospectively evaluated.

881P - Response to chemotherapy in relapsed low-grade serous ovarian carcinoma: Royal Marsden series of 46 patients

Low-grade serous carcinoma (LGSC) of the ovary/peritoneum is characterised by relative resistance to chemotherapy, however there are no reported prospective studies of chemotherapy specifically in this rare subtype. The purpose of this study was to evaluate the response to chemotherapy in patients with relapsed LGSC treated at a single cancer centre. A search of a database of patients with histologically confirmed LGSC treated at the Royal Marsden Hospital between 1990-2015 was performed. Patients treated with chemotherapy in the relapsed setting with radiologically evaluable disease were included in the study. Histological confirmation of LGSC was performed by a gynae-oncology pathologist. Response was determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and confirmed by a radiologist. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS) and progression-free survival (PFS). Forty-six patients with relapsed LGSC with evaluable disease, treated with 77 separate chemotherapy regimens were included in the study. The median age at diagnosis was 49 years (range 22-80 years). There were 8 partial responses with an ORR of 10.4%. The median duration of response was 11.2 months. Stable disease was achieved in 58 of 77 (75.3%) treatment regimens. The stable disease rate at 6 months was 43%. The ORR for the platinum-sensitive cohort was 11.3% and 8.3% for the platinum-resistant cohort. The median OS was 62 months and median PFS was 8.2 months. Relapsed LGSC is relatively resistant to chemotherapy in comparison to the most common subtype, high-grade serous carcinoma. In our series, the response rate to chemotherapy (10.4%) for recurrent LGSC is higher than previously published retrospective series (3.7%). Chemotherapy should be considered an option for recurrent LGSC. There is an urgent need for better therapies and identification of LGSC patients who are more likely to respond to chemotherapy. Patients should be enrolled into clinical trials of novel targeted agents.

Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study

ObjectivesDose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores. MethodsData of patients with solid tumours aged <18 years at enrolment in their first dose-finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses. ResultsOverall, 248 patients were evaluated: median age, 11.2 years (range 1.0–17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2–7.4). Lansky/Karnofsky ≤80%, no school/work attendance, elevated creatinine and RMH score ≥1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12–17 years), p = 0.002, but not in children (2–11 years). ConclusionsPerformance status of 90–100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials.

Paratesticular Sarcoma: Typical Presentation, Imaging Features, and Clinical Challenges

To describe the major imaging features, together with clinical data, of paratesticular sarcomas. A retrospective analysis was performed of available imaging and clinical data of 77 consecutive cases of paratesticular sarcoma referred to the soft tissue sarcoma center at the Royal Marsden hospital between January 2006 and January 2015. Of the total cases, 87% had been referred postoperatively, 43% of which had been imaged preoperatively and 24% of which required re-resection due to incomplete initial excision. On imaging, abnormal fat was present in 73% of paratesticular liposarcomas, with solid or enhancing components indicating high-grade tumors. Leiomyosarcomas and rhabdomyosarcomas were all purely solid masses. Paratesticular sarcomas are rare, and lack of awareness may compromise treatment and outcome. They may be mistaken for common clinical problems such as inguinal hernias and epididymal cysts. Surgery for these presumed diagnoses may result in inadequate clearance and an increased risk of recurrence. A low threshold for imaging atypical paratesticular masses is needed, as this may better inform management.

Editorial introductions

Editorial introductions

Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials.

In phase 1 trials, an important entry criterion is life expectancy predicted to be more than 90days, which is generally difficult to predict. The Royal Marsden Hospital (RMH) prognostic score that is determined by lactate dehydrogenase level, albumin level, and number of metastatic sites of disease was developed to help project patient outcomes. There have been no systematic analyses to evaluate the utility of the RMH prognostic score for esophagogastric cancer patients. All nonpediatric phase 1 oncology trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program that began between 2001 and 2013 were considered in this review. Of 4722 patients with solid tumors, 115 patients were eligible for our analysis; 54 (47%) with cancer of the esophagus, 14 (12%) with cancer of the esopagogastric junction, and 47 (41%) with stomach cancer. Eighty-six patients (75%) had a good RMH prognostic score (0 or 1) and 29 patients (25%) had a poor RMH prognostic score (2 or 3). Disease control rates were significantly different between patients with good and poor RMH prognostic scores (49% vs 17%; two-sided Fisher's exact test P=0.004). The median treatment duration and overall survival for good and poor RMH prognostic score patients were significantly different (median treatment duration 2.1months vs 1.2months respectively, P=0.016; median overall survival 10.9months vs 2.1months respectively, P<0.001). In the multivariate analysis, age (60years or older), Eastern Cooperative Oncology Group performance status (2 or greater), and the RMH prognostic score (2 or 3) were significant predictors of poor survival. The RMH prognostic score is a strong tool to predict the prognosis of esophagogastric cancer patients who might participate in a phase 1 trial.

Patterns of disease relapse in primary extremity soft-tissue sarcoma.

Extremity soft-tissue sarcomas comprise a range of distinct histological subtypes. This study aimed to characterize the patterns of disease relapse in patients undergoing resection of primary extremity soft-tissue sarcoma. All patients who had resection of primary extremity soft-tissue sarcoma at the Royal Marsden Hospital between January 2004 and January 2014 were identified from an institutional database. In the period examined, 556 patients underwent resection. The most common histological subtypes were undifferentiated pleomorphic sarcoma (169 patients, 30·4 per cent), well differentiated liposarcoma (63, 11·3 per cent), myxoid liposarcoma (62, 11·2 per cent), myxofibrosarcoma (54, 9·7percent) and leiomyosarcoma (39, 7·0 per cent). Local recurrence-free survival (LRFS) did not differ significantly between histological subtypes (P = 0·222). Distant metastasis-free survival (DMFS) and disease-specific survival (DSS) were found to differ significantly between subtypes (P < 0·001 for both DMFS and DSS), with the worst outcomes in patients with undifferentiated pleomorphic sarcoma (5-year survival rate: 56·8 (95 per cent c.i. 52·5 to 61·1) per cent for DMFS; 60·1 (55·6 to 64·6) per cent for DSS). However, on multivariable analysis, histological subtype was not found to be independently prognostic for LRFS, DMFS or DSS. Metastatic disease developed in 149 patients, with the lungs being the most common site of first metastasis (120 patients, 80·5 per cent). The site of first metastasis differed between subtypes, with extrapulmonary metastases predominant in myxoid liposarcoma (11 of 13 patients; P < 0·001). Although histological subtype was not found to be an independent prognostic factor for oncological outcomes, the site of first metastasis differed significantly between subtypes.

A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife

BackgroundThis pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.MethodsPatients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy.ResultsTwenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy.ConclusionREIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer.

Validation of prognostic scoring and assessment of clinical benefit for patients with bone sarcomas enrolled in phase I clinical trials.

BackgroundWe sought to validate the Royal Marsden Hospital (RMH) and MD Anderson Cancer Center (MDACC) prognostic scoring systems for the selection of bone sarcoma patients for phase I clinical trials and to identify additional risk factors related to survival.Patients and MethodsWe retrospectively reviewed the baseline characteristics and outcomes of 92 bone sarcoma patients who were referred to MDACC's Phase I Clinical Trials Program.ResultsNinety-two patients with Ewing sarcoma (N = 47), osteosarcoma (N = 22), chondrosarcoma (N = 16), and other tumors (N = 7) were evaluated; 78 were enrolled in at least 1 of 43 different phase I trials. The median overall survival (OS) was 8.8 months (95% confidence interval [CI] = 6.8–13.7 months). Independent factors that predicted shorter survival were male sex, >2 metastatic sites, >3 previous therapies, hemoglobin level <10.5 g/dL, platelet count >200 x103/L, creatinine level ≥1.3 mg/dL, and lactate dehydrogenase level >ULN. Patients with good RMH scores (0-1) had longer OS than patients with poor RMH scores (2-3) (HR = 5.8, 95% CI = 2.9–11.0; P < 0.0001), as did patients with low MDACC scores (0-1) as compared to patients with higher MDACC scores (2–4) (HR = 3.2, 95% CI = 1.9–5.6; P < 0.0001).ConclusionThe RMH prognostic score can be used to predict the OS of bone cancer patients referred for phase I trials. The MDACC score added no value to the RMH score and therefore does not have a role in assessment of patients with bone tumors. Patients with advanced bone sarcomas should be considered for phase I trials.

Rapid and objective CT scan prognostic scoring identifies metastatic patients with long-term clinical benefit on anti-PD-1/-L1 therapy

BackgroundDrugs targeting programmed death receptor-1 (PD-1) and its ligand PD-L1 have shown activity in multiple malignancies. Considering their novel mechanism of action, whether traditional prognostic scores also apply to patients treated with these drugs is unknown. We investigated whether a baseline 3-point (pt) computed tomography (CT) scan (PS3-CT) score and a 7-pt prognostic (PS7) score allowed identifying long-term survivors on anti-PD-1/-L1 therapy. Materials and methodsWe reviewed 251 consecutive patients enrolled in phase I trials evaluating anti-PD-1/-L1 agents between 26th December 2011 and 7th September 2015. PS3-CT was calculated using high tumour burden (TB1D-RECIST > 9 cm), low skeletal muscle index (SMI < 53 cm2 m−2) and non-pulmonary visceral metastases (NPVM) (1 pt each). PS7 was calculated by adding lower performance status, decreased serum albumin, increased serum lactate dehydrogenase and more than two distant metastases (1 pt each). Effect on overall survival (OS) of each parameter was tested using Kaplan–Meier and multivariable Cox analyses. ResultsPS3-CT was a significant independent predictor of OS (hazard ratio [HR] = 1.39 [95% confidence interval {CI} = 1.07–1.81], p = 0.01) when compared to the Royal Marsden Hospital, Barbot and American Joint Committee on Cancer scores. High TB (n = 78), low SMI (n = 55) and NPVM (n = 146) were associated with poorer survival (p < 0.01). High TB and low SMI were independent predictors of OS (respective HR of death: 2.00 [95% CI = 1.38–2.88], p < 0.01 and 1.75 [95% CI = 1.15–2.66], p < 0.01). PS7 was a significant predictor of OS (HR = 1.40 [95% CI = 1.25–1.56], p < 0.01). ConclusionObjective and rapid-risk scoring based on three CT scan parameters allows identifying patients with prolonged OS on anti-PD-1/-L1 therapy, independently from conventional clinical–biological prognostic scores.

Jean Decima Jacomb (1894–1988), matron of The London Clinic, 20 Devonshire Place, London W1 from 1938 to 1949

Miss Jean Jacomb born into a wealthy family, was at the age of 22 a student nurse at St Bartholomew's Hospital, London in 1917 where she nursed convalescent soldiers from World War I. Her midwifery training was in the slums around Whitechapel where a nurses uniform and medical bag provided a safe passage in the East End of London. For a while she worked in South Africa and India and returning to UK in 1923 she progressed to appointment as matron at the now re-named Royal Marsden Hospital in Chelsea. In 1938 she was appointed matron to The London Clinic during the years of World War II following which in 1949 she retired at the age of 55. She then travelled the world extensively by ship, always first class. She died in 1988.

Robert J. Shalek, Ph.D., J.D.

We are saddened to report the death of Dr. Robert J. Shalek, who passed away at the age of 93 on April 20, 2015. Robert J. Shalek, Ph.D. was born in Chicago, IL in 1922. He earned his undergraduate degree in physics from the University of Illinois in Champaign. After graduating, he served in the US Army for 3 years as a Signal Corp officer. He returned home to Texas where his parents had moved and entered the graduate program at the Rice Institute (now Rice University). He earned two masters degrees (physics and mathematics) and went on to earn a Ph.D. in biophysics in 1953. Dr. Shalek was the second Rice Physics Fellow in the Department of Physics at the MD Anderson Hospital [currently The University of Texas MD Anderson Cancer Center (MDACC)]. During this time, he worked with Leonard Grimmett on one of the world's first 60Co units. Upon receiving his Ph.D. he spent a postdoctoral year at the Royal Cancer Hospital (now called the Royal Marsden Hospital) in London, England under the guidance of W. V. Mayneord, the Head of the Physics Department and author of the “Mayneord F factor.” After this postdoctoral year he returned to the Department of Physics at MDACC. He published over 100 scientific papers before retiring in 1985 after working at MDACC for 35 years. Among his many contributions to Medical Physics, he was Chairman of the Department of Radiation Physics (1961–1984) at MDACC following Dr. Leonard Grimmett and Dr. Warren Sinclair, both very experienced medical physicists from England. He and Dr. Gilbert Fletcher, the chairman of the Department of Radiation Therapy at MDACC from 1948 to 1981, recognized the need for medical physics quality assurance for national multi-institutional clinical trials and as such, along with the AAPM, proposed a center of physics quality assurance for clinical trials. He ultimately was awarded the first National Cancer Institute grant to create the Radiological Physics Center (RPC) and was its first Director from 1968 until 1985. He was one of AAPM's founding charter members and served as the AAPM's seventh president in 1966. He became a fellow of the AAPM and was awarded ASTRO's Gold Medal in 1996. He was the second recipient of the AAPM's William D. Coolidge Award in 1972 and the sixth recipient of the Marvin M. D. Williams Professional Achievement Award in 1994. His career has encompassed both basic research and the application of physics to clinical problems. His basic research included studies of oxygen reactions following radiation interactions1 and the proportion of direct and indirect radiation action in living cells.2 His clinically related work included the dosimetry of external treatment beams, brachytherapy dosimetry, and quality assurance in radiotherapy physics.3 In the 1960s he wrote one of the seminal papers4 on ferrous sulfate (Fricke) dosimetry that made chemical dosimetry available in the clinic. Also in the 1960s, he and his trainee (and later, colleague) Marilyn Stovall published a series of articles describing the MD Anderson method for implant dosimetry using computerized techniques.5–9 These publications helped disseminate these methods and enabled many institutions to introduce what were for the time very advanced brachytherapy calculation techniques. From right to left, Dr. Shalek, Dr. Hanson, and Dr. Ibbott at a reception in 2001 for Geoff Ibbott, the new RPC Director. While working at MDACC, Dr. Shalek studied law at the University of Houston during the evenings and received his J.D. in 1983. He lectured regularly on legal questions in medical physics and regularly gave professional legal advice to physicists. He also participated in medical malpractice suits, usually as an expert witness. Bob was especially proud of his book, Medical Physicists and Malpractice10 (authored with David Gooden) that outlines the legal framework of liability risk in radiation therapy, the impact on clinical physicists, and practical approaches for avoiding and managing such lawsuits. Dr. Shalek is survived by his wife Elaine V. Shalek, 6 children, 9 grandchildren, and 4 great grandchildren. His accomplishments in medical physics will be long remembered. Equally well known is the way he conducted himself throughout his career, always as a man of high principle and character. He truly was a credit to our profession and is remembered fondly by so many whose lives he touched during his incredibly successful and meaningful career.