• A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation.

      Sirohi, B; Powles, R; Chopra, Rajesh; Russell, Nigel; Byrne, J L; Prentice, H Grant; Potter, M; Koblinger, S; Leukaemia and Myeloma Unit, Royal Marsden Hospital, Sutton, Surrey, UK. (2006-07)
      This open-label, dose-escalation study assessed the maximum tolerated dose (MTD) of the new antifungal micafungin in patients undergoing haematopoietic stem cell transplantation (HSCT). Participants received 3, 4, 6 or 8 mg/kg/day micafungin intravenously from 7 days to a maximum of 28 days or until neutropaenia resolved. The MTD was defined as the highest dose not causing the same Grade 3 or 4 adverse event in three or more patients. All 36 participants received >/=8 days treatment for a median of 18 days (range: 8-28); 1 patient withdrew consent and a further 11 discontinued to receive another systemic antifungal agent for a suspected infection. No case of confirmed invasive fungal infection occurred. Adverse events were those expected for patients undergoing HSCT and showed no evidence of dose-related toxicity. Criteria for MTD were not met; no patient had a Grade 3 or 4 adverse event considered causally related to micafungin. Thus, the MTD of micafungin can be inferred to be 8 mg/kg/day or higher.
    • A study to explore the patient's experience of peritoneal surface malignancies: pseudomyxoma peritonei.

      Witham, Gary; Willard, Carole; Ryan-Woolley, Bernadette; O'Dwyer, Sarah T; Peritoneal Tumour Service, Christie Hospital NHS Foundation Trust, Withington, Manchester M20 4BX, UK. G.Witham@mmu.ac.uk (2008-04)
      Pseudomyxoma peritonei (PMP) is a rare tumour originating from the appendix and producing extensive mucus accumulation within the abdomen and pelvis. Since UK government policy reinforces the importance of involving patients in the delivery of healthcare, it is essential to explore patients views so that service development can be fully responsive to the patients need. The primary objective of this study was to explore the impact of PMP on the lives of patients. The secondary objectives were to explore the sources of psychological support for patients, the symptoms experienced and their information concerns. In-depth interviews were conducted with a purposive sample of 13 patients. The interviews were tape recorded, with permission, transcribed in full and analysed for content and emerging themes. The emergent themes included significant uncertainty about the diagnosis and treatment of this rare condition. The difficulties associated with confirming an initial diagnosis and living with an uncertain prognosis were highlighted. Patients' choice and access to support by a specialist team were important themes. The data highlighted the particular needs of this under-researched patient group and provided evidence to further develop patient support, particularly using the Internet.
    • A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity.

      Gibb, Adam; Greystoke, Alastair; Ranson, Malcolm R; Linton, Kim M; Neeson, Susan M; Hampson, G; Illidge, Timothy M; Smith, Ed; Dive, Caroline; Pettitt, A; et al. (2013-11-12)
      Background:Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1-3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured.Methods:Dose escalation of doxorubicin in cycles 1-3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m(-2)) with doxorubicin reduced to 25 mg m(-2) or omitted in cycles 4-6 to maintain cumulative exposure of 103-130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD.Results:Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m(-2), so 45 mg m(-2) was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD.Conclusion:Escalated ABVD incorporating doxorubicin at 45 mg m(-2) in cycles 1-3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies.
    • Study to investigate the correlation between the number of sentinel lymph nodes and the incidence of micro-metastases

      Yoon, W. Y.; Oudit, Deemesh; The University of Manchester, Manchester (2020)
      Introduction: Sentinel lymph node (SLN) biopsy is a technique that identies micro-metastases within lymph nodes in the regional nodal basin. It is useful in the accurate staging of tumours such as skin malignancies because of the reliable pattern of lymphatic drainage. This study aims to investigate whether there is a correlation between the number of SLNs and the incidence of micro-metastases. Method: A retrospective review of data from 742 patients with metastatic melanoma who underwent SLN biopsy at The Christie Hospital from 2008 to 2019 was performed. Result: A total of 742 patients with 743 primary melanomas of the limbs were identi?ed. Fifty-three of 328 cases had micro-metastases with 1 SLN (16.2%) compared to 59/296 (19.9%) with 2 SLNs, 22/83 (26.5%) with 3 SLNs, 8/24 (33.3%) with 4 SLNs and 4/7 (57.1%) with 5 SLNs. The remaining 5 cases had 6 or more SLNs, but the incidences of micro-metastases were negligible. Conclusion: Our findings indicate that there is a direct correlation between the number of sentinel nodes harvested at the time of surgery and the incidence of micro-metastases in patients with cutaneous melanoma independent of other prognostic factors. We have found that the incidence of micro-metastases increases as the number of SLNs increase.
    • A study to investigate the prognostic value of interval sentinel lymph nodes in melanoma

      Yoon, W. Y.; Oudit, Deemesh; The University of Manchester, Manchester (2020)
      Introduction: Many studies show that the lymphatic drainage pattern of patients is variable. Some patients have drainage to unconventional nodal basins. Interval nodes are lymph nodes which exist between primary melanomas and regional nodal basins and occur only in a small number of patients. It is known that interval nodes can be the only positive sentinel lymph node (SLN) in melanoma patients. This study aims to investigate the prognostic value of interval nodes in melanoma patients.
    • Subcellular distribution of the sodium iodide symporter in benign and malignant thyroid tissues.

      Kollecker, I; Von Wasielewski, R; Langner, C; Müller, J A; Spitzweg, C; Kreipe, H; Brabant, Georg E; Department of Pathology, Medical School of Hannover, Hannover, Germany. (2012-05)
      Membranous expression of the sodium iodide symporter (NIS) is a prerequisite for iodide uptake in thyrocytes. Previous studies reported heterogeneous results on the relative frequency of staining in various pathological conditions of the thyroid. The present study aimed at determining membranous staining by using confocal laser microscopy in benign and malignant thyroid diseases, complemented in a subgroup of patients with recurrent or metastatic disease with functional findings of radioiodine uptake (RIU).
    • Subcutaneous (SC) Epcoritamab (GEN3013; DuoBody-CD3xCD20) in patients with relapsed/refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL): dose-escalation data from a phase I/II Trial

      Hutchings, M.; Lugtenburg, P.; Mous, R.; Clausen, M. R.; Chamuleau, M.; Linton, Kim M; Rule, S.; Lopez, J.; Oliveri, R. S.; DeMarco, D.; et al. (2020)
      Context: CD3×CD20 bispecifi c antibodies (bsAbs) have demonstrated promising results in R/R B-NHL. Epcoritamab is a novel subcutaneously-administered bsAb with a favorable safety profi le and encouraging preliminary anti-tumor activity in both aggressive and indolent B-NHL in a Phase I/II trial (NCT03625037). Objective: Determine recommended phase 2 dose, safety, and anti-tumor activity of epcoritamab. Participants: Adults with R/R CD20+ B-NHL. Intervention: SC 1 mL injection of fl at-dose epcoritamab (dosing escalation range 0.0128–48 mg preceded by a priming and intermediate dose) administered in 28-day cycles until disease progression or unacceptable toxicity. Results: As of 24 April 2020, 58 patients with a median (range) age 68 (21–84) years were enrolled. Most patients had DLBCL (67.2%) or FL (19.0%) and received a median (range) of 3 (1–6) and 5 (1–18) prior lines of treatment, respectively. No dose-limiting toxicities were observed (median follow-up [range]: 2.7 [ 0.2–16.4] months). MTD has not been reached. Majority of TEAEs were mild (Grade 1–2); the most common TEAEs (>35%) were pyrexia (69.0%), fatigue (41.4%), and injection site reaction (41.4%; all Grade 1). AEs of special interest included CRS (56.9%; no Grade 3 events occurred; all resolved) and neurotoxicity (6.9%; median [range] duration of events: 1 [<1– 3] day). There was no tumor lysis syndrome, neutropenic fever, or treatment-related death. Treatment is ongoing in 20 patients. Antitumor activity (14 May 2020) in evaluable patients with DLBCL (12mg) and FL (0.76mg) are: DLBCL (n=15): ORR 60.0% (CR: 20.0%; PR: 40.0%), SD: 6.7%, PD: 33.3%. FL (n=7): ORR 85.7% (PR: 85.7%), SD: 14.3%, no patients with PD. One patient with DLBCL de novo achieved a response post-data cutoff. Median (range) time to response was 1.6 (1–4) months. Conclusions: The safety, effi cacy, and pharmacokinetics data support epcoritamab 48 mg SC (1 mL, single dose) to be explored in the expansion phase. SC epcoritamab continues to demonstrate a favorable safety profi le consistent with previous reported data. Notably, there were no treatment-related deaths, no febrile neutropenia, tumor lysis syndrome, or Grade 3 CRS events. Epcoritamab has the potential for outpatient administration. Epcoritamab induces rapid, deep responses in heavily pretreated patients across different B-NHL subtypes.
    • Subcutaneous (SC) epcoritamab induces complete responses across R/R B-cell NHL subtypes: Updated dose-escalation data

      Hutchings, M.; Mous, R.; Clausen, M. R.; Johnson, P.; Linton, Kim M; Chamuleau, M. E. D.; Lewis, D. J.; Balari, A. S.; Cunningham, D.; Oliveri, R. S.; et al. (2021)
      Background: Epcoritamab is a CD3CD20 bispecific antibody with a favorable safety profile and encouraging preliminary antitumor activity in both aggressive and indolent B-NHL in a phase I/II trial (NCT03625037). Updated dose-escalation data are reported here. Methods: Adults with R/R CD20+ B-NHL receive a SC 1 mL injection of flat-dose epcoritamab in 28-day cycles (q1w: cycles 1-2; q2w: cycles 3-6; q4w thereafter) until disease progression or unacceptable toxicity. Objectives include safety and antitumor activity. Results: As of 6 July 2020, 67 patients (pts) were enrolled (DLBCL, 67%; FL, 18%; MCL, 6%). Pts were heavily pretreated, with a median (range) of 3.0 (1-6) prior lines of therapy for DLBCL and 4.5 (1-18) for FL. A total of 6 pts received prior CAR-T therapy. At median follow-up of 8.3 months, treatment is ongoing in 25 pts (37%). Epcoritamab was generally well tolerated, with no discontinuations due to treatment-emergent adverse events (TEAEs). The most common TEAEs were pyrexia (70%), local injection-site reactions (48%), and fatigue (45%). Observed TEAEs of special interest were cytokine release syndrome (CRS; all events were Gr 1/2 [58%], no Gr 3/4) and limited neurotoxicities (Gr 1, 3%; Gr 3, 3%; all transient). There were no DLTs, febrile neutropenia events, or deaths due to TEAEs. In pts with DLBCL treated with epcoritamab 12 mg (n¼18), ORR was 66.7% (6 CR). For pts who received higher doses (48 mg [RP2D], n¼4; 60 mg, n¼3) ORR was 100% (2 CR, 5 PR). All 4 DLBCL pts with prior CAR-T therapy achieved a response (2 CR, 2 PR). In FL (epcoritamab 0.76 mg, n¼8), ORR was 100% (2 CR). Responses (1 CR,1 PR) were observed in 2/4 pts with blastoid variant MCL. Conclusions: Epcoritamab demonstrates a consistent, favorable safety profile, with no Gr 3 CRS events and limited neurotoxicity, in support of future outpatient administration. Emerging data are encouraging, including CR in heavily y pretreated pts with DLBCL, FL, and MCL.
    • Subcutaneous delivery of amivantamab in patients with advanced solid malignancies: PALOMA, an open-label, multicenter, dose escalation phase 1b study

      Krebs, Matthew G; Johnson, M. L.; Cho, B. C.; Park, K.; Haddish-Berhane, N.; Zemlickis, D.; Mitselos, A.; Meacle, F.; Knoblauch, R. E.; Hellemans, P.; et al. (2021)
      Background: Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody with immune cell-directing activity, targets activating/resistance EGFR mutations and MET mutations/amplifications. Amivantamab has demonstrated antitumor activity in patients (pts) with EGFR-mutant NSCLC and also in pts with EGFR tyrosine kinase inhibitor-resistant disease. The recommended phase 2 dose (RP2D) is 1050 mg (1400 mg, ≥80 kg) administered as intravenous (IV) infusions weekly (QW) for the first 28-day cycle and every other week (Q2W) thereafter. A subcutaneous (SC) formulation of amivantamab has the potential to reduce pt and physician burden by reducing administration time. The safety and pharmacokinetics (PK) of amivantamab administered SC ± recombinant human hyaluronidase (rHuPH20) will be evaluated. Methods: PALOMA is an ongoing phase 1b dose escalation study of amivantamab SC in pts with advanced solid tumors that may derive benefit from EGFR or MET-directed therapy (NCT04606381). Pts must have progressed on standard of care therapy for metastatic disease, be ineligible for, or have refused current standard therapies. The primary endpoints are trough concentration at the end of QW dosing and safety of SC administration. The objective of part 1 is to evaluate the feasibility, safety, and PK of SC administration of a low concentration (50 mg/mL) formulation of amivantamab alone (Ami-LC) or admixed with rHuPH20 (Ami-LC-MD). Approximately 8 pts will be enrolled to receive either 1050/1400 mg amivantamab SC using Ami-LC-MD (Cohort 1a) or Ami-LC (Cohort 1b) QW in cycle 1 and Q2W thereafter. The objective of part 2 is to evaluate the safety and PK of SC administration of a high concentration (160 mg/mL) formulation of amivantamab alone (Ami-HC) or with rHuPH20 (Ami-HC-CF) and to determine a dose, schedule, and formulation for SC administration that achieves similar exposure as observed at the RP2D of amivantamab IV, with acceptable safety. Pts enrolled in part 2 will initially receive 1050/1400 mg amivantamab SC using Ami-HC-CF in Cohort 2a or Ami-HC in Cohort 2b. ≤10 pts may be enrolled in either cohort. Additional cohorts of ≤10 pts may be enrolled to support dose, schedule, and formulation selection as guided by safety and PK observations in earlier cohorts. To mitigate infusion related reactions (IRR), medication with steroid, paracetamol, and antihistamine will be given pre-infusion and as clinically indicated post-infusion. Safety assessments include monitoring adverse events, laboratory abnormalities, vital signs, IRR, and injection site reactions. Blood samples will be collected to assess PK, pharmacodynamics, and immunogenicity. A Study Evaluation Team composed of investigators and sponsor representatives will review safety and PK data to make decisions about dose escalation and cohort expansion throughout the conduct of the study.
    • Subcutaneous epcoritamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Safety profile and antitumor activity

      Clausen, M. R.; Lugtenburg, P.; Hutchings, M.; Johnson, P. W. M.; Linton, Kim M; Lewis, D. J.; Chamuleau, M.; Balari, A. S.; Cunningham, D.; Elliott, B.; et al. (2021)
      Background: Epcoritamab is a CD20xCD3 bispecific antibody that induces T-cell mediated killing of CD20–positive malignant B-cells. We present updated data, including progression-free survival (PFS) from the dose escalation part of the first-in-human phase 1/2 study of epcoritamab in pts with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT03625037). Methods: Adults with R/R CD20+ B-NHL received flat-dose 1 mL SC epcoritamab (step-up dosing approach) in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Step-up dosing and standard prophylaxis were used to mitigate severity of cytokine release syndrome (CRS). Results: At data cut off (1/31/2021), 68 pts with B-NHL were enrolled across histologies including diffuse large B-cell lymphoma (DLBCL; n = 46 [67.6%]; de novo and transformed), follicular lymphoma (FL; 12 [17.6%]), mantle cell lymphoma (MCL; 4 [5.9%]), and others (6 [8.8%]). Majority were heavily pretreated (median [range] prior lines: DLBCL, 3 [1–6]; FL, 4.5 [1–18]); including prior CAR-T (n = 6) and prior ASCT (n = 10). At median follow-up of 14.1 mo (DLBCL, 10.2 mo; FL, 15.2 mo), treatment was ongoing in 15 (22%) pts. Most common treatment-emergent adverse events (AEs) were pyrexia (69%), CRS (59%), and injection site reaction (47%). CRS events were all grade 1 or 2 and most occurred in cycle 1; neurotoxicity was limited (6%; grade 1: 3%; grade 3: 3%; all transient). One case of tumor lysis syndrome was observed (1.5%; grade 3); there were no cases of febrile neutropenia or treatment-related death. Overall response is shown for DLBCL ≥12 mg and ≥48 mg and FL ≥12 mg, corresponding to the minimal efficacy threshold (Table). Responses deepened over time (PR converted to CR: DLBCL, 6 pts; FL, 3 pts). Median time to response was 1.4 mo (DLBCL) and 1.9 mo (FL). Among DLBCL pts achieving CR with ≥6 mg (n = 11), none relapsed while on treatment. The median PFS for pts with DLBCL ≥12 mg (n = 22) was 9.1 mo (95% CI: 1.6, NE; median follow-up 9.3 mo) and for pts with DLBCL ≥48 mg (n = 11) median PFS was not reached (median follow-up 8.8 mo). Updated analyses will be presented. Conclusions: With longer follow-up, SC epcoritamab demonstrated substantial single-agent activity, inducing deep and durable clinically meaningful responses, with a consistent safety profile. Notably no severe (grade ≥3) CRS events, no febrile neutropenia, and limited neurotoxicity was observed.
    • Subcutaneous T-cell lymphoma with florid granulomatous panniculitis.

      Prescott, R J; Banerjee, Saumitra S; Cross, P A; Department of Histopathology, Christie Hospital, Holt Radium Institute, Manchester, UK. (1992-06)
    • Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study.

      Moreau, P; Pylypenko, H; Grosicki, S; Karamanesht, L; Leleu, X; Grishunina, M; Rekhtman, G; Masliak, Z; Robak, T; Shubina, A; et al. (2011-05)
      Intravenous injection is the standard administration route of bortezomib; however, subcutaneous administration is an important alternative. We compared the efficacy and safety of subcutaneous versus intravenous bortezomib at the approved 1·3 mg/m(2) dose and twice per week schedule in patients with relapsed multiple myeloma.
    • Subgroup analysis of rucaparib in platinum-sensitive recurrent ovarian carcinoma: effect of prior chemotherapy regimens in ARIEL3

      Lorusso, D; Coleman, RL; Oza, AM; Aghajanian, C; Oaknin, A; Dean, A; Colombo, N; Weberpals, JI; Clamp, Andrew R; Scambia, G; et al. (2018)
    • Submandibular gland carcinoma; an audit of local control and survival following adjuvant radiotherapy.

      Sykes, Andrew J; Slevin, Nicholas J; Birzgalis, Andrew R; Gupta, Nirmal K; Christie Hospital NHS Trust, Holt Radium Institute, Manchester, UK. (1999-03)
      Carcinoma of the submandibular gland is a rare diagnosis, accounting for less than 2% of cases of salivary gland tumours. We have examined the treatment and outcome of a total of 30 patients treated with radiotherapy at the Christie Hospital, Manchester between 1980 and 1993. In most cases this followed radical surgery, though 12 patients were referred following either incomplete excision or biopsy only. Adenoid-cystic histology accounted for 19 cases (63%). Standard radiotherapy was delivered using a beam directed technique to treat the whole submandibular compartment. Doses prescribed were most commonly from 50 to 55 Gy in 16 fractions over three weeks. Cancer specific survival was 79% and 57% at 5 and 10 yr respectively, the continued fall at 10 yr reflected late recurrence seen in patients with adenoid-cystic histology. Local control was 85% and 73%, respectively. Nine of twelve patients with incomplete excision or biopsy only had local control with radiotherapy. Six patients developed lung metastases, all of whom had adenoid-cystic histology. Radiotherapy was well-tolerated acutely, and only one patient experienced osteoradionecrosis requiring surgical intervention. The incidence of adenoid-cystic carcinoma is higher in the submandibular than the parotid gland. This typically results in late recurrence, and a high incidence of lung metastases and this was confirmed in our study. However, overall survival was very similar to that of parotid carcinoma.
    • A subnormal peak cortisol response to stimulation testing does not predict a subnormal cortisol production rate.

      Paisley, Angela N; Rowles, Susannah V; Brandon, D; Trainer, Peter J; Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom. (2009-05)
      INTRODUCTION: The decision to commence lifelong glucocorticoid replacement therapy is often based on a cortisol stimulation test. We investigated the relationship between the peak cortisol response to insulin-induced hypoglycemia and daily cortisol production rate (CPR) to ascertain whether provocative tests are accurate in indicating the need to initiate lifelong glucocorticoid replacement. PATIENTS AND METHODS: Ten patients (five male; mean age, 44 +/- 13 yr) with pituitary disease and with demonstrably suboptimal peak cortisol response (350-500 nmol/liter) to insulin-induced hypoglycemia, underwent CPR measurement by isotope dilution using gas chromatography-mass spectrometry and 24-h urinary free cortisol (UFC). RESULTS: The median baseline and peak cortisol attained with hypoglycemia were 284 (164-323) and 473.5 (366-494) nmol/liter, respectively. A strong positive correlation was seen between peak stimulated cortisol and CPR (adjusted for body surface area) (r = 0.75; P = 0.02), and in all patients CPR [4.6 (2.9-15.1) mg/d x m(2)] was within the reference range (2.1-12 mg/d x m(2)) or elevated (one patient). A wide range was found for 24-h UFC [116.5 (20.5-265.9) nmol/liter] in this group of patients, and this parameter lacked significant correlation with either serum cortisol concentration or CPR. CONCLUSION: This is the first study to demonstrate a significant correlation between CPR and peak cortisol values during hypoglycemic challenge. An inadequate cortisol response to hypoglycemia suggests the need for glucocorticoid cover at times of stress, but these data indicate that a suboptimal peak cortisol does not equate to a low CPR and should not be an automatic indication for lifelong glucocorticoid replacement therapy. UFC bears no relation to serum cortisol or CPR and is therefore unhelpful in assessment of such patients.
    • Suboptimal use of intravenous contrast during radiotherapy planning in the UK.

      Kim, Su Woon; Russell, Wanda; Price, Patricia M; Saleem, Azeem; Department of Clinical Oncology, Christie Hospital, Manchester, UK. (2008-12)
      We aimed to evaluate the use of intravenous (IV) contrast during acquisition of radiotherapy planning (RTP) scans and to compare current usage with the Royal College of Radiologists' (RCR) recommendations. Questionnaires were circulated via the Academic Clinical Oncology and Radiobiology Research Network (ACORRN) website, email and post to 60 UK radiotherapy centre managers. Questions were asked regarding the (i) tumour sites where IV contrast was used, (ii) person administering the contrast, (iii) availability of dynamic pump, (iv) tumour sites that centres wished to use contrast, (v) reasons for not using contrast and (vi) awareness of RCR recommendations. 50 (83%) centres responded to the questionnaire, of which 27 responded via the ACCORN website and 18 by e-mail. Despite 38 out of 50 responding centres using IV contrast, and accessibility to dynamic pumps existing in 39 centres, IV contrast usage was suboptimal, with more than half of the centres (27/50; 54%) wishing to use it at more tumour sites. IV contrast was most often used during RTP of the brain, with suboptimal usage in lung tumours. None of the 50 centres administered IV contrast during RTP scan acquisition in all of the 8 RCR recommended tumour sites. Radiographers were mainly responsible for contrast administration, and a lack of staff was cited as the main reason for suboptimal contrast usage. Disappointingly, only 35 of the 50 radiotherapy managers (70%) were aware of the RCR recommendations. Redress of the underlying reasons for suboptimal IV contrast administration during RTP, including acquisition of the necessary skill mix by staff and implementation of RCR recommendations, would help standardize UK practice.
    • Subregional analysis of the parotid glands: predicting late xerostomia in head and neck cancer

      Berger, T.; Noble, D. J.; Shelley, L. E.; McMullan, T.; Romanchikova, M.; Carruthers, L. J.; Cebamanos, L.; Beckett, G.; Duffton, A.; Paterson, C.; et al. (2020)
      Several studies have investigated the relationship between the clinical symptoms of xerostomia and the radiotherapy dose received by subregions of the parotid glands (e.g. superficial lobe/stem cell region). The purpose of this study was to compare the predictive power of image biomarkers (IMB) calculated on the superficial lobe (SL), deep lobe (DL) and whole parotid (WP) gland for identifying late xerostomia in head and neck (H&N) cancer patients. Material and Methods All patients (N=60) received 30 fractions (fx) on a TomoTherapy HiArt System (Accuray, Sunnyvale, CA, USA) with daily mega-voltage CT (MVCT) images with CTCAE toxicity recorded at 12 months. As illustrated in Figure 1, the MVCT images (0.76 x 0.76 x 6 mm) were used to calculate by textural analysis, seventy-three IMBs consisting of first and higher order features on the SL, DL and WP gland. For each feature, their values for the period 1-20fx were used to perform linear regressions and their slopes considered as potential predictors. LASSO analysis was used (100 times) with 4-fold cross validation to select the best predictors (<9) for each region. To evaluate the robustness of each of the 100 combinations, the patients were split into four folds. The training set made up of 3 folds and the testing set, the remaining fold, were used to test the predictive power of each of the LASSO combinations using a logistic regression model. This was evaluated by the Area Under the Curve (AUC), resulting in 4 AUCtest and 4 AUCtrain values which were averaged (mAUCtest and mAUCtrain). For robustness, this process was repeated 100 times for each combination of predictors and the median mAUCtest and mAUCtrain calculated. The 50 combinations of predictors with the highest median mAUC were selected for the SL, DL and WP and their median mAUCtest distributions compared using a t-test. Results Of the 60 patients, 27% reported xerostomia (grade>1) at 12 months. The highest median mAUCtrain / mAUCtest were 0.93/0.83, 0.90/0.79 and 0.93/0.80 for the SL, DL and WP, respectively. As shown in Figure 2, the 50 combinations of predictors that were selected for the WP gland yielded a significantly higher median mAUCtest compared to the DL (p<0.01). The selected combinations of the SL yielded higher median mAUCtest compared to the WP (p<0.01). Conclusion The slopes of the IMBs extracted from the DL (from fraction 1-20) have a lower predictive power compared to those extracted from the WP gland. Despite the smaller number of voxels considered when analyzing the SL, the IMBs extracted from the SL have a higher predictive power compared to those from the WP. However, this requires further validation on a larger cohort and different selected periods. To obtain a greater understanding of the differences in predictive power of each of these subregions requires further information on the underlying biological processes.