Citation: British Journal of Dermatology. 2019, 181, 136
Author: Yip V.; Olsson-Brown A.; Pirmohamed M.; Hindle E.
Abstract: Immune checkpoint inhibitors (ICIs) are immunomodulatory agents used in the treatment of an increasing number of malignancies. They inhibit tumour-induced immunosuppression and reactivate tumour-specific cytotoxic T lymphocytes resulting in control of malignant disease (Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 25264). However, off-target tissue effects can lead to immune-related adverse effects (irAEs), most commonly in the skin (Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol 2018; 19: 34561). From May 2014 to July 2018, all cases of immunotherapy-induced cutaneous irAEs referred to a specialist dermatology unit were reviewed. Demographics, clinical features, investigations and outcomes for patients were recorded. Sixteen patients were referred with ICI-induced cutaneous toxicity. Nine (56%) were female and seven (44%) male. Their mean age was 67.8 years (range 4881). The mean time to reaction was 3.6 months after starting ICI treatment (range 18). Melanoma (n = 11) was the most common indication for ICI therapy, followed by nonsmall-cell lung cancer (n = 5). Eleven patients experienced irAEs secondary to pembrolizumab, three to combination ipilimumab/nivolumab therapy and one to ipilimumab and nivolumab, respectively. The most common cutaneous irAEs were eczema (n = 9) and lichenoid reactions (n = 3). Individual cases of psoriasis, inflammatory rash, petechiae and telogen effluvium were reported. No cases of severe cutaneous adverse reactions (e.g. tevensJohnson syndrome) were reported. Treatment with oral (n = 9) or topical (n = 4) corticosteroids was most often prescribed. Intravenous corticosteroids, combination topical corticosteroidantiinfective, acitretin and methotrexate were prescribed to individual patients. Eight patients required a protracted course of treatment. Cutaneous toxicities resulted in discontinuation of ICI therapy in one patient
and delayed treatment in two cases, and led to modification of combination therapy in one case. Cutaneous irAEs most commonly manifested as an itchy erythematous rash clinically consistent with eczema. Corticosteroids were required in the majority of cases. In some cases, cutaneous irAEs resulted in delay or discontinuation of ICI therapy. As ICI usage expands, cutaneous adverse events will become an increasing issue, requiring further research to elucidate pathogenic mechanisms in order to improve clinical management.
Thursday 29 August 2019
CCC publication: Patient Reported Acute Toxicity in PACE-B, an International Phase III Randomised Controlled Trial Comparing Stereotactic Body Radiotherapy to Conventionally Fractionated or Moderately Hypofractionated Radiotherapy (CFMHRT) for Localised Prostate Cancer
Citation: International Journal of Radiation Oncology Biology Physics. 2019, 105(1)
Author: Brand D.H.; Tree A.; Morrison K.; Naismith O.; van As N.; Ostler P.; van der Voet H.; Loblaw D.A.; Chu W.; Ford D.;Tolan S.; Jain S.; Martin A.; Staffurth J.; Brown S.; Burnett S.; Griffin C.; Hinder V.; Hall E.; Duffton A.
Abstract: Purpose/Objective(s): External beam radiotherapy (EBRT) is one of several curative treatment options for localised prostate cancer (LPCa). Moderate hypofractionation of EBRT (2.5-3Gy per fraction (f)) has been shown non-inferior to conventional 2 Gy/f by multiple large randomised controlled trials (RCTs). Low and comparable rates of clinician reported acute toxicity have been reported in the Stereotactic Body Radiotherapy (SBRT) and CFMHRT treated groups in PACE-B. This study reports patient reported outcomes (PRO) for
bladder and bowel, related to acute toxicity. Materials/Methods: PACE (NCT01584258) is a phase III, openlabel, multiple-cohort RCT. Patients eligible for the PACE-B cohort had LPCa, stage T1-T2, <= Gleason 3 + 4, PSA <= 20 ng/mL and were either unsuitable for surgery or chose EBRT. Randomisation was 1:1 between SBRT (36.25Gy/5f over 1-2 weeks (wks)) or CFMHRT (78Gy/39f over 7.5 wks or 62Gy/20f over 4 wks, determined by centre's standard schedule). Androgen deprivation therapy was not allowed. PRO metrics included: Expanded Prostate Cancer Index Composite 26 (EPIC-26) at baseline, 2, 4, 12 wks post radiotherapy (RT); International Prostate Symptom Score (IPSS) at baseline, 2, 4, 8, 12 wks post-RT. The proportion of patients with EPIC-26 change scores (baseline to 12 wks) greater than minimum clinically important differences (MCID) in each subdomain (urinary incontinence (UI) 8 points, urinary obstructive (UO) 6 points, bowel 5 points) are reported. IPSS total scores were categorised as none, mild, moderate, severe and compared between SBRT and CFMHRT at 12 weeks. Comparisons between SBRT and CFMHRT were based on chi-squared tests with p < 0.01 considered statistically significant.
Result(s): Between 07/12/2012 and 04/01/18, 38 centres randomised 874 pts: 431 received CFMHRT; 414 SBRT. Patient and disease characteristics were similar between CFMHRT and SBRT: mean age: 69.5 vs 69.3 years; Intermediate risk: 91.4% vs 92.5%; T-stage >=T2b: 51.7% vs 56.6%; Gleason Score 3+4: 80.7% vs 85.5%; PSA 10-20 ng/mL: 30.9% vs 31.6%. EPIC MCID deteriorations, for CFMHRT vs SBRT, occurring by subdomain were: UI 67/326 (20.6%) vs 51/323 (15.8%), p=0.12; UO 108/313 (34.5%) vs 105/306 (34.3%), p=0.96; bowel
91/322 (28.2%) vs 90/323 (27.9%), p=0.91. Proportion of patients with baseline none/mild/moderate/severe IPSS symptoms were CFMHRT: 5.4%/51.1%/37.3%/6.2% and SBRT: 4.5%/54.5%/35.6%/5.4%. At 12 weeks no differences were seen in IPSS scores between CFMHRT and SBRT: 2.8%/57.9%/36.8%/2.5% vs 3.4%/54.8%/36.7%/5.1% (p=0.34, test for trend).
Conclusion(s): These data corroborate the prior clinician-reported acute toxicity findings for bladder and bowel outcomes, with no significant differences in key PRO measures.
Copyright © 2019
Author: Brand D.H.; Tree A.; Morrison K.; Naismith O.; van As N.; Ostler P.; van der Voet H.; Loblaw D.A.; Chu W.; Ford D.;Tolan S.; Jain S.; Martin A.; Staffurth J.; Brown S.; Burnett S.; Griffin C.; Hinder V.; Hall E.; Duffton A.
Abstract: Purpose/Objective(s): External beam radiotherapy (EBRT) is one of several curative treatment options for localised prostate cancer (LPCa). Moderate hypofractionation of EBRT (2.5-3Gy per fraction (f)) has been shown non-inferior to conventional 2 Gy/f by multiple large randomised controlled trials (RCTs). Low and comparable rates of clinician reported acute toxicity have been reported in the Stereotactic Body Radiotherapy (SBRT) and CFMHRT treated groups in PACE-B. This study reports patient reported outcomes (PRO) for
bladder and bowel, related to acute toxicity. Materials/Methods: PACE (NCT01584258) is a phase III, openlabel, multiple-cohort RCT. Patients eligible for the PACE-B cohort had LPCa, stage T1-T2, <= Gleason 3 + 4, PSA <= 20 ng/mL and were either unsuitable for surgery or chose EBRT. Randomisation was 1:1 between SBRT (36.25Gy/5f over 1-2 weeks (wks)) or CFMHRT (78Gy/39f over 7.5 wks or 62Gy/20f over 4 wks, determined by centre's standard schedule). Androgen deprivation therapy was not allowed. PRO metrics included: Expanded Prostate Cancer Index Composite 26 (EPIC-26) at baseline, 2, 4, 12 wks post radiotherapy (RT); International Prostate Symptom Score (IPSS) at baseline, 2, 4, 8, 12 wks post-RT. The proportion of patients with EPIC-26 change scores (baseline to 12 wks) greater than minimum clinically important differences (MCID) in each subdomain (urinary incontinence (UI) 8 points, urinary obstructive (UO) 6 points, bowel 5 points) are reported. IPSS total scores were categorised as none, mild, moderate, severe and compared between SBRT and CFMHRT at 12 weeks. Comparisons between SBRT and CFMHRT were based on chi-squared tests with p < 0.01 considered statistically significant.
Result(s): Between 07/12/2012 and 04/01/18, 38 centres randomised 874 pts: 431 received CFMHRT; 414 SBRT. Patient and disease characteristics were similar between CFMHRT and SBRT: mean age: 69.5 vs 69.3 years; Intermediate risk: 91.4% vs 92.5%; T-stage >=T2b: 51.7% vs 56.6%; Gleason Score 3+4: 80.7% vs 85.5%; PSA 10-20 ng/mL: 30.9% vs 31.6%. EPIC MCID deteriorations, for CFMHRT vs SBRT, occurring by subdomain were: UI 67/326 (20.6%) vs 51/323 (15.8%), p=0.12; UO 108/313 (34.5%) vs 105/306 (34.3%), p=0.96; bowel
91/322 (28.2%) vs 90/323 (27.9%), p=0.91. Proportion of patients with baseline none/mild/moderate/severe IPSS symptoms were CFMHRT: 5.4%/51.1%/37.3%/6.2% and SBRT: 4.5%/54.5%/35.6%/5.4%. At 12 weeks no differences were seen in IPSS scores between CFMHRT and SBRT: 2.8%/57.9%/36.8%/2.5% vs 3.4%/54.8%/36.7%/5.1% (p=0.34, test for trend).
Conclusion(s): These data corroborate the prior clinician-reported acute toxicity findings for bladder and bowel outcomes, with no significant differences in key PRO measures.
Copyright © 2019
Wednesday 28 August 2019
CCC publication: Pharmacodynamic and Clinical Results from a Phase I/II Study of the HSP90 Inhibitor Onalespib in Combination with Abiraterone Acetate in Prostate Cancer
Citation: Clinical Cancer Research. 2019, 25(15), 4624-633
Author: Slovin, Susan; Hussain, Syed; Saad, Fred; Garcia, Jorge; Picus, Joel; Ferraldeschi, Roberta; Crespo, Mateus; Flohr,
Abstract: PURPOSE: Onalespib is a potent, fragment-derived second-generation HSP90 inhibitor with preclinical activity in castration-resistant prostate cancer (CPRC) models. This phase I/II trial evaluated onalespib in combination with abiraterone acetate (AA) and either prednisone or prednisolone (P) in men with CRPC progressing on AA/P.
PATIENTS AND METHODS: Patients with progressing CRPC were randomly assigned to receive 1 of 2 regimens of onalespib combined with AA/P. Onalespib was administered as intravenous infusion starting at 220 mg/m2 once weekly for 3 of 4 weeks (regimen 1); or at 120 mg/m2 on day 1 and day 2 weekly for 3 of 4 weeks (regimen 2). Primary endpoints were response rate and safety. Secondary endpoints included evaluation of androgen receptor (AR) depletion in circulating tumor cells (CTC) and in fresh tumor tissue biopsies.
RESULTS: Forty-eight patients were treated with onalespib in combination with AA/P. The most common ≥grade 3 toxicities related to onalespib included diarrhea (21%) and fatigue (13%). Diarrhea was dose limiting at 260 and 160 mg/m2 for regimens 1 and 2, respectively. Transient decreases in CTC counts and AR expression in CTC were observed in both regimens. HSP72 was significantly upregulated following onalespib treatment, but only a modest decrease in AR and GR was shown in paired pre- and posttreatment tumor biopsy samples. No patients showed an objective or PSA response.
CONCLUSIONS: Onalespib in combination with AA/P showed mild evidence of some biological effect; however, this effect did not translate into clinical activity, hence further exploration of this combination was not justified.
©2019 American Association for Cancer Research.
Link to PubMed record
Author: Slovin, Susan; Hussain, Syed; Saad, Fred; Garcia, Jorge; Picus, Joel; Ferraldeschi, Roberta; Crespo, Mateus; Flohr,
Abstract: PURPOSE: Onalespib is a potent, fragment-derived second-generation HSP90 inhibitor with preclinical activity in castration-resistant prostate cancer (CPRC) models. This phase I/II trial evaluated onalespib in combination with abiraterone acetate (AA) and either prednisone or prednisolone (P) in men with CRPC progressing on AA/P.
PATIENTS AND METHODS: Patients with progressing CRPC were randomly assigned to receive 1 of 2 regimens of onalespib combined with AA/P. Onalespib was administered as intravenous infusion starting at 220 mg/m2 once weekly for 3 of 4 weeks (regimen 1); or at 120 mg/m2 on day 1 and day 2 weekly for 3 of 4 weeks (regimen 2). Primary endpoints were response rate and safety. Secondary endpoints included evaluation of androgen receptor (AR) depletion in circulating tumor cells (CTC) and in fresh tumor tissue biopsies.
RESULTS: Forty-eight patients were treated with onalespib in combination with AA/P. The most common ≥grade 3 toxicities related to onalespib included diarrhea (21%) and fatigue (13%). Diarrhea was dose limiting at 260 and 160 mg/m2 for regimens 1 and 2, respectively. Transient decreases in CTC counts and AR expression in CTC were observed in both regimens. HSP72 was significantly upregulated following onalespib treatment, but only a modest decrease in AR and GR was shown in paired pre- and posttreatment tumor biopsy samples. No patients showed an objective or PSA response.
CONCLUSIONS: Onalespib in combination with AA/P showed mild evidence of some biological effect; however, this effect did not translate into clinical activity, hence further exploration of this combination was not justified.
©2019 American Association for Cancer Research.
Link to PubMed record
CCC publication: Chemoradiotherapy of locally-advanced non-small cell lung cancer: Analysis of radiation dose-response, chemotherapy and survival-limiting toxicity effects indicates a low α/β ratio
Citation: Radiotherapy and Oncology. 2019 Aug 19. [Epub ahead of print]
Author: Michael G. Nix, Carl G. Rowbottom, Sindu Vivekanandan, Maria A. Hawkins, John D. Fenwick,
Abstract: PURPOSE: To analyse changes in 2-year overall survival (OS2yr) with radiotherapy (RT) dose, dose-per-fraction, treatment duration and chemotherapy use, in data compiled from prospective trials of RT and chemo-RT (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC).
MATERIAL AND METHODS: OS2yr data was analysed for 6957 patients treated on 68 trial arms (21 RT-only, 27 sequential CRT, 20 concurrent CRT) delivering doses-per-fraction ≤4.0 Gy. An initial model considering dose, dose-per-fraction and RT duration was fitted using maximum-likelihood techniques. Model extensions describing chemotherapy effects and survival-limiting toxicity at high doses were assessed using likelihood-ratio testing, the Akaike Information Criterion (AIC) and cross-validation.
RESULTS: A model including chemotherapy effects and survival-limiting toxicity described the data significantly better than simpler models (p < 10-14), and had better AIC and cross-validation scores. The fitted α/β ratio for LA-NSCLC was 4.0 Gy (95%CI: 2.8-6.0 Gy), repopulation negated 0.38 (95%CI: 0.31-0.47) Gy EQD2/day beyond day 12 of RT, and concurrent CRT increased the effective tumour EQD2 by 23% (95%CI: 16-31%). For schedules delivered in 2 Gy fractions over 40 days, maximum modelled OS2yr for RT was 52% and 38% for stages IIIA and IIIB NSCLC respectively, rising to 59% and 42% for CRT. These survival rates required 80 and 87 Gy (RT or sequential CRT) and 67 and 73 Gy (concurrent CRT). Modelled OS2yr rates fell at higher doses.
CONCLUSIONS: Fitted dose-response curves indicate that gains of ~10% in OS2yr can be made by escalating RT and sequential CRT beyond 64 Gy, with smaller gains for concurrent CRT. Schedule acceleration achieved via hypofractionation potentially offers an additional 5-10% improvement in OS2yr. Further 10-20% OS2yr gains might be made, according to the model fit, if critical normal structures in which survival-limiting toxicities arise can be identified and selectively spared.
Copyright © 2019 Elsevier B.V. All rights reserved.
KEYWORDS: Chemotherapy; Dose-escalation; NSCLC; Radiotherapy; Toxicity
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Author: Michael G. Nix, Carl G. Rowbottom, Sindu Vivekanandan, Maria A. Hawkins, John D. Fenwick,
Abstract: PURPOSE: To analyse changes in 2-year overall survival (OS2yr) with radiotherapy (RT) dose, dose-per-fraction, treatment duration and chemotherapy use, in data compiled from prospective trials of RT and chemo-RT (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC).
MATERIAL AND METHODS: OS2yr data was analysed for 6957 patients treated on 68 trial arms (21 RT-only, 27 sequential CRT, 20 concurrent CRT) delivering doses-per-fraction ≤4.0 Gy. An initial model considering dose, dose-per-fraction and RT duration was fitted using maximum-likelihood techniques. Model extensions describing chemotherapy effects and survival-limiting toxicity at high doses were assessed using likelihood-ratio testing, the Akaike Information Criterion (AIC) and cross-validation.
RESULTS: A model including chemotherapy effects and survival-limiting toxicity described the data significantly better than simpler models (p < 10-14), and had better AIC and cross-validation scores. The fitted α/β ratio for LA-NSCLC was 4.0 Gy (95%CI: 2.8-6.0 Gy), repopulation negated 0.38 (95%CI: 0.31-0.47) Gy EQD2/day beyond day 12 of RT, and concurrent CRT increased the effective tumour EQD2 by 23% (95%CI: 16-31%). For schedules delivered in 2 Gy fractions over 40 days, maximum modelled OS2yr for RT was 52% and 38% for stages IIIA and IIIB NSCLC respectively, rising to 59% and 42% for CRT. These survival rates required 80 and 87 Gy (RT or sequential CRT) and 67 and 73 Gy (concurrent CRT). Modelled OS2yr rates fell at higher doses.
CONCLUSIONS: Fitted dose-response curves indicate that gains of ~10% in OS2yr can be made by escalating RT and sequential CRT beyond 64 Gy, with smaller gains for concurrent CRT. Schedule acceleration achieved via hypofractionation potentially offers an additional 5-10% improvement in OS2yr. Further 10-20% OS2yr gains might be made, according to the model fit, if critical normal structures in which survival-limiting toxicities arise can be identified and selectively spared.
Copyright © 2019 Elsevier B.V. All rights reserved.
KEYWORDS: Chemotherapy; Dose-escalation; NSCLC; Radiotherapy; Toxicity
Link to PubMed record
CCC publication: Surgical management of large abdominal wall fibromatosis during pregnancy
Citation: BMJ Case reports. 2019, 12(7), e227811
Author: Sutton, Paul Anthony; Rooney, Paul; Ali, Nasim; Chandrasekar, Coonoor R
Abstract: KEYWORDS: general surgery; orthopaedic and trauma surgery; plastic and reconstructive surgery
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Author: Sutton, Paul Anthony; Rooney, Paul; Ali, Nasim; Chandrasekar, Coonoor R
Abstract: KEYWORDS: general surgery; orthopaedic and trauma surgery; plastic and reconstructive surgery
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CCC publication: The Breast Cancer Trainees Research Collaborative Group: A New Multidisciplinary Network to Facilitate Breast Cancer Research
Citation: Clinical Oncology. 2020, 32(1), e16-e18. 2019 Jul 26. [Epub ahead of print]
Author: V.W.T. Cheng, A. Heetun, T. Robinson, C.E. Coles, C. Palmieri, D. Rea, E.R. Copson,
Link to PubMed record
Author: V.W.T. Cheng, A. Heetun, T. Robinson, C.E. Coles, C. Palmieri, D. Rea, E.R. Copson,
Link to PubMed record
CCC publication: Characterisation of Deubiquitylating Enzymes in the Cellular Response to High-LET Ionizing Radiation and Complex DNA Damage
Citation: International Journal of Radiation Oncology, Biology, Physics. 2019, 104(3), 656-65
Author: Rachel J. Carter, Catherine M. Nickson, James M. Thompson, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons,
Abstract: PURPOSE: Ionizing radiation, particular high-linear energy transfer (LET) radiation, can induce complex DNA damage (CDD) wherein 2 or more DNA lesions are induced in close proximity, which contributes significantly to the cell killing effects. However, knowledge of the enzymes and mechanisms involved in coordinating the recognition and processing of CDD in cellular DNA are currently lacking.
METHODS AND MATERIALS: A small interfering RNA screen of deubiquitylation enzymes was conducted in HeLa cells irradiated with high-LET α-particles or protons, versus low-LET protons and x-rays, and cell survival was monitored by clonogenic assays. Candidates whose depletion led to decreased cell survival specifically in response to high-LET radiation were validated in both HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells, and the association with CDD repair was confirmed using an enzyme modified neutral comet assay.
RESULTS: Depletion of USP6 decreased cell survival specifically after high-LET α-particles and protons, but not low-LET protons or x-rays. USP6 depletion caused cell cycle arrest and a deficiency in CDD repair mediated through instability of poly(ADP-ribose) polymerase-1 (PARP-1) protein. Increased radiosensitivity of cells to high-LET protons as a consequence of defective CDD repair was furthermore mimicked using the PARP inhibitor olaparib, and through PARP-1 small interfering RNA.
CONCLUSIONS: USP6 controls cell survival in response to high-LET radiation by stabilizing PARP-1 protein levels, which is essential for CDD repair. We also describe synergy between CDD induced by high-LET protons and PARP inhibition, or PARP-1 depletion, in effective cancer cell killing.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Link to PubMed record
Author: Rachel J. Carter, Catherine M. Nickson, James M. Thompson, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons,
Abstract: PURPOSE: Ionizing radiation, particular high-linear energy transfer (LET) radiation, can induce complex DNA damage (CDD) wherein 2 or more DNA lesions are induced in close proximity, which contributes significantly to the cell killing effects. However, knowledge of the enzymes and mechanisms involved in coordinating the recognition and processing of CDD in cellular DNA are currently lacking.
METHODS AND MATERIALS: A small interfering RNA screen of deubiquitylation enzymes was conducted in HeLa cells irradiated with high-LET α-particles or protons, versus low-LET protons and x-rays, and cell survival was monitored by clonogenic assays. Candidates whose depletion led to decreased cell survival specifically in response to high-LET radiation were validated in both HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells, and the association with CDD repair was confirmed using an enzyme modified neutral comet assay.
RESULTS: Depletion of USP6 decreased cell survival specifically after high-LET α-particles and protons, but not low-LET protons or x-rays. USP6 depletion caused cell cycle arrest and a deficiency in CDD repair mediated through instability of poly(ADP-ribose) polymerase-1 (PARP-1) protein. Increased radiosensitivity of cells to high-LET protons as a consequence of defective CDD repair was furthermore mimicked using the PARP inhibitor olaparib, and through PARP-1 small interfering RNA.
CONCLUSIONS: USP6 controls cell survival in response to high-LET radiation by stabilizing PARP-1 protein levels, which is essential for CDD repair. We also describe synergy between CDD induced by high-LET protons and PARP inhibition, or PARP-1 depletion, in effective cancer cell killing.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Link to PubMed record
CCC publication: Forward- and Inverse-Planned Intensity-Modulated Radiotherapy in the CHHiP Trial: A Comparison of Dosimetry and Normal Tissue Toxicity
Citation: Clinical Oncology. 2019, 31(9), 600-10
Author: O.F. Naismith, C. Griffin, I. Syndikus, C. South, H. Mayles, P. Mayles, V. Khoo, C. Scrase, J. Graham, S. Hassan, E. Hall, D.P. Dearnaley,
Abstract: AIMS: The CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose-volume histogram and toxicity data were compared to explore the effects of planning method.
MATERIALS AND METHODS: In total, 337 participants with intermediate-risk disease and prospectively collected toxicity data were included. Patients were matched on prostate and rectum/bladder volumes and on radiotherapy dose for toxicity comparisons. The primary outcome was grade 2 or higher Radiation Therapy Oncology Group (RTOG) bowel or bladder toxicity at 2 years.
RESULTS: IP patients had smaller volumes of rectum irradiated to 50-70 Gy (P < 0.001); FP patients had smaller volumes of bladder irradiated to 74 Gy (P = 0.001). Acute grade 2 + bowel toxicity was worse with FP (27/53 [52%]; 11/53 [21%] IP; P = 0.0002); with no significant differences in acute urinary toxicity. At 2 years, RTOG grade 2 + bowel toxicity rates were FP 0/53 and IP 2/53 and RTOG grade 2 + bladder rates were FP 0/54 and IP 1/57.
CONCLUSIONS: Significant differences were found between dose-volume histograms from FP and IP methods. IP may result in small reductions in acute bowel toxicity but both techniques were associated with low rates of late radiotherapy side-effects.
Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
KEYWORDS: DVH; forward planning; intensity-modulated radiotherapy; inverse planning; prostate cancer; toxicity
Link to PubMed record
Author: O.F. Naismith, C. Griffin, I. Syndikus, C. South, H. Mayles, P. Mayles, V. Khoo, C. Scrase, J. Graham, S. Hassan, E. Hall, D.P. Dearnaley,
Abstract: AIMS: The CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose-volume histogram and toxicity data were compared to explore the effects of planning method.
MATERIALS AND METHODS: In total, 337 participants with intermediate-risk disease and prospectively collected toxicity data were included. Patients were matched on prostate and rectum/bladder volumes and on radiotherapy dose for toxicity comparisons. The primary outcome was grade 2 or higher Radiation Therapy Oncology Group (RTOG) bowel or bladder toxicity at 2 years.
RESULTS: IP patients had smaller volumes of rectum irradiated to 50-70 Gy (P < 0.001); FP patients had smaller volumes of bladder irradiated to 74 Gy (P = 0.001). Acute grade 2 + bowel toxicity was worse with FP (27/53 [52%]; 11/53 [21%] IP; P = 0.0002); with no significant differences in acute urinary toxicity. At 2 years, RTOG grade 2 + bowel toxicity rates were FP 0/53 and IP 2/53 and RTOG grade 2 + bladder rates were FP 0/54 and IP 1/57.
CONCLUSIONS: Significant differences were found between dose-volume histograms from FP and IP methods. IP may result in small reductions in acute bowel toxicity but both techniques were associated with low rates of late radiotherapy side-effects.
Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
KEYWORDS: DVH; forward planning; intensity-modulated radiotherapy; inverse planning; prostate cancer; toxicity
Link to PubMed record
Monday 12 August 2019
WUTH publication: Respiratory polymerase chain reaction - point of care test for patients with suspected influenza on the ambulatory care unit
Citation: Future Healthcare Journal. 2019, 6(Sup 1), 107
Author: Jayachandran A, Ahmad M
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Author: Jayachandran A, Ahmad M
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WUTH publication: Malnutrition, nutritional interventions and clinical outcomes of patients with acute small bowel obstruction: results from a national, multicentre, prospective audit
Citation: BMJ Open. 2019, 9(7), e029235
Author: Lee MJ, Sayers AE, Drake TM, Singh P, Bradburn M, Wilson TR, Murugananthan A, Walsh CJ, Fearnhead NS, NASBO Steering Group and NASBO Collaborators
Abstract: OBJECTIVE: The aim of this study was to assess the nutritional status of patients presenting with small bowel obstruction (SBO), along with associated nutritional interventions and clinical outcomes.
DESIGN: Prospective cohort study.
SETTING: 131 UK hospitals with acute surgical services.
PARTICIPANTS: 2069 adult patients with a diagnosis of SBO were included in this study. The mean age was 67.0 years and 54.7% were female.
PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was in-hospital mortality. Secondary outcomes recorded included: major complications (composite of in-hospital mortality, reoperation, unplanned intensive care admission and 30-day readmission), complications arising from surgery (anastomotic leak, wound dehiscence), infection (pneumonia, surgical site infection, intra-abdominal infection, urinary tract infection, venous catheter infection), cardiac complications, venous thromboembolism and delirium.
RESULTS: Postoperative adhesions were the most common cause of SBO (49.1%). Early surgery (<24 hours postadmission) took place in 30.0% of patients, 22.0% underwent delayed operation and 47.9% were managed non-operatively. Malnutrition as stratified by Nutritional Risk Index was common, with 35.7% at moderate risk and 5.7% at severe risk of malnutrition. Dietitian review occurred in just 36.4% and 55.9% of the moderate and severe risk groups. In the low risk group, 30.3% received nutritional intervention compared with 40.7% in moderate risk group and 62.7% in severe risk group. In comparison to the low risk group, patients who were at severe or moderate risk of malnutrition had 4.2 and 2.4 times higher unadjusted risk of in-hospital mortality, respectively. Propensity-matched analysis found no difference in outcomes based on use or timing of parenteral nutrition.
CONCLUSIONS: Malnutrition on admission is associated with worse outcomes in patients with SBO, and marked variation in management of malnutrition was observed. Future trials should focus on identifying effective and cost-effective nutritional interventions in SBO.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: adult surgery; nutritional support; perioperative care
Link to PubMed record
Author: Lee MJ, Sayers AE, Drake TM, Singh P, Bradburn M, Wilson TR, Murugananthan A, Walsh CJ, Fearnhead NS, NASBO Steering Group and NASBO Collaborators
Abstract: OBJECTIVE: The aim of this study was to assess the nutritional status of patients presenting with small bowel obstruction (SBO), along with associated nutritional interventions and clinical outcomes.
DESIGN: Prospective cohort study.
SETTING: 131 UK hospitals with acute surgical services.
PARTICIPANTS: 2069 adult patients with a diagnosis of SBO were included in this study. The mean age was 67.0 years and 54.7% were female.
PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was in-hospital mortality. Secondary outcomes recorded included: major complications (composite of in-hospital mortality, reoperation, unplanned intensive care admission and 30-day readmission), complications arising from surgery (anastomotic leak, wound dehiscence), infection (pneumonia, surgical site infection, intra-abdominal infection, urinary tract infection, venous catheter infection), cardiac complications, venous thromboembolism and delirium.
RESULTS: Postoperative adhesions were the most common cause of SBO (49.1%). Early surgery (<24 hours postadmission) took place in 30.0% of patients, 22.0% underwent delayed operation and 47.9% were managed non-operatively. Malnutrition as stratified by Nutritional Risk Index was common, with 35.7% at moderate risk and 5.7% at severe risk of malnutrition. Dietitian review occurred in just 36.4% and 55.9% of the moderate and severe risk groups. In the low risk group, 30.3% received nutritional intervention compared with 40.7% in moderate risk group and 62.7% in severe risk group. In comparison to the low risk group, patients who were at severe or moderate risk of malnutrition had 4.2 and 2.4 times higher unadjusted risk of in-hospital mortality, respectively. Propensity-matched analysis found no difference in outcomes based on use or timing of parenteral nutrition.
CONCLUSIONS: Malnutrition on admission is associated with worse outcomes in patients with SBO, and marked variation in management of malnutrition was observed. Future trials should focus on identifying effective and cost-effective nutritional interventions in SBO.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: adult surgery; nutritional support; perioperative care
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WUTH publication: With a national restructuring of physician training to include critical care, what is the educational value of intensive care for physician trainees?
Citation: Clinical Medicine. 2019, 19(Sup 3), 37-8
Authors: Paes M, Williams T
Link to PubMed record
Authors: Paes M, Williams T
Link to PubMed record
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