Citation: Cancers. 2020, 12(6), E1490
Author: Eirini Terpsi Vitti, Andrzej Kacperek, Jason L Parsons
Abstract: The response of head and neck squamous cell carcinoma (HNSCC) to radiotherapy depends on human papillomavirus type 16 (HPV) status, and where improved outcome and survival is observed in HPV-positive disease. However, strategies to further radiosensitise the tumours, particularly relatively radioresistant HPV-negative HNSCC, are actively being sought. The impact of targeting the major protein kinases involved in the signaling of DNA double-strand break (DSB) repair, namely ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and Rad3-related (ATR), and the catalytic subunit of DNA-dependent protein kinase (DNA-Pkcs), on the radiosensitisation of HNSCC cells was examined. The response to both conventional photon radiotherapy, but also proton beam therapy, was analysed by clonogenic assays and 3D spheroid growth. We observed that inhibition of ATM, ATR, and particularly DNA-Pkcs, caused a significant reduction in HNSCC cell survival post-irradiation with both photons and protons, with less of an impact on the most radiosensitive HPV-positive cell line. The inhibition of DNA-Pkcs and, to a lesser extent ATM, in combination with radiation was also more effective at inhibiting the growth of 3D spheroids derived from relatively radioresistant HPV-negative HNSCC. Similar effects of the inhibitors were observed comparing photon and proton irradiation, demonstrating the potential for targeting DSB repair as an effective combination treatment for HNSCC.
Keywords: ATM; ATR; DNA repair; DNA-PKcs; ionising radiation; proton beam therapy.
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Thursday 25 June 2020
CCC publication: NUC-1031, Use of ProTide Technology to Circumvent Gemcitabine Resistance: Current Status in Clinical Trials
Citation: Medical Oncology. 2020, 37(7), 1-10
Author: Zainul Abedin Kapacee, Jennifer J Knox, Daniel Palmer, Sarah P Blagden, Angela Lamarca, Juan W Valle, Mairéad G McNamara
Abstract: Background: Resistance to gemcitabine chemotherapy is common in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC) and ovarian cancers (OC), conferring poor survival. Use of ProTide technology led to the development of a 'partially-activated' monophosphorylated gemcitabine compound, termed NUC-1031. NUC-1031 enters cancer cells independent of the human equilibrative nucleoside transporter, does not require deoxycytidine kinase-mediated activation and resists cytidine deaminase-mediated breakdown into toxic by-products.
Current findings: The phase I PRO-001 trial recruited 68 patients with advanced solid tumours; of the 49 patients that had response-evaluable disease, 5 (10%) had a partial response (PR) and 33 (67%) had stable disease (SD). Subsequently, the PRO-002 study assessed the safety and efficacy of NUC-1031 combined with carboplatin for patients with OC (n = 25); preliminary data from this study reported one (4%) unconfirmed complete response (CR), 8 (35%) PRs and 13 (57%) patients with SD, the final outcome data are awaited. The ABC-08 trial for advanced BTC assessed safety and efficacy of NUC-1031 combined with cisplatin; 14 patients were recruited with a 50% objective response rate in the intention to treat population at interim analysis. ACELARATE, the phase III trial in first-line advanced PDAC comparing NUC-1031 to gemcitabine monotherapy, recruited 200 patients but has been paused for futility analysis.
Conclusion: Early studies demonstrate NUC-1031 is well tolerated with favourable pharmacokinetic profiles. NUC-1031 use in PDAC remains unclear, but encouraging results of disease control in BTC and OC has prompted phase II and III trial development. NuTide 121, is a phase III trial comparing cisplatin-NUC 1031 combination to the standard of care cisplatin-gemcitabine and recruitment is ongoing. Recruiting trials and mature data from existing studies will help inform on the impact of NUC-1031 on patient survival over standard gemcitabine.
Keywords: Acelarin; Biliary tract cancer; Gemcitabine resistance; NUC-1031; Ovarian cancer; Pancreatic ductal adenocarcinoma; Phase I trial.
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Author: Zainul Abedin Kapacee, Jennifer J Knox, Daniel Palmer, Sarah P Blagden, Angela Lamarca, Juan W Valle, Mairéad G McNamara
Abstract: Background: Resistance to gemcitabine chemotherapy is common in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC) and ovarian cancers (OC), conferring poor survival. Use of ProTide technology led to the development of a 'partially-activated' monophosphorylated gemcitabine compound, termed NUC-1031. NUC-1031 enters cancer cells independent of the human equilibrative nucleoside transporter, does not require deoxycytidine kinase-mediated activation and resists cytidine deaminase-mediated breakdown into toxic by-products.
Current findings: The phase I PRO-001 trial recruited 68 patients with advanced solid tumours; of the 49 patients that had response-evaluable disease, 5 (10%) had a partial response (PR) and 33 (67%) had stable disease (SD). Subsequently, the PRO-002 study assessed the safety and efficacy of NUC-1031 combined with carboplatin for patients with OC (n = 25); preliminary data from this study reported one (4%) unconfirmed complete response (CR), 8 (35%) PRs and 13 (57%) patients with SD, the final outcome data are awaited. The ABC-08 trial for advanced BTC assessed safety and efficacy of NUC-1031 combined with cisplatin; 14 patients were recruited with a 50% objective response rate in the intention to treat population at interim analysis. ACELARATE, the phase III trial in first-line advanced PDAC comparing NUC-1031 to gemcitabine monotherapy, recruited 200 patients but has been paused for futility analysis.
Conclusion: Early studies demonstrate NUC-1031 is well tolerated with favourable pharmacokinetic profiles. NUC-1031 use in PDAC remains unclear, but encouraging results of disease control in BTC and OC has prompted phase II and III trial development. NuTide 121, is a phase III trial comparing cisplatin-NUC 1031 combination to the standard of care cisplatin-gemcitabine and recruitment is ongoing. Recruiting trials and mature data from existing studies will help inform on the impact of NUC-1031 on patient survival over standard gemcitabine.
Keywords: Acelarin; Biliary tract cancer; Gemcitabine resistance; NUC-1031; Ovarian cancer; Pancreatic ductal adenocarcinoma; Phase I trial.
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CCC publication: Immune Checkpoint Blockade: Releasing the Breaks or a Protective Barrier to COVID-19 Severe Acute Respiratory Syndrome?
Citation: British Journal of Cancer. 2020, 123(5), 691-3. Online ahead of print
Author: Oliver J Pickles, Lennard Y W Lee, Thomas Starkey, Luke Freeman-Mills, Anna Olsson-Brown, Vinton Cheng, Daniel J Hughes, Alvin Lee, Karin Purshouse, Gary Middleton
Abstract: The rapid emergence of COVID-19 has sent shockwaves through healthcare systems globally, with cancer patients at increased risk. The interplay of the virus and host immune system has been implicated in the development of ARDS. Immunotherapy agents have the potential to adversely potentiate this phenomenon, requiring careful real-world observation.
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Author: Oliver J Pickles, Lennard Y W Lee, Thomas Starkey, Luke Freeman-Mills, Anna Olsson-Brown, Vinton Cheng, Daniel J Hughes, Alvin Lee, Karin Purshouse, Gary Middleton
Abstract: The rapid emergence of COVID-19 has sent shockwaves through healthcare systems globally, with cancer patients at increased risk. The interplay of the virus and host immune system has been implicated in the development of ARDS. Immunotherapy agents have the potential to adversely potentiate this phenomenon, requiring careful real-world observation.
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CCC publication: Older Cancer Patients During the COVID-19 Epidemic: Practice Proposal of the International Geriatric Radiotherapy Group
Citation: Cancers. 2020, 12(5), 1287
Author: Nam P Nguyen, Vincent Vinh-Hung, Brigitta Baumert, Alice Zamagni, Meritxell Arenas, Micaela Motta, Pedro Carlos Lara, Arthur Sun Myint, Marta Bonet, Tiberiu Popescu, Te Vuong, Gokula Kumar Appalanaido, Lurdes Trigo, Ulf Karlsson, Juliette Thariat
Abstract: The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.
Keywords: cancer patients; corona virus 19; epidemic; older; treatment.
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Author: Nam P Nguyen, Vincent Vinh-Hung, Brigitta Baumert, Alice Zamagni, Meritxell Arenas, Micaela Motta, Pedro Carlos Lara, Arthur Sun Myint, Marta Bonet, Tiberiu Popescu, Te Vuong, Gokula Kumar Appalanaido, Lurdes Trigo, Ulf Karlsson, Juliette Thariat
Abstract: The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.
Keywords: cancer patients; corona virus 19; epidemic; older; treatment.
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CCC publication: Inhibition of ATM Increases the Radiosensitivity of Uveal Melanoma Cells to Photons and Protons
Citation: Cancers. 2020, 12(6), E1388.
Author: Rumana N Hussain, Sarah E Coupland, Jakub Khzouz, Helen Kalirai, Jason L Parsons
Abstract: Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%-95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We observed a broad range of radiosensitivity of different UM cell lines to X-rays and protons, with increased radioresistance correlating with elevated protein expression of ataxia telangiectasia mutated (ATM), a protein kinase involved in the signaling and repair of DNA double strand breaks. The use of an ATM inhibitor in UM cell lines enhanced radiosensitivity following both X-ray and proton irradiation, particularly in cells that contained high levels of ATM protein which are otherwise comparatively radioresistant. In proton-irradiated compared with non-irradiated primary enucleated UM patient samples, there was no significant difference in ATM protein expression. Our study therefore suggests that ATM is a potential target for increasing the radiosensitivity of more resistant UM subgroups.
Keywords: ATM; DNA damage; DNA repair; ionizing radiation; protons; uveal melanoma.
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Author: Rumana N Hussain, Sarah E Coupland, Jakub Khzouz, Helen Kalirai, Jason L Parsons
Abstract: Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%-95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We observed a broad range of radiosensitivity of different UM cell lines to X-rays and protons, with increased radioresistance correlating with elevated protein expression of ataxia telangiectasia mutated (ATM), a protein kinase involved in the signaling and repair of DNA double strand breaks. The use of an ATM inhibitor in UM cell lines enhanced radiosensitivity following both X-ray and proton irradiation, particularly in cells that contained high levels of ATM protein which are otherwise comparatively radioresistant. In proton-irradiated compared with non-irradiated primary enucleated UM patient samples, there was no significant difference in ATM protein expression. Our study therefore suggests that ATM is a potential target for increasing the radiosensitivity of more resistant UM subgroups.
Keywords: ATM; DNA damage; DNA repair; ionizing radiation; protons; uveal melanoma.
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CCC publication: Monte-Carlo-computed Dose, Kerma and Fluence Distributions in Heterogeneous Slab Geometries Irradiated by Small Megavoltage Photon Fields
Citation: Physics in medicine and biology. 2020 June. Online ahead of print
Author: Sudhir Kumar, Alan E Nahum, Indrin J Chetty
Abstract: Small-field dosimetry is central to the planning and delivery of radiotherapy to patients with cancer. Small-field dosimetry is beset by complex issues, such as loss of charged-particle equilibrium (CPE), source occlusion and electron scattering effects in low-density tissues. The purpose of the present research was to elucidate the fundamental physics of small fields through the computation of absorbed dose, kerma and fluence distributions in heterogeneous media using the Monte-Carlo method. Absorbed dose and kerma were computed using the DOSRZnrc Monte-Carlo (MC) user-code for beams with square field sizes ranging from 0.25 × 0.25 to 7× 7 cm2 (for 6 MV 'full linac' geometry) and 0.25 × 0.25 to 16 × 16 cm2 (for 15 MV 'full linac' geometry). In the bone inhomogeneity the dose increases (vs. homogeneous water) for field sizes < 1 × 1 cm2 at 6 MV and ≤ 3 × 3 cm2 at 15 MV and decreases (vs. homogeneous water) for field sizes ≥ 3 × 3 cm2 at 6 MV and ≥ 5 × 5 cm2 at 15 MV. In the lung inhomogeneity there is negligible decrease in dose compared to in uniform water for field sizes > 5 × 5 cm2 at 6 MV and ≥ 16 × 16 cm2 at 15 MV, consistent with the Fano theorem. The near-unity value of the absorbed-dose to collision-kerma ratio, D/Kcol, at the centre of the bone and lung slabs in the heterogeneous phantom demonstrated that CPE is achieved in bone for field sizes > 1 × 1 cm2 at 6 MV and > 5 × 5 cm2 at 15 MV; CPE is achieved in lung at field sizes > 5 × 5 cm2 at 6 MV and ≥ 16 × 16 cm2 at 15 MV. Electron-fluence perturbation factors for the 0.25 × 0.25 cm2 field were 1.231 and 1.403 for bone-to-water and 0.454 and 0.333 for lung-to-water were at 6 and 15 MV respectively. For field sizes large enough for quasi-CPE, the MC-derived dose-perturbation factors, lung-to-water, were close to unity; electron-fluence perturbation factors, lung-to-water, were ~1.0, consistent with the 'Fano' theorem. At 15 MV in the lung inhomogeneity the magnitude and also the 'shape' of the primary electron-fluence spectrum differed significantly from that in water. Beam penumbrae relative to water were narrower in the bone inhomogeneity and broader in the lung inhomogeneity for all field sizes.
Keywords: Fano theorem; Monte Carlo; absorbed dose; electron-fluence perturbation; kerma; non-equilibrium photon fields.
Link to PubMed record
Author: Sudhir Kumar, Alan E Nahum, Indrin J Chetty
Abstract: Small-field dosimetry is central to the planning and delivery of radiotherapy to patients with cancer. Small-field dosimetry is beset by complex issues, such as loss of charged-particle equilibrium (CPE), source occlusion and electron scattering effects in low-density tissues. The purpose of the present research was to elucidate the fundamental physics of small fields through the computation of absorbed dose, kerma and fluence distributions in heterogeneous media using the Monte-Carlo method. Absorbed dose and kerma were computed using the DOSRZnrc Monte-Carlo (MC) user-code for beams with square field sizes ranging from 0.25 × 0.25 to 7× 7 cm2 (for 6 MV 'full linac' geometry) and 0.25 × 0.25 to 16 × 16 cm2 (for 15 MV 'full linac' geometry). In the bone inhomogeneity the dose increases (vs. homogeneous water) for field sizes < 1 × 1 cm2 at 6 MV and ≤ 3 × 3 cm2 at 15 MV and decreases (vs. homogeneous water) for field sizes ≥ 3 × 3 cm2 at 6 MV and ≥ 5 × 5 cm2 at 15 MV. In the lung inhomogeneity there is negligible decrease in dose compared to in uniform water for field sizes > 5 × 5 cm2 at 6 MV and ≥ 16 × 16 cm2 at 15 MV, consistent with the Fano theorem. The near-unity value of the absorbed-dose to collision-kerma ratio, D/Kcol, at the centre of the bone and lung slabs in the heterogeneous phantom demonstrated that CPE is achieved in bone for field sizes > 1 × 1 cm2 at 6 MV and > 5 × 5 cm2 at 15 MV; CPE is achieved in lung at field sizes > 5 × 5 cm2 at 6 MV and ≥ 16 × 16 cm2 at 15 MV. Electron-fluence perturbation factors for the 0.25 × 0.25 cm2 field were 1.231 and 1.403 for bone-to-water and 0.454 and 0.333 for lung-to-water were at 6 and 15 MV respectively. For field sizes large enough for quasi-CPE, the MC-derived dose-perturbation factors, lung-to-water, were close to unity; electron-fluence perturbation factors, lung-to-water, were ~1.0, consistent with the 'Fano' theorem. At 15 MV in the lung inhomogeneity the magnitude and also the 'shape' of the primary electron-fluence spectrum differed significantly from that in water. Beam penumbrae relative to water were narrower in the bone inhomogeneity and broader in the lung inhomogeneity for all field sizes.
Keywords: Fano theorem; Monte Carlo; absorbed dose; electron-fluence perturbation; kerma; non-equilibrium photon fields.
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CCC publication: An Unexpected Cause of Iron Deficiency
Citation: Gut. 2020, gutjnl-2020-321830. Online ahead of print.
Author: Thomas Edward Conley, Timothy Andrews, Arvind Arumainathan, Paul O'Toole, Philip J Smith, Sreedhar Subramanian
Abstract: Keywords: endoscopy; gastrointestinal lymphoma; iron deficiency; mucosa associated lymphoid tissue.
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Author: Thomas Edward Conley, Timothy Andrews, Arvind Arumainathan, Paul O'Toole, Philip J Smith, Sreedhar Subramanian
Abstract: Keywords: endoscopy; gastrointestinal lymphoma; iron deficiency; mucosa associated lymphoid tissue.
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CCC publication: Radiotherapy for COVID-19: Primum Non Nocere
Citation: Radiotherapy and Oncology. 2020, 149, 236-37. Online ahead of print.
Author: Ian S. Boon, Tracy P.T. Au Yong, Cheng S. Boon,
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Author: Ian S. Boon, Tracy P.T. Au Yong, Cheng S. Boon,
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CCC publication: NOTCH: The National Oncology Trainees Collaborative for Healthcare Research
Citation: Clinical Oncology. 2020, 32(10), 632-5. Online ahead of print
Author: C M Jones, A Olsson-Brown, C Dobeson, Trainee Board of the National Oncology Trainees Collaborative for Healthcare Research
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Author: C M Jones, A Olsson-Brown, C Dobeson, Trainee Board of the National Oncology Trainees Collaborative for Healthcare Research
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CCC pubilcation: Coronavirus Disease 2019: the Pivotal Role of UK Clinical Oncology and the UK Coronavirus
Citation: Clinical Oncology. 2021, 33(1). Publication Date Jan 2021
Author: J. Best, T. Starkey, A. Chatterjee, D. Fackrell, L. Pettit, N. Srihari, H. Tween, A. Olsson-Brown, V. Cheng, D.J. Hughes, A.J.X. Lee, K. Purshouse, R. Arnold, UK Coronavirus Cancer Monitoring Project Team, S. Sivakumar, J.-B. Cazier, L.Y.W. Lee,
Author: J. Best, T. Starkey, A. Chatterjee, D. Fackrell, L. Pettit, N. Srihari, H. Tween, A. Olsson-Brown, V. Cheng, D.J. Hughes, A.J.X. Lee, K. Purshouse, R. Arnold, UK Coronavirus Cancer Monitoring Project Team, S. Sivakumar, J.-B. Cazier, L.Y.W. Lee,
CCC publication: Management of the Axilla Following Neoadjuvant Chemotherapy for Breast Cancer- A Change in Practice
Citation: The Surgeon. 2020, S1479-666X(20), 30020-2. Online ahead of print
Author: Bahaty Riogi, Raj Sripadam, David Barker, Olga Harris, Helen Innes, Leena Chagla
Abstract: Objectives: Chemotherapy in the neo adjuvant setting has allowed downsizing of breast tumours thus allowing patients to benefit from breast conservation surgery. The effect of neoadjuvant chemotherapy (NAC) has also been observed in the axilla but most units are still treating the axilla with axillary lymph node dissection (ALND).
Materials and methods: A prospective database of breast cancer patients receiving NAC between 2007 and 2016 at a single breast unit was reviewed. The management of the axilla and outcomes was studied.
Results: 165 patients received NAC, 123 (74.5%) were clinically/radiologically node positive and 42 were negative. Median age was 50 years. 26.7% had triple negative disease and 34.5% were HER2 positive. 56/123 (45.5%) patients with positive nodes at the outset responded completely to NAC. 40 patients with positive nodes pre-NAC had post NAC SLNB with 37 requiring adjuvant radiotherapy only. 83/123 went directly to ALND post NAC and of these 27 were node negative and therefore may be considered to have had an unnecessary ALND. Overall mortality was 20.6% (34), local recurrence in the breast or mastectomy scar was 3.6% (6) but there was no recurrence in the axilla (0/165) with a median follow up of 67 months.
Conclusion: There is no clear evidence for management of the axilla post NAC. We have used best available evidence to change our practice over the years and our results should encourage others to de-escalate treatment of the axilla in line with the recently published multidisciplinary guidance on axillary surgery following neoadjuvant chemotherapy.
Keywords: Axilla management; Breast cancer; Neoadjuvant chemotherapy.
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Author: Bahaty Riogi, Raj Sripadam, David Barker, Olga Harris, Helen Innes, Leena Chagla
Abstract: Objectives: Chemotherapy in the neo adjuvant setting has allowed downsizing of breast tumours thus allowing patients to benefit from breast conservation surgery. The effect of neoadjuvant chemotherapy (NAC) has also been observed in the axilla but most units are still treating the axilla with axillary lymph node dissection (ALND).
Materials and methods: A prospective database of breast cancer patients receiving NAC between 2007 and 2016 at a single breast unit was reviewed. The management of the axilla and outcomes was studied.
Results: 165 patients received NAC, 123 (74.5%) were clinically/radiologically node positive and 42 were negative. Median age was 50 years. 26.7% had triple negative disease and 34.5% were HER2 positive. 56/123 (45.5%) patients with positive nodes at the outset responded completely to NAC. 40 patients with positive nodes pre-NAC had post NAC SLNB with 37 requiring adjuvant radiotherapy only. 83/123 went directly to ALND post NAC and of these 27 were node negative and therefore may be considered to have had an unnecessary ALND. Overall mortality was 20.6% (34), local recurrence in the breast or mastectomy scar was 3.6% (6) but there was no recurrence in the axilla (0/165) with a median follow up of 67 months.
Conclusion: There is no clear evidence for management of the axilla post NAC. We have used best available evidence to change our practice over the years and our results should encourage others to de-escalate treatment of the axilla in line with the recently published multidisciplinary guidance on axillary surgery following neoadjuvant chemotherapy.
Keywords: Axilla management; Breast cancer; Neoadjuvant chemotherapy.
Link to PubMed record
CCC publication: Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
Citation: The Lancet. Oncology. 2020, 21(7), 978-88
Author: Gilles Salles, Johannes Duell, Eva González Barca, Olivier Tournilhac, Wojciech Jurczak, Anna Marina Liberati, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Marc André, Nagesh Kalakonda, Martin Dreyling, Johannes Weirather, Maren Dirnberger-Hertweck, Sumeet Ambarkhane, Günter Fingerle-Rowson, Kami Maddocks,
Author: Gilles Salles, Johannes Duell, Eva González Barca, Olivier Tournilhac, Wojciech Jurczak, Anna Marina Liberati, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Marc André, Nagesh Kalakonda, Martin Dreyling, Johannes Weirather, Maren Dirnberger-Hertweck, Sumeet Ambarkhane, Günter Fingerle-Rowson, Kami Maddocks,
CCC publication: Looking a Gift Horse in the Mouth: Observations on NHS England's Interim Guidance on Pembrolizumab in Head and Neck Squamous Cell Cancer
Citation: Clinical Oncology. 2020, 32(8), 490–92. Online ahead of print
Author: K J Harrington, S A Bhide, M D Forster, J S Good, L Gunn, A Kong, A A Melcher, R Metcalf, P Nenclares, K L Newbold, C M Nutting, R Prestwich, J J Sacco, H Soliman, K H Wong
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WUTH publication: Training in Oral and Maxillofacial Surgery: A Medicine-First Perspective
Citation: The British Journal of Oral and Maxillofacial Surgery. 2020, 58(10), 1333-34. Epub 2020 Jun 20
Author: Rapaport BHJ, Gill K, Douglas J, Ali T, Brown JS
Abstract: Specialist registration in oral and maxillofacial surgery (OMFS) requires dual medical and dental qualification involving at least eight years of undergraduate study. Training has continued to evolve since dual qualification was introduced and has often resulted in unwarranted repetition. If a time-based curriculum is necessary, second degree trainees should be allowed to pursue research and audit, and gain relevant clinical experience in lieu of repeating previously covered material. Junior surgical training could be integrated into the second degree. A programme that records competencies during the second degree may demonstrate equivalent to other aspects of junior training. One barrier is timetabling, which often restricts the integration of second degree trainees with OMFS units. Junior training in OMFS could be streamlined if the content was agreed nationally. This would also offer the opportunity for those key institutions that implement these changes to take on a prominent role in OMFS training.
Keywords: Dental School; Medical School; Surgical; Training.
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Author: Rapaport BHJ, Gill K, Douglas J, Ali T, Brown JS
Abstract: Specialist registration in oral and maxillofacial surgery (OMFS) requires dual medical and dental qualification involving at least eight years of undergraduate study. Training has continued to evolve since dual qualification was introduced and has often resulted in unwarranted repetition. If a time-based curriculum is necessary, second degree trainees should be allowed to pursue research and audit, and gain relevant clinical experience in lieu of repeating previously covered material. Junior surgical training could be integrated into the second degree. A programme that records competencies during the second degree may demonstrate equivalent to other aspects of junior training. One barrier is timetabling, which often restricts the integration of second degree trainees with OMFS units. Junior training in OMFS could be streamlined if the content was agreed nationally. This would also offer the opportunity for those key institutions that implement these changes to take on a prominent role in OMFS training.
Keywords: Dental School; Medical School; Surgical; Training.
Link to PubMed record
Monday 15 June 2020
WUTH publication: Vision Screening Assessment (VISA) Tool: Diagnostic Accuracy Validation of a Novel Screening Tool in Detecting Visual Impairment Among Stroke Survivors
Citation: BMJ Open. 2020, 10(6), e033639
Author: Rowe FJ, Hepworth L, Howard C, Bruce A, Smerdon V, Payne T, Jimmieson P, Burnside G
Abstract: Purpose: Screening for visual problems in stroke survivors is not standardised. Visual problems that remain undetected or poorly identified can create unmet needs for stroke survivors. We report the validation of a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors.
Methods: We conducted a prospective case cohort comparative study in four centres to validate the VISA tool against a specialist reference vision assessment. VISA is available in print or as an app (Medicines and Healthcare products Regulatory Agency regulatory approved); these were used equally for two groups. Both VISA and the comprehensive reference vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention. The primary outcome measure was the presence or absence of visual impairment.
Results: Two hundred and twenty-one stroke survivors were screened. Specialist reference vision assessment was by experienced orthoptists. Full completion of screening and reference vision assessment was achieved for 201 stroke survivors. VISA print was completed for 101 stroke survivors; VISA app was completed for 100. Sensitivity and specificity of VISA print was 97.67% and 66.67%, respectively. Overall agreement was substantial; K=0.648. Sensitivity and specificity of VISA app was 88.31% and 86.96%, respectively. Overall agreement was substantial; K=0.690. Lowest agreement was found for screening of eye movement and near visual acuity.
Conclusions: This validation study indicates acceptability of VISA for screening of potential visual impairment in stroke survivors. Sensitivity and specificity were high indicating the accuracy of this screening tool. VISA is available in print or as an app allowing versatile uptake across multiple stroke settings.
Keywords: VISA; detection; orthoptics; screening; stroke; visual impairment.
Link to PubMed record
Author: Rowe FJ, Hepworth L, Howard C, Bruce A, Smerdon V, Payne T, Jimmieson P, Burnside G
Abstract: Purpose: Screening for visual problems in stroke survivors is not standardised. Visual problems that remain undetected or poorly identified can create unmet needs for stroke survivors. We report the validation of a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors.
Methods: We conducted a prospective case cohort comparative study in four centres to validate the VISA tool against a specialist reference vision assessment. VISA is available in print or as an app (Medicines and Healthcare products Regulatory Agency regulatory approved); these were used equally for two groups. Both VISA and the comprehensive reference vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention. The primary outcome measure was the presence or absence of visual impairment.
Results: Two hundred and twenty-one stroke survivors were screened. Specialist reference vision assessment was by experienced orthoptists. Full completion of screening and reference vision assessment was achieved for 201 stroke survivors. VISA print was completed for 101 stroke survivors; VISA app was completed for 100. Sensitivity and specificity of VISA print was 97.67% and 66.67%, respectively. Overall agreement was substantial; K=0.648. Sensitivity and specificity of VISA app was 88.31% and 86.96%, respectively. Overall agreement was substantial; K=0.690. Lowest agreement was found for screening of eye movement and near visual acuity.
Conclusions: This validation study indicates acceptability of VISA for screening of potential visual impairment in stroke survivors. Sensitivity and specificity were high indicating the accuracy of this screening tool. VISA is available in print or as an app allowing versatile uptake across multiple stroke settings.
Keywords: VISA; detection; orthoptics; screening; stroke; visual impairment.
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Tuesday 9 June 2020
WUTH publication: Radiotherapy for COVID-19: Primum Non Nocere
Citation: Radiotherapy and Oncology. 2020, S0167-8140(20), 30302-9
Author: Boon IS, Yong TPTA, Boon CS
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Author: Boon IS, Yong TPTA, Boon CS
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WUTH publication: Clozapine Rechallenge and Initiation Despite Neutropenia- A Practical, Step-By-Step Guide
Citation: BMC psychiatry. 2020, 20(1), 279
Author: Silva E, Higgins M, Hammer B, Stephenson P
Abstract: Clozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.
Keywords: *Neutrophils.; Agranulocytosis/drug therapy*; Antipsychotic Agents/administration & dosage/*adverse effects.; Clozapine.; Clozapine/*adverse effects.; Forensic mental health services.; Granulocyte-Colony-Stimulating Factor/*therapeutic use.; Lithium/*therapeutic use.; Neutropenia/blood/chemically induced/ethnology/*therapy.; Schizophrenia/drug therapy*..
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Author: Silva E, Higgins M, Hammer B, Stephenson P
Abstract: Clozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.
Keywords: *Neutrophils.; Agranulocytosis/drug therapy*; Antipsychotic Agents/administration & dosage/*adverse effects.; Clozapine.; Clozapine/*adverse effects.; Forensic mental health services.; Granulocyte-Colony-Stimulating Factor/*therapeutic use.; Lithium/*therapeutic use.; Neutropenia/blood/chemically induced/ethnology/*therapy.; Schizophrenia/drug therapy*..
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WUTH publication: Special Communication: Evaluation and Treatment of Thoracic Outlet Syndrome During the Global Pandemic Due to SARS-CoV-2 and COVID-19
Citation: Journal of Vascular Surgery. 2020, 72(3), 790-8. Epub 2020 Jun 1
Author: Ohman JW, Annest SJ, Azizzadeh A, Burt BM, Caputo FJ, Chan C, Donahue DM, Freischlag JA, Gelabert HA, Humphries MD, Illig KA, Lee JT, Lum YW, Meyer RD, Pearl GJ, Ransom EF, Sanders RJ, Teijink JAW, Vaccaro PS, van Sambeek MRHM, Vemuri C, Thompson RW
Abstract: The global SARS-CoV-2/COVID-19 pandemic has required a reduction in non-emergency treatment for a variety of disorders. This report summarizes conclusions of an international multidisciplinary consensus group assembled to address evaluation and treatment of patients with thoracic outlet syndrome (TOS), a group of conditions characterized by extrinsic compression of the neurovascular structures serving the upper extremity. The following recommendations were developed in relation to the 3 defined types of TOS (neurogenic, venous, and arterial) and 3 phases of pandemic response (preparatory, urgent with limited resources, and emergency with complete diversion of resources): (1) In-person evaluation and treatment for neurogenic TOS (interventional or surgical) is generally postponed during all pandemic phases, with telephone/telemedicine visits and at-home physical therapy exercises recommended when feasible. (2) Venous TOS presenting with acute upper extremity deep vein thrombosis (Paget-Schroetter syndrome) is managed primarily with anticoagulation, with percutaneous interventions for venous TOS (thrombolysis) considered in early phases (I and II) and surgical treatment delayed until pandemic conditions resolve. Catheter-based interventions may also be considered for selected patients with central subclavian vein obstruction and threatened hemodialysis access in all pandemic phases, with definitive surgical treatment postponed. (3) Evaluation and surgical treatment for arterial TOS should be reserved for limb-threatening situations, such as acute upper extremity ischemia or acute digital embolization, in all phases of pandemic response. In late pandemic phases surgery should be restricted to thrombolysis or brachial artery thromboembolectomy, with more definitive treatment delayed until pandemic conditions resolve.
Keywords: axillary artery; brachial plexus; consensus; coronavirus; deep vein thrombosis; endovascular treatment; hospital resources; neurogenic; subclavian artery; subclavian vein; surgical treatment; teleconference; telemedicine; thromboembolism; triage; upper extremity.
Link to PubMed record
Author: Ohman JW, Annest SJ, Azizzadeh A, Burt BM, Caputo FJ, Chan C, Donahue DM, Freischlag JA, Gelabert HA, Humphries MD, Illig KA, Lee JT, Lum YW, Meyer RD, Pearl GJ, Ransom EF, Sanders RJ, Teijink JAW, Vaccaro PS, van Sambeek MRHM, Vemuri C, Thompson RW
Abstract: The global SARS-CoV-2/COVID-19 pandemic has required a reduction in non-emergency treatment for a variety of disorders. This report summarizes conclusions of an international multidisciplinary consensus group assembled to address evaluation and treatment of patients with thoracic outlet syndrome (TOS), a group of conditions characterized by extrinsic compression of the neurovascular structures serving the upper extremity. The following recommendations were developed in relation to the 3 defined types of TOS (neurogenic, venous, and arterial) and 3 phases of pandemic response (preparatory, urgent with limited resources, and emergency with complete diversion of resources): (1) In-person evaluation and treatment for neurogenic TOS (interventional or surgical) is generally postponed during all pandemic phases, with telephone/telemedicine visits and at-home physical therapy exercises recommended when feasible. (2) Venous TOS presenting with acute upper extremity deep vein thrombosis (Paget-Schroetter syndrome) is managed primarily with anticoagulation, with percutaneous interventions for venous TOS (thrombolysis) considered in early phases (I and II) and surgical treatment delayed until pandemic conditions resolve. Catheter-based interventions may also be considered for selected patients with central subclavian vein obstruction and threatened hemodialysis access in all pandemic phases, with definitive surgical treatment postponed. (3) Evaluation and surgical treatment for arterial TOS should be reserved for limb-threatening situations, such as acute upper extremity ischemia or acute digital embolization, in all phases of pandemic response. In late pandemic phases surgery should be restricted to thrombolysis or brachial artery thromboembolectomy, with more definitive treatment delayed until pandemic conditions resolve.
Keywords: axillary artery; brachial plexus; consensus; coronavirus; deep vein thrombosis; endovascular treatment; hospital resources; neurogenic; subclavian artery; subclavian vein; surgical treatment; teleconference; telemedicine; thromboembolism; triage; upper extremity.
Link to PubMed record
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