Conventional Radiotherapy In Patients Research Articles

Randomized phase II selection trial of FLASH and conventional radiotherapy for patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma: A study protocol

BackgroundCutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most prevalent skin cancers in western countries. Surgery is the standard of care for these cancers and conventional external radiotherapy (CONV-RT) with conventional dose rate (0.03–0.06 Gy/sec) represents a good alternative when the patients or tumors are not amenable to surgery but routinely generates skin side effects. Low energy electron FLASH radiotherapy (FLASH-RT) is a new form of radiotherapy exploiting the biological advantage of the FLASH effect, which consists in delivering radiation dose in milliseconds instead of minutes in CONV-RT. In pre-clinical studies, when compared to CONV-RT, FLASH-RT induced a robust, reproducible and remarkable sparing of the normal healthy tissues, while the efficacy on tumors was preserved. In this context, we aim to prospectively evaluate FLASH-RT versus CONV-RT with regards to toxicity and oncological outcome in localized cutaneous BCC and SCC. MethodsThis is a randomized selection, non-comparative, phase II study of curative FLASH-RT versus CONV-RT in patients with T1-T2 N0 M0 cutaneous BCC and SCC. Patients will be randomly allocated to low energy electron FLASH-RT (dose rate: 220–270 Gy/s) or to CONV-RT arm. Small lesions (T1) will receive a single dose of 22 Gy and large lesions (T2) will receive 30 Gy in 5 fractions of 6 Gy over two weeks.The primary endpoint evaluates safety at 6 weeks after RT through grade ≥ 3 toxicity and efficacy through local control rate at 12 months. Approximately 60 patients in total will be randomized, considering on average 1–2 lesions and a maximum of 3 lesions per patients corresponding to the total of 96 lesions required. FLASH-RT will be performed using the Mobetron® (IntraOp, USA) with high dose rate functionality.LANCE (NCT05724875) is the first randomized trial evaluating FLASH-RT and CONV-RT in a curative setting.

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

During the COVID-19 pandemic, most scientific societies and health organizations proposed measures to protect the Health System and its professionals from mass utilization of its resources and getting infected by the virus, respectively. An unavoidable, yet not desirable, effect was the restriction of treatment of other diseases. As far as cancer treatment is concerned, national and international recommendations published in March 2020 1Simcock R. et al.COVID-19: global radiation oncology's targeted response for pandemic preparedness.Clin Transl Radiat Oncol. 2020; 22: 55-68https://doi.org/10.1016/j.ctro.2020.03.009Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 2Coles C.E. et al.International guidelines on radiation therapy for breast cancer during the COVID-19 pandemic.Clin Oncol. 2020; 32 (Elsevier LtdMay 01): 279-281https://doi.org/10.1016/j.clon.2020.03.006Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar, 3“Letter from Italy: first practical indications for radiation therapy departments during COVID-19 outbreak - ScienceDirect.” https://www.sciencedirect.com/science/article/pii/S0360301620309305 (accessed Apr. 27, 2020).Google Scholar, 4Cancer Research UK, “Coronavirus (COVID-19) and cancer treatment | Cancer Research UK,” March 2020. https://www.cancerresearchuk.org/about-cancer/cancer-in-general/coronavirus/cancer-treatment (accessed May 29, 2020).Google Scholar, 5European Society of Surgical Oncology (ESSO), “ESSO statement on COVID-19 :: ESSO,” March 2020. https://www.essoweb.org/news/esso-statement-covid-19/(accessed May 29, 2020).Google Scholar, 6French Hospital Federation, “COVID-19 et cancers solides : recommandations - Fédération Hospitalière de France (FHF),” Mar. 19, 2020. https://www.fhf.fr/Offre-de-soins-Qualite/Organisation-de-l-offre-de-soins/COVID-19-et-Cancers-Solides-Recommandations (accessed May 29, 2020).Google Scholar called for extra measures to be taken by the Surgical, Chemotherapy and Radiation Therapy (RT) professionals to protect themselves and patients alike from being infected by COVID-19. More specifically, concerning external RT, these measures proposed, among others:(i)Treatment omission for certain non-urgent cases and all COVID-19 positive patients,(ii)Prioritization for intent-to-cure treatments versus palliative ones,(iii)Prioritization of younger versus older patients (with 65 years old generally set as the cutoff age),(iv)Hypofractionation and Simultaneously Integrated Boost (SIB) – meaning less fractions, where possible, and(v)Reduction of the number of personnel present to As Low As Reasonably Achievable (ALARA). Generalized use of hypofractionated RT (hypoRT – point iv of the recommendations above) presents advantages for most health stakeholders, the most prominent being that it is cost-effective 7Yang J. et al.Cost-effectiveness of postmastectomy hypofractionated radiation therapy vs conventional fractionated radiation therapy for high-risk breast cancer.Breast. 2021; 58: 72-79https://doi.org/10.1016/j.breast.2021.04.002Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar8Zhou K. et al.Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: an ancillary study of the PROstate fractionated irradiation trial – PROFIT.Radiother. Oncol. 2022; 173: 306-312https://doi.org/10.1016/j.radonc.2022.06.014Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, and at an acceptable risk of more local irradiation-induced short-term irritations due to the higher dose per fraction. In this Commentary, we will highlight the quantitative advantages of hypoRT for payers and the qualitative (and, where measurable) quantitative advantages and disadvantages for patients, hospital managers and health professionals. Our results come from France but may easily be interpreted in absolute terms for other countries. In France, RT departments exist in the public and private sector. However, since cancer is considered a long-term condition, the Social Security System (SSS) reimburses all expenses, transportation and accommodation directly to the service provider, independently of them being private or public. This allows patients and their General Practitioners the liberty of choice, but, patients will more often than not go to the nearest RT department, independently of its status. This Commentary references the most recent data on cancer incidence for France 9G. Heuzé, M. Cariou, A. Billot-grasset, and E. Chatignoux, “Données d'incidences et de mortalité par cancers régionales et départementales, CORSE,” 2019. [Online]. Available: http://invs.santepubliquefrance.fr/content/download/153049/559098/version/3/file/rapport-estimations-regionales-departementales-incidence-mortalite-cancers-France-2007-2016-Corse.pdf.Google Scholar and optimal RT use 10Delaney G.P. Barton M.B. Evidence-based estimates of the demand for radiotherapy.Clin Oncol. 2015; 27: 70-76https://doi.org/10.1016/j.clon.2014.10.005Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar for the following 8 sites: Breast, Lung, Prostate, Rectum, Head and Neck, Pancreas, Brain (gliomas) and Bladder (Table 1). Based on Table 1, about 70% of cases would ideally require RT.Table 1Cancer incidence and optimal RT use in France for 8 sites.Cancer siteTotal number of cases 9G. Heuzé, M. Cariou, A. Billot-grasset, and E. Chatignoux, “Données d'incidences et de mortalité par cancers régionales et départementales, CORSE,” 2019. [Online]. Available: http://invs.santepubliquefrance.fr/content/download/153049/559098/version/3/file/rapport-estimations-regionales-departementales-incidence-mortalite-cancers-France-2007-2016-Corse.pdf.Google ScholarOptimal number of cases for RT 10Delaney G.P. Barton M.B. Evidence-based estimates of the demand for radiotherapy.Clin Oncol. 2015; 27: 70-76https://doi.org/10.1016/j.clon.2014.10.005Abstract Full Text Full Text PDF PubMed Scopus (91) Google ScholarBreast53,17246,260Lung39,63530,519Prostate51,02429,594Rectum11,0056,603Head and Neck14,20410,511Pancreas10,8595,321Brain (gliomas)4,9133,930Bladder11,6295,466 Open table in a new tab Number of fractions and dose per fraction for conventional RT (convRT), based on national French recommendations 11Mahé M.A. Barillot I. Chauvet B. Recommandations en radiothérapie externe et curiethérapie (Recorad) : 2e édition.Cancer/Radiotherapie. 2016; 20 (Elsevier Masson SASSep. 01): S4-S7https://doi.org/10.1016/j.canrad.2016.07.014Crossref Scopus (8) Google Scholar, and hypoRT, based on March 2020 informal consensus between 121 Radiation Oncologists 1Simcock R. et al.COVID-19: global radiation oncology's targeted response for pandemic preparedness.Clin Transl Radiat Oncol. 2020; 22: 55-68https://doi.org/10.1016/j.ctro.2020.03.009Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, are shown in Table 2.Table 2convRT and hypoRT number of fractions and dose per fraction.Cancer siteconvRT11Mahé M.A. Barillot I. Chauvet B. Recommandations en radiothérapie externe et curiethérapie (Recorad) : 2e édition.Cancer/Radiotherapie. 2016; 20 (Elsevier Masson SASSep. 01): S4-S7https://doi.org/10.1016/j.canrad.2016.07.014Crossref Scopus (8) Google ScholarhypoRT1Simcock R. et al.COVID-19: global radiation oncology's targeted response for pandemic preparedness.Clin Transl Radiat Oncol. 2020; 22: 55-68https://doi.org/10.1016/j.ctro.2020.03.009Abstract Full Text Full Text PDF PubMed Scopus (163) Google ScholarNumber of fractionsDose/fraction (Gy)Number of fractionsDose/fraction (Gy)Breast252152.67Lung332152.67Prostate382203Rectum25255Head and Neck352302Pancreas281.856.6Brain (gliomas)302152.67Bladder302202.75 Open table in a new tab Billing is straightforward in the public domain in France 12“Tarifs MCO et HAD | Publication ATIH.” https://www.atih.sante.fr/tarifs-mco-et-had (accessed Jun. 03, 2022).Google Scholar: there is a fixed preparatory cost (1063.27€ for 3D-CRT and 2367.73€ for IMRT/VMAT), along with a fixed cost per fraction (182.14€ for 3D-CRT and 408.17€ for IMRT/VMAT). In the private sector there is also a fixed preparatory cost, which does not depend on the RT technique used, set at 851€ for 2022.There is also a variable cost, which consists of two parts:•a fixed price per positioning image at 25.05€, with a maximum of 180 images per patient and 9 images per week, and•a variable price depending on a rather complicated equation dealing with the maximum dose per field, the size of each field, their number, the number of fractions and the energy used, but not the technique used 12“Tarifs MCO et HAD | Publication ATIH.” https://www.atih.sante.fr/tarifs-mco-et-had (accessed Jun. 03, 2022).Google Scholar. For the public domain, costs are calculated by adding the fixed cost to the product of the number of fractions and price per fraction. For the private sector, the average costs of all patients receiving convRT or hypoRT per cancer site for the years 2021 and 2022 in one French private center are referened here (using the 2022 price list). Table 3 presents the RT costs of convRT and hypoRT in France for the optimal number of cases in 2019 (Table 1), treated as per the Table 2 schemes. The Table presents the costs as if all patients would be treated at a public or at a private hospital.Table 3Theoretical difference in convRT and hypoRT costs for France for 8 cancer sites.Cancer siteconvRThypoRTPublic only (M€*M€ = one million euros.)Private only (M€*M€ = one million euros.)Public only (M€*M€ = one million euros.)Private only (M€*M€ = one million euros.)Breast259.83225.07175.57167.99Lung483.34366.23259.11211.42Prostate529.09473.50311.66341.53Rectum83.0152.8229.1124.03Head and Neck175.05126.13153.59109.37Pancreas73.4153.2123.4627.31Brain (gliomas)57.4335.3733.3720.61Bladder79.8743.7357.5636.89TOTAL:1,741.031,376.061,043.44939.15 M€ = one million euros. Open table in a new tab If all patients received their treatment at a public hospital, then global hypoRT use for these 8 cancer sites would result in a gain of 697.6 M€ per year. Meanwhile, if all patients were to be treated in the private sector, the relevant gain would be 436.9 M€. We do not know the ratio of patients that would use the public versus the private sector at any given period, but since RT is fully covered by the SSS in France, we can guess that half of the patients would prefer a public hospital, while the other half would go to a private clinic. Thus, on average, 567.2 M€ would be gained per year by the French SSS if these 8 cancer sites would be treated by hypoRT instead of convRT, meaning a gain of 36.4% of the total RT cost. This result can easily be generalized for other SSS and countries, since for these 8 cancer sites there would be 1,965,238 less fractions per year for a population of 67.25 million people 13“Bilan démographique 2019 - Insee Première - 1789.” https://www.insee.fr/fr/statistiques/4281618 (accessed Jun. 07, 2022).Google Scholar, so 29.2 thousand less fractions per million people per year. Additionally, these almost 2 million less fractions of RT automatically mean almost 2 million less patients travel from home to the RT department and back. This would result in a gain of about 121.8 M€ per year for the French SSS 14Dupin C. Vilotte F. Lagarde P. Petit A. Breton-Callu C. Évolution des pratiques médicales d'hypofractionnement en radiothérapie pour cancer du sein et impact économique.Cancer/Radiotherapie. 2016; 20: 299-303https://doi.org/10.1016/j.canrad.2016.04.005Crossref Scopus (4) Google Scholar, since on average each travel costs 62€. Patients would finish their RT sooner, which is more convenient. For either older patients or those coming from rural places, hypoRT becomes a “must have,” if given the choice 15Sigurdson S. Harrison M. Pearce A. Richardson H. Zaza K. Brundage M. One fraction size does not fit all: patient preferences for hypofractionated radiation therapy from a discrete choice experiment.Pract Radiat Oncol. 2022; 12: e24-e33https://doi.org/10.1016/j.prro.2021.08.012Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar. However, this lower attendance leads to decreased opportunities for seeking support or engaging with other services. There are cancer sites for which long-term data are still lacking concerning efficacy and secondary effects 16Shakespeare T.P. Westhuyzen J. Fai T.L.Y. Aherne N.J. Choosing between conventional and hypofractionated prostate cancer radiation therapy: results from a study of shared decision-making.Rep Pract Oncol Radiother. 2020; 25: 193https://doi.org/10.1016/J.RPOR.2019.12.028Crossref Google Scholar17“Hypofractionated radiotherapy - British Institute of Radiology.” https://www.bir.org.uk/media-centre/position-statements-and-responses/hypofractionated-radiotherapy/(accessed Nov. 17, 2022).Google Scholar. Additionally, a few things need to be considered:•When patients are first confronted with RT, rarely do they know beforehand that it entails many fractions and will take several weeks to conclude 18Chapman N.A. Oultram S.C. Jovanovic K. Radiation therapy education for rural and remote GPs.Rural Remote Health. 2008; 8: 888https://doi.org/10.22605/rrh888Crossref Google Scholar. So the “shorter duration for same long term result” argument might become redundant on a subjective patient level.•Since hypoRT is considered “non-conventional,” patients may need to give their consent, based on the “shorter duration but higher risk for short-term radiation induced irritations and unclear long-term results” chance. Although many studies have shown that hypoRT may in fact be better tolerated than convRT 19Kawaguchi H. et al.Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery.Jpn J Clin Oncol. 2019; 49: 545-553https://doi.org/10.1093/jjco/hyz003Crossref Scopus (4) Google Scholar, 20Campbell G. Pearse M. Frampton C. A prospective study of cosmetic outcomes for patients treated with breast conservation and radiation therapy using shorter fractionation schedules at Auckland Hospital, New Zealand.Clin Oncol. 2020; 32: 221-227https://doi.org/10.1016/j.clon.2019.10.003Abstract Full Text Full Text PDF Scopus (0) Google Scholar, 21Lertbutsayanukul C. Pitak M. Ajchariyasongkram N. Rakkiet N. Seuree F. Prayongrat A. Long-term patient-rated cosmetic and satisfactory outcomes of early breast cancer treated with conventional versus hypofractionated breast irradiation with simultaneous integrated boost technique.Breast J. 2020; 26 (Oct): 1946-1952https://doi.org/10.1111/tbj.13960Crossref Scopus (5) Google Scholar, 22Pryor D.I. et al.Evaluation of hypofractionated radiation therapy use and patient-reported outcomes in men with nonmetastatic prostate cancer in Australia and New Zealand.JAMA Netw Open. 2021; 4https://doi.org/10.1001/jamanetworkopen.2021.29647Crossref Scopus (5) Google Scholar, 23Köksal M. et al.Late toxicity-related symptoms and fraction dose affect decision regret among patients receiving adjuvant radiotherapy for head and neck cancer.Head Neck. 2022; (May)https://doi.org/10.1002/hed.27103Crossref Scopus (1) Google Scholar, all a person's symptoms, even the irrelevant ones, will be automatically attributed to hypoRT, leading to a perhaps an undeserved and exaggerated reputation, especially when doctors tend to underestimate patient symptoms 24Rammant E. et al.Patient- versus physician-reported outcomes in prostate cancer patients receiving hypofractionated radiotherapy within a randomized controlled trial.Strahlentherapie und Onkol. 2019; 195 (May): 393-401https://doi.org/10.1007/s00066-018-1395-yCrossref PubMed Scopus (29) Google Scholar. Hospital management in both private and public settings, would, at first, raise their concerns, to say the least, against wide, horizontal use of hypoRT. However, the first impression of hypoRT being a simple loss of money from an income point of view, is not completely true. If indeed the 8 Table 3 cancer sites are treated with hypoRT, then about 33% less fractions would be needed. This 1/3 reduction of fractions can automatically be translated as 1/3 less “RT product” produced, but also 1/3 less expenses associated to it:•lower linear accelerator maintenance costs (if 150 K€ per year at an initial usage of 100%, then a usage of 2/3 would result in 50 K€ gain per accelerator) and longer accelerator renewal periods (if each accelerator costs 2.5 M€ and if initial renewal would be every 12 to 15 years, then a usage of 2/3 would add another 50% to duration, so renewal every 18 to 22.5 years - from 55.5 K€ to 69.5 K€ per year) and•less personnel shifts and, thus, less salary expenses, when, at the same time, the remaining personnel will be, at least in theory, happier only working during morning and afternoon and not into the night. At the same time, one of the main hospital quality indicators, the waiting list, will substantially improve, since with convRT some patients needing RT face several weeks of waiting for an appointment 25Nilssen Y. et al.Decreasing waiting time for treatment before and during implementation of cancer patient pathways in Norway.Cancer Epidemiol. 2019; 61 (Aug): 59-69https://doi.org/10.1016/j.canep.2019.05.004Crossref Scopus (15) Google Scholar26Osowiecka K. Nawrocki S. Kurowicki M. Rucinska M. The waiting time of prostate cancer patients in Poland.Int J Environ Res Public Health. 2019; 16 (Feb)https://doi.org/10.3390/ijerph16030342Crossref Scopus (8) Google Scholar, sometimes resulting in lower tumour control 27Jiang Y.T. et al.Prognostic significance of wait time for radical radiotherapy in locoregionally advanced nasopharyngeal carcinoma.Head Neck. 2022; 44 (May): 1182-1191https://doi.org/10.1002/hed.27011Crossref Scopus (2) Google Scholar. Last but not least, fewer patients per day will likely result in less waiting time once the patient is already at the RT department waiting for their turn, resulting in happier patients, personnel and transporters alike 28Lamba N. Niemierko A. Martinez R. Leland P. Shih H.A. The interaction of waiting time and patient experience during radiation therapy: a survey of patients from a tertiary cancer center.J Med Imaging Radiat Sci. 2020; 51 (Elsevier Inc.Mar. 01): 40-46https://doi.org/10.1016/j.jmir.2019.08.008Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar. Less fractions per patient will result in less patients per day and, thus, less total daily working time of the department. RT personnel will likely feel relieved to no longer work late hours (and probably having one or two fewer patients per hour), resulting in better patient care and less work-related stress 29Shields M. James D. McCormack L. Warren-Forward H. Burnout in the disciplines of medical radiation science: a systematic review.J Med Imaging Radiat Sci. 2021; 52 (Elsevier Inc.Jun. 01): 295-304https://doi.org/10.1016/j.jmir.2021.04.001Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar. Nevertheless, they should also feel a bit concerned about their work stability and usefulness 30Melidis C. Merciadri A. Orabona P. COVID-19 cancer recommendation consequences on one radiation therapy department economics and employee working conditions’ satisfaction in France.Hea. Sci. 2020; 2020 (Oct)https://doi.org/10.15342/hs.2020.220Crossref Google Scholar, since the hospital management might realise that less shifts are now needed and, thus, relocate some of them in other departments that may need them more. However, their high specialisation may prevent this. On the other hand, paramedical companies offering parallel, out-of-hospital services directly linked with RT will see their turnover decrease. Patient transportation companies would lose 121.8 M€ per year just in France, while patient accommodation services would decrease by 300 nights per million inhabitants, if we consider a mere 1% of patients using them, based on the 2 million less fractions per 67.25 million people in France. HypoRT, which is becoming the golden standard at least for breast and prostate, represents a non-negligible gain for payers, even if only used in 8 cancer sites. However, its horizontal utilization needs to take many variables into consideration. Besides older patients or those coming from rural areas, all other health stakeholders may find it either restraining or without real interest. There are also various ethical and practical concerns to consider in the long run 30Melidis C. Merciadri A. Orabona P. COVID-19 cancer recommendation consequences on one radiation therapy department economics and employee working conditions’ satisfaction in France.Hea. Sci. 2020; 2020 (Oct)https://doi.org/10.15342/hs.2020.220Crossref Google Scholar31Melidis C. Vantsos M. Ethical and practical considerations on cancer recommendations during COVID‑19 pandemic.Mol Clin Oncol. 2020; 13: 5https://doi.org/10.3892/mco.2020.2075Crossref Scopus (3) Google Scholar. Nevertheless, its undeniable ease of implementation, along with other potential benefits, make it imperative for more research on the subject,. A fully economic cost-benefit analysis could be financed by the direct SSS gains.

Feasibility and first results of the ‘Trials-within-Cohorts’ (TwiCs) design in patients undergoing radiotherapy for lung cancer

Background: ‘Trials-within-Cohorts’ (TwiCs), previously known as ‘cohort multiple randomized controlled trials’ is a pragmatic trial design, supporting an efficient and representative recruitment of patients for (future) trials. To our knowledge, the ‘COhort for Lung cancer Outcome Reporting and trial inclusion’ (COLOR) is the first TwiCs in lung cancer patients. In this study we aimed to assess the feasibility and first year results of COLOR.Material and Methods: All patients diagnosed with lung cancer referred to the Radiotherapy department were eligible to participate in the ongoing prospective COLOR study. At inclusion, written informed consent was requested for use of patient data, participation in patient-reported outcomes (PROs), and willingness to participate in (future) trials. Feasibility was studied by assessing participation and comparing baseline PROs to EORTC reference values. First-year results of PROs at baseline and 3 months after inclusion were evaluated separately for stereotactic body radiotherapy (SBRT) and conventional radiotherapy patients.Results: Of the 338 eligible patients between July 2020 and July 2021, 169 (50%) participated. Among these, 127 (75%) gave informed consent to PROs participation and 110 (65%) were willing to participate in (future) trials. The inclusion percentage dropped from 77% to 33% when the information procedure was switched from in-person to by phone (due to COVID-19 pandemic measures). Baseline PROs for physical and cognitive functioning were comparable in COLOR patients compared to the EORTC reference values. No significant changes in PROs were observed 3 months after inclusion, except for a slight increase in pain scores in the SBRT group (n = 97).Conclusions: The TwiCs-design appears feasible in lung cancer patients with fair participation rates (although negatively impacted by the COVID-19 pandemic). With a planned expansion to other centers, the COLOR-study is expected to enable multiple (randomized) evaluations of experimental interventions with important advantages for recruitment, generalizability, and long-term outcome data collection.

Costs of Newly Funded Proton Therapy Using Time-Driven Activity-Based Costing in The Netherlands.

Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended.

EE482 Costs of Proton Therapy During the Start-up Phase Using Time-Driven Activity-Based Costing in the Netherlands

Proton beam therapy (PBT) aims to deliver precise treatment compared with conventional radiotherapy for patients with cancer. While this innovation entails investment costs, information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs for PBT at a single center in the Netherlands during the start-up phase.

Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: An ancillary study of the PROstate fractionated irradiation trial – PROFIT

PurposeTo evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa). MethodsA prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer’s perspective, with a time horizon of 48 months.Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY).We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap. ResultsTotal costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: − 0.016 to 0.099). ConclusionsTreating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.

Gamma Knife radiosurgery as primary treatment of low-grade brainstem gliomas: A systematic review and metanalysis of current evidence and predictive factors.

The current standard of care for surgically inaccessible low-grade brainstem gliomas (BS-LLGs) is external-beam radiotherapy (RT). Developments toward more innovative conformal techniques have focused on decreasing morbidity, by limiting radiation to surrounding tissues. Among these Gamma Knife radiosurgery (SRS-GK) has recently gained an increasingly important role in the treatment of these tumors. Although SRS-GK has not yet been compared with conventional RT in patients harboring focal BS-LGGs, clinical practice has been deeply influenced by trials performed on other tumors. This is the first meta-analysis on the topic, systematically reviewing the most relevant available evidence, comparing RT and SRS-GK as primary treatments of BS-LGGs, focusing on survival, clinical outcome, oncological control, and complications. Predictive factors have been systematically evaluated and analyzed according to statistical significance and clinical relevance.

A meta-analysis comparing stereotactic body radiotherapy vs conventional radiotherapy in inoperable stage I non-small cell lung cancer.

Stereotactic body radiotherapy (SBRT) superseded conventional radiotherapy (CRT) for the treatment of patients with inoperable early stage non-small cell lung cancer (NSCLC) over a decade ago. However, the direct comparisons of the outcomes of SBRT and CRT remain controversial. This meta-analysis was performed to compare the survival and safety of SBRT and CRT in patients with inoperable stage I NSCLC. We systematically searched the Cochrane Library, Embase, PubMed, Web of Science, Ovid MEDLINE, ScienceDirect, Scopus and Google Scholar for relevant articles. Overall survival (OS), progression-free survival (PFS), lung cancer-specific survival (LCSS), local control rate (LCR) and adverse effects (AEs) were the primary outcomes. We identified 11,110 articles, 17 of which were eventually included in this study; these 17 articles had 17,973 patients (SBRT: 7395; CRT: 10,578). Compared to CRT for the treatment of inoperable stage I NSCLC, SBRT had superior survival in terms of OS (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.62-0.70, P < .00001), LCSS (HR: 0.42 [0.35-0.50], P < .00001), and PFS (HR: 0.34 [0.25-0.48], P < .00001). The 4-year OS rate (OSR); 4-year LCSS rate (LCSSR); 3-year local control rate (LCR); 5-year PFS rate (PFSR) with SBRT were all higher than those with CRT. With regard to all-grade AEs, the SBRT group had a significantly lower rate of dyspnea, esophagitis and radiation pneumonitis; no significant difference was found in grade 3-5 AEs (risk ratio [RR]: 0.68 [0.30-1.53], P = .35). With better survival and a lower rate of dyspnea, esophagitis and radiation pneumonitis than CRT, SBRT appears to be more suitable for patients with inoperable stage I NSCLC.

Hypofractionated radiotherapy versus conventional radiotherapy in patients with intermediate- to high-risk localized prostate cancer: a meta-analysis of randomized controlled trials

BackgroundProstate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.MethodsRelevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses.ResultsThe meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93–1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42–3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76–1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12–2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61–0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89–1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86–1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups.ConclusionResults suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.

Analysis of prognostic factors and patterns of failure in patients of oropharyngeal squamous cell carcinoma treated by definitive radiotherapy in a tertiary care cancer center of Northern India

Background: The incidence of oropharyngeal carcinoma is increasing despite decline in the incidence of head and neck cancers of other sites. Functional organ preservation with minimal toxicity and better survival is the management goal in oropharyngeal cancers (OPCs). Morbidity of surgery favors radiotherapy as primary modality in OPCs. Here, we have reviewed and analyzed various prognostic factors and results of conventional radiotherapy in patients treated at our institute with two-dimensional planning. Materials and Methods: The records of 70 patients who were treated radically with radiotherapy with or without concurrent chemotherapy from January 2014 to May 2018 were analyzed in our institute. Results: The median age was 61.5 years with male:female ratio of 6:1. History of tobacco use was present in 83%. Stage IVA comprised the bulk with 63% of cases. Eighty-one percent of the patients received concurrent cisplatin. Median disease-free survival at 1 and 5 years was 71.4% and 54.3%, respectively. Median overall survival at 1 and 5 years was 74.3% and 60%, respectively. Conclusion: Varied patient-related, tumor-related, and treatment-related factors determine the clinical severity and tumor stage and help in predicting survival in oropharyngeal carcinoma.

Results of a multicentre randomised controlled trial of cochlear-sparing intensity-modulated radiotherapy versus conventional radiotherapy in patients with parotid cancer (COSTAR; CRUK/08/004)

PurposeAbout 40–60% of patients treated with post-operative radiotherapy for parotid cancer experience ipsilateral sensorineural hearing loss. Intensity-modulated radiotherapy (IMRT) can reduce radiation dose to the cochlea. COSTAR, a phase III trial, investigated the role of cochlear-sparing IMRT (CS-IMRT) in reducing hearing loss. MethodsPatients (pT1-4 N0-3 M0) were randomly assigned (1:1) to 3-dimensional conformal radiotherapy (3DCRT) or CS-IMRT by minimisation, balancing for centre and radiation dose of 60Gy or 65Gy in 30 daily fractions. The primary end-point was proportion of patients with sensorineural hearing loss in the ipsilateral cochlea of ≥10 dB bone conduction at 4000 Hz 12 months after radiotherapy compared using Fisher's exact test. Secondary end-points included hearing loss at 6 and 24 months, balance assessment, acute and late toxicity, patient-reported quality of life, time to recurrence and survival. ResultsFrom Aug 2008 to Feb 2013, 110 patients (54 3DCRT; 56 CS-IMRT) were enrolled from 22 UK centres. Median doses to the ipsilateral cochlea were 3DCRT: 56.2Gy and CS-IMRT: 35.7Gy (p < 0.0001). 67/110 (61%) patients were evaluable for the primary end-point; main reasons for non-evaluability were non-attendance at follow-up or incomplete audiology assessment. At 12 months, 14/36 (39%) 3DCRT and 11/31 (36%) CS-IMRT patients had ≥10 dB loss (p = 0.81). No statistically significant differences were observed in hearing loss at 6 or 24 months or in other secondary end-points including patient-reported hearing outcomes. ConclusionCS-IMRT reduced the radiation dose below the accepted tolerance of the cochlea, but this did not lead to a reduction in the proportion of patients with clinically relevant hearing loss.

Clinical results of accelerated hypofractionated radiotherapy for central-type small lung tumours.

We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (ahypof-rt) for central-type small lung tumours. Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent ahypof-rt delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5-3 Gy. A total dose of 69-75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan-Meier method. The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60-87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11-49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively; the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients; no other severe adverse events (≥grade 3) were observed in any patient. Accelerated hypofractionated radiotherapy using a fraction size of 2.5-3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours.

Intensity-modulated radiotherapy provides better quality of life than two-dimensional conventional radiotherapy for patients with stage II nasopharyngeal carcinoma.

Two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated radiotherapy (IMRT) are effective for control of nasopharyngeal carcinoma (NPC). The purpose of this study was to compare the quality of life (QoL) of stage II NPC patients treated with 2D-CRT versus IMRT. We conducted a cross-sectional study of 106 patients with stage II NPC treated with 2D-CRT (n = 47) versus IMRT (n = 59) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. Patients receiving IMRT with or without concurrent chemotherapy had better outcomes in head and neck related symptoms and general aspects of QoL than those receiving 2D-CRT with or without concurrent chemotherapy. Thus, IMRT improves the QoL of patients with stage II NPC as compared to 2D-CRT.

Radiation-induced toxicity after image-guided and intensity-modulated radiotherapy versus external beam radiotherapy for patients with spinal bone metastases (IRON-1): a study protocol for a randomized controlled pilot trial

BackgroundRadiation therapy (RT) of bone metastases provides an important treatment approach in palliative care treatment concepts. As a consequence of treatment, the extent of radiation-induced toxicity is a crucial feature with consequences to a patient’s quality of life. In this context this study aims at reducing the extent of radiation-induced side effects and toxicity by assuming a better sparing of normal tissue with the use of intensity-modulated instead of conventionally delivered external beam radiotherapy.Methods/designIn this prospective, randomized, single-center trial for patients with spinal bone metastases, RT is performed as either image-guided intensity-modulated radiotherapy (10x3Gy) or conventionally fractionated external beam radiotherapy (10x3Gy). Afterwards radiation-induced toxicity will be assessed and compared 3 and 6 months after the end of radiation.DiscussionThe aim of this pilot study is the evaluation of achievable benefits, with reduced radiation toxicity being the primary endpoint in the comparison of intensity-modulated radiotherapy versus conventional radiotherapy for patients with spinal bone metastases. Secondarily, bone re-calcification, quality of life, pain relief, spinal instability, and local control will be measured and compared between the two treatment groups.Trial registrationClinicalTrials.gov, NCT02832830. Registered on 12 July 2016.

Breastdosimetry of 99mTc-balloon in complementary radiotherapy

Dose reinforcement in primary tumor cavity can complement conventional radiotherapy in patients with early breast cancer. In this study, a dosimetric analysis was conducted by pertechnetate-99mTc-filled balloon brachytherapy (TBB). MethodsDosimetry based on radiochromic films and on a computational voxel thorax model was performed. Calibration protocol achieved a mathematical relationship between dose and optical density in films placed on the surface at a distance of 0–9cm, 1cm between them, in which dose values were provided by MCNP® code. Moreover, experimental spatial dose distribution was prepared. A female thorax voxel model was developed in the SISCODES®/MCNP® codes. Additionally, experimental and computational doses at 8–10mm from balloon surface were compared. ResultsDose from 99mTc-balloon, with 16mm diameter, 32.22GBq activity, and 24h exposure time, achieved 8.08±0.42 (Ue) and 8.82±1.76 (Ue) Gy, at a distance of 10mm from the balloon surface for the experimental data and computational modeling, respectively, thus showing nonsignificant difference. The spatial dose distribution in the chest wall, glandular tissue, breast skin, and lung was presented. The dosimetric findings supported the TBB modality presenting a suitable spatial dose distribution in the tumor bed and preserving the adjacent health tissues. ConclusionTBB is a viable adjuvant brachytherapy modality for breast cancer in patients who have an appropriate indication.

Aspiration as a late complication after accelerated versus conventional radiotherapy in patients with head and neck cancer

Conclusion Neck dissection after radiotherapy increased the risk of aspiration as a late effect in a sub-sample of patients treated for head and neck cancer in the ARTSCAN study. Patients treated with accelerated fractionation (AF) developed aspiration, with or without coughing, more frequently than patients treated with conventional fractionation (CF). Objectives A long-term follow-up study was conducted to determine the frequency of aspiration as a late effect in patients with head and neck cancer treated with AF or CF. Method One-hundred and eight patients were recruited from two centres of the Swedish multi-centre study, ARTSCAN, where AF and CF were compared. Patients with positive lymph nodes were treated with neck dissection after completing radiotherapy. The follow-up was performed at a median of 65 months after initiation of radiotherapy and included an ENT and a videofluoroscopic examination. Results Aspiration was found in 51/108 (47%) and silent aspiration in 34/96 (35%) patients. Neck dissection (n = 47 patients) was significantly associated with both aspiration and silent aspiration. Aspiration was more common among patients treated with AF (34/61; 56%) compared to CF (17/47; 36%; p = 0.053). Silent aspiration was also more common after AF (24/54; 44%) than after CF (10/42; 24%; p = 0.052).

Pulmonary radiofrequency ablation (Part 1): Current state

The risks involved in surgical treatment and conventional radiotherapy in patients with early lung cancer or lung metastases often make these treatments difficult to justify. However, on the other hand, it is also unacceptable to allow these lesions to evolve freely because, left untreated, these neoplasms will usually lead to the death of the patient. In recent years, alternative local therapies have been developed, such as pulmonary radiofrequency ablation, which has proven to increase survival with a minimal risk of complications. There are common recommendations for these treatments, and although the specific indications for using one technique or another have yet to be established, there are clearly defined situations that will determine the outcome of the treatment. It is important to know these situations, because appropriate patient selection is essential for therapeutic success. This article aims to describe the characteristics and constraints of pulmonary radiofrequency ablation and to outline its role in thoracic oncology in light of the current evidence.

Radiofrecuencia pulmonar (parte 1): Estado actual

The risks involved in surgical treatment and conventional radiotherapy in patients with early lung cancer or lung metastases often make these treatments difficult to justify. However, on the other hand, it is also unacceptable to allow these lesions to evolve freely because, left untreated, these neoplasms will usually lead to the death of the patient. In recent years, alternative local therapies have been developed, such as pulmonary radiofrequency ablation, which has proven to increase survival with a minimal risk of complications. There are common recommendations for these treatments, and although the specific indications for using one technique or another have yet to be established, there are clearly defined situations that will determine the outcome of the treatment. It is important to know these situations, because appropriate patient selection is essential for therapeutic success. This article aims to describe the characteristics and constraints of pulmonary radiofrequency ablation and to outline its role in thoracic oncology in light of the current evidence.

Iodine-125 brachytherapy improved overall survival of patients with inoperable stage III/IV non-small cell lung cancer versus the conventional radiotherapy.

This study compared the efficacy of iodine-125 seed brachytherapy versus the conventional radiotherapy in patients with non-resectable stage III/IV non-small cell lung cancer. A total of 71 patients with inoperable advanced stages of lung cancer with tumor size ranging 5-10cm were randomly assigned into two groups: Group A received the regional iodine-125 implantation (n=35), and Group B received the conventional radiotherapy (n=36). The isodose curves were obtained by the treatment planning system for patients in Group A. Postoperative tumor size, clinical symptoms, and quality of life were then assessed. The overall response rate (complete response+partial response) was 88 and 59% in Group A and Group B, respectively. Moreover, patients receiving iodine-125 implantation had higher one- or two-year survival rates than those patients receiving radiation therapy (P<0.05). For patients with a large tumor, iodine-125 implantation significantly ameliorated the clinical symptoms and improved quality of life compared with the conventional radiotherapy and chemotherapy. Iodine-125 implantation treatment was more effective to control inoperable, large lung cancer and improved overall survival and quality of life compared with the conventional radiotherapy and chemotherapy.

Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

BackgroundHealth-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy.MethodsA total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle.ResultsOn the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective.At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA with the Bonferroni correction did not show any significant differences between groups in HRQOL scores.ConclusionsTT patients had a better improvement in global health status and role- and cognitive-functioning, and a faster recovery from fatigue, than CR patients. These results suggest that a shorter fractionation schedule may reduce the adverse effects of treatment.