To investigate the local control (LC) and overall survival (OS) rates of patients with T2N0M0 carcinoma of the glottis (TNM 7th edition) treated exclusively with radiotherapy.

To compare the treatment outcome and toxicity between patients with stage IVA (TNM 7th edition) squamous cell carcinoma of the tonsil treated with either primary (chemo)radiation therapy or surgery followed by adjuvant (chemo)radiation therapy. Between March 2009 to February 2013, 52 consecutive patients with a biopsy-proven squamous cell carcinoma of the tonsil, stage IVA (TNM 7th edition), were analyzed retrospectively. Group CRT (primary radiation therapy ± chemotherapy, n=37) was compared against group S+CRT (surgery followed by adjuvant radiation therapy ± chemotherapy, n=15). The two groups were well-matched in terms of patient’s age (median age 57 years in group CRT vs 60 in group S+CRT), HPV status (54% vs 60% positive, 16% vs 20% negative, and 30% vs 20% not available). However, the number of patients with T1/2 was higher in group S+CRT (80% vs 54%) and more patients received concurrent chemotherapy in group CRT (89% vs 60%). The radiation therapy regime was 63- 65 Gy in 30 daily fractions ± weekly cisplatin (40mg/m2) chemotherapy or cetuximab (loading dose 400mg/m2 followed by weekly 250mg/m2) biotherapy. In group CRT, complete response (CR) was achieved in 97% patients (in 1 patient, CR was not achieved). Out of 36 patients with response, 2 patients (6%) developed locoregional recurrences (LRR) and 3 patients (8%) developed distant metastases (DM). This was comparable to group S+CRT (7% LRR and 7% DM). With a median follow-up of 51 months, 29 patients in CRT group were alive (5 out of the total of 8 deaths were disease related). In S+CRT group, 14 patients were alive and 1 died of disease. Five-year disease specific survival (DSS) was 88% in CRT group versus 93% in S+CRT group (HR 0.60; 95% CI 0.09-4.0). The difference in overall survival was not statistically significant. Addition of chemo(bio)therapy influenced the outcome (P=.02). HPV status (P=.83), age (P=.41) and number of cycles of chemotherapy received (P=.16) were not significant variables. There was a trend of less acute toxicities (grade 3 mucositis was 27% vs 54%, P=.068), and hospital admission rate (27% vs 49%, P=.21) in group S+CRT, but it was not statistically significant. There was no statistically significant difference in incidence of late effects in two groups (we assessed esophageal, soft tissue, bone, salivary gland and laryngeal toxicity). This retrospective analysis has not confirmed any significant difference in the outcome of definitive (chemo)radiation therapy versus combined modality treatment in patients with locoregionally advanced carcinoma of the tonsil. Although the TNM 8th edition has been updated based on HPV status, our analysis did not show HPV status as a significant variable.

Background: Primary small cell neuroendocrine carcinoma of larynx is a rare, aggressive type of malignancy. As only about 200 cases worldwide have been reported, any larger institutional experience is valuable. This study reports our experience in managing this rare entity.Methods: Of the nine patients identified, three had metastatic cancer at the time of diagnosis. Four patients underwent radical treatment: one was managed surgically followed by adjuvant chemotherapy and consolidation radiotherapy; the remaining three were treated with neoadjuvant chemotherapy and definitive radiotherapy.Results: Of the 4 patients treated with radical intent, 1 was alive and disease free after 99 months, 2 died of metastatic disease after 22 and 26 months, and 1 was alive after 20 months with a diagnosis of recurrent disease.Conclusion: Our relatively small number of patients confirms other centres' experiences. This cancer has a poorer prognosis than most other head and neck cancers. Although the logistics would be challenging, there is a need for international multicentre trials for this disease modelled on those performed for other cancers, as has been done for paediatric malignancies.

Purpose of the study: Older patients with head and neck cancer may be denied the potentially beneficial addition of chemotherapy to primary radiotherapy in the management of head and neck cancer, because of fears that older patients will develop relatively more treatment related morbidity and not tolerate treatment, when compared to younger patients. This could lead to breaks in, or discontinuation of radiotherapy giving poorer outcomes for survival and local control in older patients.

OBJECTIVE:Intensity-modulated radiotherapy (IMRT) is increasingly being used to treat head and neck cancer cases.METHODS:We discuss the clinical challenges associated with the setting up of an image guided intensity modulated radiotherapy service for a subset of head and neck cancer patients, using a recently commissioned helical tomotherapy (HT) Hi Art (Tomotherapy Inc, WI) machine in this article. We also discuss the clinical aspects of the tomotherapy planning process, treatment and image guidance experiences for the first 10 head and neck cancer cases. The concepts of geographical miss along with tomotherapy-specific effects, including that of field width and megavoltage CT (MVCT) imaging strategy, have been highlighted using the first 10 head and neck cases treated.RESULTS:There is a need for effective streamlining of all aspects of the service to ensure compliance with cancer waiting time targets. We discuss how patient toxicity audits are crucial to guide refinement of the newly set-up planning dose constraints.CONCLUSION:This article highlights the important clinical issues one must consider when setting up a head and neck IMRT, image-guided radiotherapy service. It shares some of the clinical challenges we have faced during the setting up of a tomotherapy service. Implementation of a clinical tomotherapy service requires a multidisciplinary team approach and relies heavily on good team working and effective communication between different staff groups.

Aims: To compare the treatment outcome priorities of patients, their companions and members of the multidisciplinary team (MDT), and also to determine if the former two groups suffered from regret of their decision.Materials and methods: Patients were eligible if attending with a companion at least 6 months after radiotherapy for head and neck cancer given with curative intent. They were interviewed by two clinicians separately with questions from the Chicago Priority Scale and Ottawa Decision Regret Scale.Results: In total, 30 patients, 30 companions and 25 members of the MDT were evaluated. 'Being cured of my cancer', 'living as long as possible', 'having no pain' and 'being able to swallow all foods and drinks' were the top four priorities for all three groups. Patients ranked 'having no pain' lower than either companions (P = 0.003) and members of the MDT (P = 0.006). Patients ranked 'keeping my appearance unchanged' as less important than members of the MDT (P = 0.013) and 'keeping my normal sense of taste and smell' as more important than members of the MDT (P = 0.013). The post-treatment regret score was 12.50 for patients and 10.33 for companions out of 100 (P value was not significant).Conclusions: There was a strong agreement between patients, their companions and members of the MDT with regards to priorities in head and neck cancer outcomes and low post-treatment regret for patients and their companions. These results suggest that the patients' companions and members of the MDT are able to exercise good judgment when it comes to supporting patients in decision making. (C) 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background and purpose: An increased therapeutic index has been achieved using IMRT [1]; trials have started exploring dose escalation strategies in head and neck cancers in order to achieve higher tumour control probability. The proximity of oropharynx to organs at risk (OAR), like the parotids and muscles of swallowing and mastication, makes dose escalation challenging. Vortigern study analyses target volume definition based on CT versus PET CT and explores the feasibility of dose escalation in oropharyngeal cancer.

Aims Contrast-enhanced computed tomography (CECT) is the current standard for delineating tumours of the head and neck for radiotherapy. Although metabolic imaging with positron emission tomography (PET) has been used in recent years, the studies were non-confirmatory in establishing its routine role in radiotherapy planning in the modern era. This study explored the difference in gross tumour volume and clinical target volume definitions for the primary and nodal volumes when FDG PET/CT was used as compared with CECT in oropharyngeal cancer cases. Materials and methods Twenty patients with oropharyngeal cancers had a PET/CT scan in the treatment position after consent. Target volumes were defined on CECT scans by a consultant clinical oncologist who was blind to the PET scans. After obtaining inputs from a radiologist, another set of target volumes were outlined on the PET/CT data set. The gross and clinical target volumes as defined on the two data sets were then analysed. The hypothesis of more accurate target delineation, preventing geographical miss and comparative overlap volumes between CECT and PET/CT, was explored. The study also analysed the volumes of intersection and analysed whether there was any TNM stage migration when PET/CT was used as compared with CECT for planning. Results In 17 of 20 patients, the TNM stage was not altered when adding FDG PET information to CT. PET information prevented geographical miss in two patients and identified distant metastases in one case. PET/CT gross tumour volumes were smaller than CECT volumes (mean ± standard deviation: 25.16 cm3 ± 35.8 versus 36.56 cm3 ± 44.14; P < 0.015) for the primary tumour. Interestingly, our study showed no significant differences in gross tumour volume for T1/T2 disease, although differences in gross tumour volumes for advanced disease (T3/T4) were significant. The nodal target volumes (mean ± standard deviation: CECT versus PET/CT 32.48 cm3 ± 36.63 versus 32.21 cm3 ± 37.09; P > 0.86) were not statistically different. Similarity and discordance coefficients were calculated and are reported. Conclusion PET/CT as compared with CECT could provide more clinically relevant information and prevent geographical miss when used for radiotherapy planning for advanced oropharyngeal tumours. Also, PET/CT provided a smaller better-defined target volume when compared with CECT. PET/CT-based volumes could therefore be used for treatment planning and targeted dose painting in oropharyngeal cancers.

Free AccessCorrespondenceExtensive basal cell carcinoma of the forehead and anterior scalp: use of helical tomotherapy as a radiotherapy treatment modalityS Chatterjee, J H Mott, S Dickson and C G KellyS ChatterjeeNorthern Centre for Cancer Care, Freeman Hospital Freeman Road, Newcastle upon Tyne, NE7 7DN, UK , J H MottRegional Medical Physics Department, Freeman Hospital Freeman Road, Newcastle upon Tyne, NE7 7DN, UK , S DicksonNorthern Centre for Cancer Care, Freeman Hospital Freeman Road, Newcastle upon Tyne, NE7 7DN, UK and C G KellyNorthern Centre for Cancer Care, Freeman Hospital Freeman Road, Newcastle upon Tyne, NE7 7DN, UK Published Online:28 Jan 2014https://doi.org/10.1259/bjr/64114980SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail AboutEditor — Sir,We present the first case in the literature of an extensive basal cell carcinoma of the forehead that has been managed with helical tomotherapy (HT). A 95-year-old lady had first presented in 2004 but had refused surgery. She re-presented with extensive local disease in 2009, at which time the tumour in the forehead was extending to the scalp in close proximity to the optic apparatus.Surgery was thought to be too extensive and quite challenging, given the site of disease. Photodynamic therapy (PDT) was considered, but owing to the thickness of the tumour, extensive nature of disease and proximity to critical organs was considered inappropriate 1. Radiotherapy was therefore the treatment of choice.Despite the very challenging geometry, HT was able to create and deliver a plan, giving high dose to a complex target with excellent sparing of adjacent critical organs, including the optic apparatus. The patient was examined by the treating physician in the presence of mould room staff, treatment planning dosimetrists and a physicist in order to determine the best way to set up and scan the patient for treatment with HT.The head and neck were immobilised using a customised beam directional shell (BDS) made of polyethylene terephthalate glycol (PTEG). The shell consisted of a custom-made back and front half, attached using the Posifix 5-point fixation system. Wire marks were placed on the BDS to ascertain the extent of the disease on the CT scan and facilitate outlining of the main planning target volume (PTV1) (Fig 1).Figure 1 A surface-rendered image of the patient's CT scan showing wire markers placed to facilitate outlining of PTVs. The red wire frame structure indicates the area covered by bolus. Download Figure The disease extending down between the patient's eyes was outlined as a separate target volume (PTV2) to allow more control over the trade-off between target coverage and lens dose in this region. Organs at risk outlined included the brain, brain stem, bilateral optic nerves, lens, orbits and optic chiasm.The main aim of treatment was to achieve adequate palliation of the lesion, with acceptable toxicities to the adjacent critical structures in this elderly patient. Although BCC is considered to be radiosensitive, given the extent of the disease a dose of 63 Gy in 30 fractions was prescribed to the PTV.There has been some discussion in the literature with regards to the necessity of bolus (Fig 1) when treating with HT 2, 3. As the PTV for this patient extended to the skin surface we chose to add bolus over the target area in order to avoid driving the optimisation in the low dose build-up region.Additional thicknesses of PTEG were vacuum-formed over the original shell to give a total of 5 mm PTEG over the area of the PTV, plus a 5 mm circumferential margin. This approach was found to facilitate adequate coverage of the surface tumour with the prescription dose. Figures 2 and 3 show the isodoses and give the dose volume histogram (DVH) data for the target and critical organs. Despite the difficult geometry of the target volume, 97.5% of the combined PTVs received at least 95% of the prescribed dose (63 Gy).Figure 2 DVH coverage of the PTVs and OARs. Download Figure Figure 3 Axial (a), sagittal (b) and coronal (c) views of the dose distribution. (d), Isosdose wash. Isodoses are in absolute dose (Gy) and show 30, 50, 70, 80, 90, 95, 100 AND 107% of the prescribed dose (63 Gy). Note the homogenous dose distribution in the scalp and sparing of critical organs. Download Figure The chiasm was limited to a maximum dose of 25.9 Gy. Although the PTVs were drawn within 7 mm and 10 mm of the right and left orbits, doses to the right and left lenses of 11.0 Gy and 8.0 Gy, the orbits of 33.8 Gy and 30.5 Gy and the optic nerves of 36.5 Gy and 37.6 Gy were achieved.The choice of appropriate modality (electrons or photons) for treating locally advanced BCC in the forehead necessitates consideration of the proximity of the lesion to nearby eyes, depth of invasion, invasion of underlying bone or cartilage and the convex contour of the forehead and anterior scalp. When treating superficial non-melanoma skin cancers with photons it is common to use lower energies (100–250 Kv) to avoid skin sparing and minimise side-effects resulting from the significant dose to deeper tissues, which is seen with megavoltage energy photons 4.An alternative is to use low energy electrons (6–9 MeV), perhaps with tissue equivalent bolus to increase the surface dose. The treatment of whole scalp lesions with low dose to the brain has been reported using matched electron fields 5. However, such plans may have significant dose inhomogeneity and require complex planning and verification processes 5.The use of intensity-modulated radiotherapy (IMRT), delivered by static segmented linear accelerator-based techniques 4, serial tomotherapy [10] although feasible, the dose to the brain was reported to be higher than the matched electron technique. More recently, helical tomotherapy 7 has also been explored for extensive scalp lesions.Despite not completing the full course of treatment, the palliative requirements of this elderly patient were met. Given the excellent treatment plan achieved in this case, more hypofractionated regimes could be explored in future as palliative treatment in elderly patients with extensive lesions using fewer fractions. Similarly, with potential for an improved therapeutic index, superficial more radio-resistant scalp tumours could also be targeted with a higher radiation dose, to achieve adequate tumour control in the scalp and forehead.References1 Ceilley RI , Del Rosso JQ . Current modalities and new advances in the treatment of basal cell carcinoma. Int J Dermatol 2006;45:489–498. Crossref Medline ISI, Google Scholar2 Khatunia D , Jaradat H , Orton N , Tomé W , Mehta MP , Welsh JS . Helical Tomotherapy as a means of administering total or partial scalp irradiation: In regards to Bwdford et al (Int J Radiat Oncol Biol Phys 2005;62:1549–1558). Int J Radiat Oncol Biol Phys 2006;64:1289–1290. Crossref ISI, Google Scholar3 Hardcastle N , Soisson E , Metcalfe P , Rosenfeld AB , Tome WA . Dosimetric Verification of helical tomotherapy for total scalp irradiation. Med Phys 2008;35:5061–5068. Crossref Medline ISI, Google Scholar4 Bedford JL , Childs PJ , Hansen VN , Warrington AP , Mendes RL , Glees JP . Treatment of extensive scalp lesions with segmental intensity modulated photon therapy. Int J Radiat Oncol Biol Phys 2005;62:1549–1558. Crossref Medline ISI, Google Scholar5 Mellenberg DE , Schoeppel SL . Total scalp treatment of mycosis fungoides: The 4 X 4 technique. Int J Radiat Oncol Biol Phys 1993;27:953–958. Crossref Medline ISI, Google Scholar6 Locke J , Low DA , Grigireit T , Chao KS . Potential of tomotherapy for total scalp treatment. Int J Radiat Oncol Biol Phys 2002;52:553–559. Crossref Medline ISI, Google Scholar7 Orton N , Jaradat H , Welsh J , Tomé W . Total Scalp irradiation using helical tomotherapy. Med Dosim 2005;30:162–168. Crossref Medline ISI, Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byUsefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma28 September 2015 | International Journal of Molecular Sciences, Vol. 16, No. 10Management of advanced non-melanoma skin cancers using helical tomotherapy6 April 2013 | Journal of the European Academy of Dermatology and Venereology, Vol. 28, No. 5Basal Cell Carcinoma30 May 2014 | Deutsches Aerzteblatt OnlineMulti-centre experience of implementing image-guided intensity-modulated radiotherapy using the TomoTherapy platformRadiography, Vol. 19, No. 3Total dural irradiation: RapidArc versus static-field IMRT: A case studyMedical Dosimetry, Vol. 37, No. 2Clinical challenges in the implementation of a tomotherapy service for head and neck cancer patients in a regional UK radiotherapy centreS Chatterjee, J H Mott, G Smyth, S Dickson, W Dobrowsky and C G Kelly5 March 2014 | The British Journal of Radiology, Vol. 84, No. 1000 Volume 83, Issue 990June 2010Pages: 453-e128 2010 The British Institute of Radiology History ReceivedDecember 31,2010AcceptedJanuary 12,2010Published onlineJanuary 28,2014 Metrics Download PDF

To evaluate the feasibility, effectiveness, and long-term bowel function of preoperative hyperfractionated accelerated radiotherapy in primary resectable rectal cancer. A total of 184 consecutive patients (median age 65 years, male : female=2 : 1) with clinical T3Nx rectal adenocarcinoma received preoperative pelvic radiation therapy with single fractions of 2.5 Gy twice daily (interval 6 h between fractions) to a total dose of 25 Gy within 1 week. Surgery was conducted the following week. Postoperative histology revealed UICC stage I in 33%, stage II in 26%, stage III in 34%, and stage IV in 7% of the patients. Median follow-up was 43 months (53 months for surviving patients). The actuarial 4-year-local-recurrence rate was 2.1%, overall recurrence 23%. Disease-specific and disease-free survivals at 4 years (excluding stage IV) were 82 and 69%, respectively. Overall survival for 4 years was 68%. Postoperative mortality was 0.5% (one patient), early anastomotic leakage occurred in 11.4%, and anastomotic stenosis requiring treatment in 6%, of 132 patients with primary anastomosis. Seven of 184 patients (3.8%) died of abdominal complications, all within the first year. Bowel function was satisfactory after more than 5 years. Local control in primarily resectable rectal cancer after 10 x 2.5 Gy is excellent, warranting further evaluation of this treatment.

To investigate efficacy and feasibility of hyperfractionated accelerated radiotherapy combined with mitomycin C, patients with locally advanced unresectable squamous cell carcinomas of the head and neck region were administered 64-66 Gy in four weeks and mitomycin C (20 mg/m(2)) on day five. Twenty-one consecutive patients were included between November 1997 and June 1999 (median age: 57 years). All tumours were stage T3-4 and 18/21 were N2-3. Eighteen patients experienced grade 3 and three patients grade 2 mucosal toxicity. With median follow up for surviving patients of 42 months, loco-regional control was 55% at three years, overall survival was 33% at three years. This treatment is at the edge of local tolerability, but there is a good curative chance even for very advanced localised tumours, provided a complete remission is induced at primary treatment.

The aim of the project was to study the role of altered fractionated radiotherapy (RT) on overall survival and on loco-regional control, as secondary endpoint. Updated individual data from HNSCC patients randomized to conventional RT versus hyperfractionated or accelerated RT were included in this meta-analysis. The logrank-test, stratified by trial, was used for comparison and the hazard ratio (HR) of death or loco-regional failure (LRF) was calculated. Fifteen randomized trials (1970–1998) with 6,515 patients were included. One trial had four-arms and its control group was counted three time in the analysis that was then performed on 7,073 patients. The proportion of patients according to tumor site were: oropharynx, 44%; larynx, 34%; oral cavity, 12%; hypopharynx 8%; other, 2%. The median follow-up period was 6 years. The pooled HR of death was 0.92 (95% confidence interval: 0.87–0.97; p = 0.004) corresponding to an absolute survival benefit of 3% for modified RT, from 36% to 39%, at 5 years. The pooled HR of LRF was 0.82 (0.77–0.88; p < 0.0001) corresponding to an absolute benefit on loco-regional control of 7% for altered RT, from 46% to 53%, at 5 years. Local and regional (nodal) controls were studied on 12 trials (6,410 patients). The absolute benefit on local control was more pronounced (8 %) than on regional control (3%). Four groups of trials were defined according to the total dose in the altered RT arm as compared to the conventional arm : 1) increased (hyperfractionated RT), 4 trials (1,350 patients), 2) similar without acceleration, 2 trials (688 patients), 3) similar with acceleration, 6 trials (3,130 patients), and 4) decreased (very accelerated RT), 5 trials (1,905 patients). There was a significant interaction (p = 0.04) for survival, between the type of RT and the observed effect : the largest effect on survival was observed with increased total dose. A significant interaction (p = 0.03) was also observed on loco-regional control with the largest effects observed with increased total dose and similar dose with acceleration. Altered radiotherapy led to a small but significant improvement in survival and local-regional control. The benefit on survival may dependent on the type of radiotherapy. (Grants from Association Recherche CancersProgramme Hospitalier de Recherche Clinique)

PURPOSE:Tumor cell repopulation is still considered to be a major cause of failure in radiotherapy. In this study, we investigated the influence of cell kinetic parameters on the outcome of patients treated in a randomized trial of accelerated fractionation, with or without mitomycin C, vs. conventional fractionation.METHODS AND MATERIALS:Sixty-two patients were studied using administration of bromodeoxyuridine (BrdUrd), and cell kinetic parameters were measured using flow cytometry. The patients were treated with either 70 Gy for 7 weeks or 55.3 Gy for 17 continuous days (V-CHART) with or without 20 mg/m(2) mitomycin C on day 5.RESULTS:The potential doubling time (Tpot) and labeling index (LI) failed to provide any prognostic information with regard to local control or survival. However, the duration of the S phase (Ts) revealed patients whose tumors had a long Ts had significantly worse local control (p = 0.028) and survival (p = 0.034) irrespective of treatment. A similar trend was evident within the different treatment arms particularly associated with overall survival.CONCLUSIONS:The Ts values of head-and-neck squamous cell cancers provided prognostic information that predicted clinical outcome irrespective of treatment schedule in this study. This neglected parameter of the Tpot method might provide information related to redistribution of cells during fractionated radiotherapy.

Purpose/Objective: The aim of the project was to study the role of modified radiotherapy (RT) on overall survival. Materials/Methods: The Meta-Analysis of Radiotherapy in Carcinomas of Head & Neck (MARCH) group performed a meta-analysis using updated individual patient data comparing conventional RT to hyperfractionated or accelerated RT, or both, as radical treatment, in locally advanced head and neck squamous cell carcinoma Trials including only nasopharyngeal carcinoma were not eligible. The logrank-test, stratified by trial, was used for comparison and the hazard ratio (HR) of death or loco-regional failure (LRF) was calculated. Results: Fifteen randomized trials (1970-1998) with 6,515 patients were included. One trial had four-arms and contributed to three comparisons. Its control group was counted three time in the analysis that was then performed on 7,073 patients. The median follow-up period was 5.8 years. The pooled HR of death was 0.91 (95% confidence interval: 0.86-0.97; p=0.003) corresponding to an absolute survival benefit of 3% for modified RT, from 36% to 39%, at 5 years. The pooled HR of LRF was 0.82 (0.77-0.88; p<0.0001) corresponding to an absolute benefit on loco-regional control of 7% for modified RT, from 46% to 53%, at 5 years. Three groups of trials were defined according to the total dose in the modified RT arm as compared to the conventional arm: increased (hyperfractionated RT), similar (accelerated RT) and decreased (very accelerated RT). There was a significant interaction (p=0.03) for survival, but not for loco-regional control (p=0.14), between the type of RT and treatment effect (table). The largest effect was observed with increased total dose. The heterogeneity of treatment effect between trials disappeared after exclusion of the 3 trials having included less than 110 patients for both endpoints. There was no evidence that any subgroup of patients defined according to tumor site benefited more or less of modified RT than any other group. Conclusions: Modified radiotherapy led to a small but significant improvement in survival and loco-regional control. The benefit on survival is dependent on the type of radiotherapy. Grants from Association Recherche Cancer & Programme Hospitalier de Recherche Clinique. Tabled 1RT type according to total doseTrial numberPatient numberHazard ratio of deathHazard ratio of LRFIncreased41,3500.780.76Similar83,8180.960.80Decreased51,9050.930.91Total177,0730.910.82 Open table in a new tab