Complications and Risk Factors in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy.

INTRODUCTION: Soft tissue sarcomas of the extremities (ESTSs) pose significant challenges in treatment and management due to their diverse nature and potential complications. This study aimed to assess complications associated with multimodal treatments involving surgery and radiotherapy (RT) and to identify potential risk factors. METHODS: We retrospectively analyzed nonmetastatic ESTS patients treated with surgery and pre- or post-operative RT between 2007 and 2020 in Strasbourg, France. Complications, including wound complications (WCs), lymphedema, acute and chronic RT-related complications, and fractures, were meticulously evaluated. RESULTS: A total of 169 patients diagnosed with localized ESTSs were included, with a median age of 64 years (range 21-94 years). ESTSs primarily occurred proximally (74.6%) and in the lower limbs (71%). The median follow-up was 5.5 years. WCs occurred in 22.5% of patients, with proximal and lower extremity tumors being significant risk factors. Acute RT-related complications included radiodermatitis, with grade ≥ 2 occurring in 43.1% of patients, which was associated with superficial tumors. Three patients had an edema grade ≥ 2. Chronic complications included telangiectasias (21.7%) and fibrosis (38.7%), with higher rates associated with larger PTVs and higher RT doses, respectively. Fractures occurred in 5 patients, mainly in the tibia (40%). CONCLUSIONS: Multimodal treatment of ESTSs demonstrated excellent tolerance, with manageable side effects. Numerous risk factors have been highlighted, providing insights for optimizing treatment strategies and enhancing patient care in this rare disease.

Comparative study of dynamic conformal arc therapy and volumetric modulated arc therapy for treating single brain metastases: A retrospective analysis of dosimetric and clinical outcomes.

Background and purpose: Stereotactic radiation therapy (SRT) is commonly used to treat brain metastases (BMs). This retrospective study compared two SRT techniques, dynamic conformal arc therapy (DCAT) and volumetric modulated arc therapy (VMAT), for single BM treatments. Material and methods: Data of patients treated between January 2010 and June 2020 were considered. Patients with multiple BMs, resected BMs, reirradiation, whole-brain radiation therapy and brainstem metastases were excluded. We focused our analysis on 97 patients who received 23.1 Gy in three fractions. Acute toxicities and follow-up outcomes were recorded. Dosimetric data were analyzed in two subgroups (PTV ≤ 10 cc and PTV > 10 cc). Results: DCAT and VMAT were used in 70 (72.2 %) and 27 (27.8 %) patients, respectively. Acute toxicities were not significantly different between groups (p = 0.259), and no difference was detected in the incidence rate of radionecrosis, local recurrence and cerebral recurrence (p > 0.999, p > 0.999 and p = 0.682, respectively). PTV coverage was better with DCAT for small volumes (PTV ≤ 10 cc). Mean conformity index (CI) was significantly higher with VMAT and mean gradient index (GI) was significantly lower with DCAT whatever volume subgroups (p < 0.001). DCAT had more heterogeneous plans and VMAT required more monitor units. DCAT resulted in reduced low and intermediate doses, whereas VMAT led to decreased high doses. Conclusion: DCAT and VMAT are two effective and safe SRT techniques for BMs treatment. In the era of re-irradiation, it is important to reduce the doses delivered to healthy tissues. Further prospective studies are needed to validate these findings.

Factors Influencing Long-Term Local Recurrence, Distant Metastasis, and Survival in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy.

INTRODUCTION: The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. METHODS: We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications. RESULTS: A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21-94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2-3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy4 (range 45.0-109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy4 (p = 0.015). Deep tumors were associated with worse OS (p < 0.05), and grade 2-3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS (p < 0.05). IMRT was associated with longer LC than 3DRT (p = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS (p < 0.05) and that patients with distant relapse had shorter OS (p < 0.0001). CONCLUSION: RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS.

Nuclear medicine imaging methods of early radiation-induced cardiotoxicity: a ten-year systematic review.

Introduction: Radiotherapy has significantly improved cancer survival rates, but it also comes with certain unavoidable complications. Breast and thoracic irradiation, for instance, can unintentionally expose the heart to radiation, leading to damage at the cellular level within the myocardial structures. Detecting and monitoring radiation-induced heart disease early on is crucial, and several radionuclide imaging techniques have shown promise in this regard. Method: In this 10-year review, we aimed to identify nuclear medicine imaging modalities that can effectively detect early cardiotoxicity following radiation therapy. Through a systematic search on PubMed, we selected nineteen relevant studies based on predefined criteria. Results: The data suggest that incidental irradiation of the heart during breast or thoracic radiotherapy can cause early metabolic and perfusion changes. Nuclear imaging plays a prominent role in detecting these subclinical effects, which could potentially serve as predictors of late cardiac complications. Discussion: However, further studies with larger populations, longer follow-up periods, and specific heart dosimetric data are needed to better understand the relationship between early detection of cardiac abnormalities and radiation-induced heart disease.

Repeated Stereotactic Radiotherapy for Local Brain Metastases Failure or Distant Brain Recurrent: A Retrospective Study of 184 Patients.

BACKGROUND: The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. METHODS: we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. RESULTS: In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7-10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). CONCLUSIONS: Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.

Prognostic Factors in Extremity Soft Tissue Sarcomas Treated with Radiotherapy: Systematic Review of the Literature.

Soft tissue sarcomas of the extremities are rare tumors with various prognostic factors. Their management is debatable due to their inconsistent results within the literature and the lack of large prospective studies. The objective of this systematic review is to analyze the available scientific data on prognostic factors concerning the characteristics of the patients, the disease and the treatments performed, as well as their potential complications, on studies with a median follow-up of 5 years at minimum. A search of articles following the "PRISMA method" and using the PubMed search engine was conducted to select the most relevant studies. Twenty-five articles were selected, according to preestablished criteria. This review provides a better understanding of the prognosis and disease outcome of these tumors. Many factors were described comparing the frequency of occurrence according to the studies, which remain heterogeneous between them. Significant factors that could orient patients to radiotherapy were highlighted. These positive prognostic factors provide valuable insight to optimize radiotherapy treatments for patients treated for soft tissue sarcoma of the extremities.

Stereotactic Radiation Therapy of Single Brain Metastases: A Literature Review of Dosimetric Studies.

Stereotactic radiotherapy (SRT) plays a major role in treating brain metastases (BMs) and can be delivered using various equipment and techniques. This review aims to identify the dosimetric factors of each technique to determine whether one should be preferred over another for single BMs treatment. A systematic literature review on articles published between January 2015 and January 2022 was conducted using the MEDLINE and ScienceDirect databases, following the PRISMA methodology, using the keywords "dosimetric comparison" and "brain metastases". The included articles compared two or more SRT techniques for treating single BM and considered at least two parameters among: conformity (CI), homogeneity (HI) and gradient (GI) indexes, delivery treatment time, and dose-volume of normal brain tissue. Eleven studies were analyzed. The heterogeneous lesions along with the different definitions of dosimetric indexes rendered the studied comparison almost unattainable. Gamma Knife (GK) and volumetric modulated arc therapy (VMAT) provide better CI and GI and ensure the sparing of healthy tissue. To conclude, it is crucial to optimize dosimetric indexes to minimize radiation exposure to healthy tissue, particularly in cases of reirradiation. Consequently, there is a need for future well-designed studies to establish guidelines for selecting the appropriate SRT technique based on the treated BMs' characteristics.

Evaluation of Cardiac Substructures Exposure of DIBH-3DCRT, FB-HT, and FB-3DCRT in Hypofractionated Radiotherapy for Left-Sided Breast Cancer after Breast-Conserving Surgery: An In Silico Planning Study.

Left-sided breast cancer radiotherapy can lead to late cardiovascular complications, including ischemic events. To mitigate these risks, cardiac-sparing techniques such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed. However, recent studies have shown that mean heart dose is not a sufficient dosimetric parameter for assessing cardiac exposure. In this study, we aimed to compare the radiation exposure to cardiac substructures for ten patients who underwent hypofractionated radiotherapy using DIBH three-dimensional conformal radiation therapy (3DCRT), free-breathing (FB)-3DCRT, and FB helical tomotherapy (HT). Dosimetric parameters of cardiac substructures were analyzed, and the results were statistically compared using the Wilcoxon signed-rank test. This study found a significant reduction in the dose to the heart, left anterior descending coronary artery, and ventricles with DIBH-3DCRT and FB-HT compared to FB-3DCRT. While DIBH-3DCRT was very effective in sparing the heart, in some cases, it provided little or no cardiac sparing. FB-HT can be an interesting treatment modality to reduce the dose to major coronary vessels and ventricles and may be of interest for patients with cardiovascular risks who do not benefit from or cannot perform DIBH. These findings highlight the importance of cardiac-sparing techniques for precise delivery of radiation therapy.

Efficacity of Deep Inspiration Breath Hold and Intensity-Modulated Radiotherapy in Preventing Perfusion Defect for Left Sided Breast Cancer (EDIPE): A Prospective Cohort Study Protocol.

Breast radiotherapy can lead to radiation-induced cardiac disease, particularly in left breast cancers. Recent studies have shown that subclinical cardiac lesions, such as myocardial perfusion deficits, may occur early after radiotherapy. The primary method for irradiating breast cancer, known as opposite tangential field radiotherapy, can cause the anterior interventricular coronary artery to receive a high dose of radiation during left breast irradiation. To explore alternative approaches that could reduce the risk of myocardial perfusion defects in patients with left breast cancer, we plan to conduct a prospective single-center study using a combination of deep inspiration breath hold radiotherapy and intensity modulated radiation therapy. The study will use stress and, if necessary, resting myocardial scintigraphy to assess myocardial perfusion. The trial aims to show that reducing the cardiac dose with these techniques can prevent the appearance of early (3-month) and medium-term (6- and 12-month) perfusion disorders.

Outcome of lung oligometastatic patients treated with stereotactic body irradiation.

Purpose: The oligometastatic stage is an intermediate stage of cancer between the localized stage and polymetastatic stage. The prognosis of patients in this stage also appears to be intermediate. Lung stereotactic body radiotherapy is a possible tool for treating oligometastatic lung sites. The objective of our study was to evaluate the clinical outcomes in terms of local control, progression-free survival, overall survival, and toxicity of SBRT in oligometastatic patients with lung metastases from any solid primary tumor. Materials and methods: Clinical records of consecutive lung oligometastatic patients treated between January 2010 and December 2020 for lung SBRT at 60 Gy in 3- or 8-fraction schedules and a controlled primary tumor were retrospectively analyzed. Results: After a median follow-up of 20.3 months, local failure occurred for 14 lesions, 57 patients experienced lung progression, and 64 patients experienced disease progression. Overall survival rates at 1 and 2 years were 85.6 and 69.7%, respectively. Fifty-two patients experienced radiation pneumonitis, but only 2 patients were symptomatic and presented grade 2 late pneumonitis. No grade 3-4 toxicity was observed. ECOG 0 was the only prognostic factor for overall survival (HR = 3.5; 95% CI 3.2-3.8; p < 0.01). Conclusion: SBRT with a 60-Gy schedule in 8 fractions is an effective and well-tolerated treatment for patients with lung oligometastases from any solid primary tumor.

Ellipsoid calculations versus manual tumor delineations for glioblastoma tumor volume evaluation.

In glioblastoma, the response to treatment assessment is essentially based on the 2D tumor size evolution but remains disputable. Volumetric approaches were evaluated for a more accurate estimation of tumor size. This study included 57 patients and compared two volume measurement methods to determine the size of different glioblastoma regions of interest: the contrast-enhancing area, the necrotic area, the gross target volume and the volume of the edema area. The two methods, the ellipsoid formula (the calculated method) and the manual delineation (the measured method) showed a high correlation to determine glioblastoma volume and a high agreement to classify patients assessment response to treatment according to RANO criteria. This study revealed that calculated and measured methods could be used in clinical practice to estimate glioblastoma volume size and to evaluate tumor size evolution.

Local recurrence and cerebral progression-free survival after multiple sessions of stereotactic radiotherapy of brain metastases: a retrospective study of 184 patients : Statistical analysis.

PURPOSE: Forty to sixty percent of patients treated with focal therapy for brain metastasis (BM) will have distant brain recurrence (C-LR), while 10-25% of patients will have local recurrence (LR) within 1 year after stereotactic radiotherapy (SRT). The purpose of this study was to analyze cerebral progression-free survival (C-PFS) and LR of BM among patients treated with repeated courses of radiotherapy in stereotactic conditions. METHODS AND MATERIALS: We retrospectively reviewed data from 184 patients treated for 915 BMs with at least two courses of SRT without previous WBRT. Initial patient characteristics, patient characteristics at each SRT, brain metastasis velocity (BMV), delay between SRT, MRI response, LR and C­LR were analyzed. RESULTS: In all, 123 (66.9%), 39 (21.2%), and 22 (12%) patients received 2, 3, or 4 or more SRT sessions, respectively. Ninety percent of BMs were irradiated without prior surgery, and 10% were irradiated after neurosurgery. The MRI response at 3, 6, 12 and 24 months after SRT was stable regardless of the SRT session. At 6, 12 and 24 months, the rates of local control were 96.3, 90.1, and 85.8%, respectively. In multivariate analysis, P­LR was statistically associated with kidney (HR = 0.08) and lung cancer (HR = 0.3), ECOG 1 (HR = 0.5), and high BMV grade (HR = 5.6). The median C­PFS after SRT1, SRT2, SRT3 and SRT4 and more were 6.6, 5.1, 6.7, and 7.7 months, respectively. C­PFS after SRT2 was significantly longer among patients in good general condition (HR = 0.39), patients with high KPS (HR = 0.91), patients with no extracerebral progression (HR = 1.8), and patients with a low BMV grade (low vs. high: HR = 3.8). CONCLUSION: Objective MRI response rate after repeated SRT is stable from session to session. Patients who survive longer, such as patients with breast cancer or with low BMV grade, are at risk of local reirradiation. C­PFS after SRT2 is better in patients in good general condition, without extracerebral progression and with low BMV grade.

Stereotactic Body Radiotherapy for Patients with Lung Oligometastatic Disease: A Five-Year Systematic Review.

For several years, oligometastatic disease has represented an intermediate state between localized disease accessible to local treatment and multimetastatic disease requiring systemic therapy. The lung represents one of the most common metastatic locations. Stereotactic body radiation therapy (SBRT) appears to be the treatment of choice for these patients. There are few data defining the place of radiotherapy and reporting outcome after SBRT in lung metastases. This 5-year review aimed to determine areas of SBRT usefulness and methods for the management of pulmonary metastasis in oligometastatic patients. A search for articles on PubMed allowed selection of the most relevant studies. Eighteen articles were selected according to pre-established criteria for this purpose. The analysis concludes that SBRT is an effective and safe treatment in selected patients when the disease remains localized from one to three organs.

Role of hippocampal location and radiation dose in glioblastoma patients with hippocampal atrophy.

BACKGROUND: The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. METHODS: All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy. RESULTS: Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. CONCLUSIONS: There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

Pseudoprogression versus true progression in glioblastoma patients: A multiapproach literature review. Part 2 - Radiological features and metric markers.

After chemoradiotherapy for glioblastoma, pseudoprogression can occur and must be distinguished from true progression to correctly manage glioblastoma treatment and follow-up. Conventional treatment response assessment is evaluated via conventional MRI (contrast-enhanced T1-weighted and T2/FLAIR), which is unreliable. The emergence of advanced MRI techniques, MR spectroscopy, and PET tracers has improved pseudoprogression diagnostic accuracy. This review presents a literature review of the different imaging techniques and potential imaging biomarkers to differentiate pseudoprogression from true progression.

Pseudoprogression versus true progression in glioblastoma patients: A multiapproach literature review: Part 1 - Molecular, morphological and clinical features.

With new therapeutic protocols, more patients treated for glioblastoma have experienced a suspicious radiologic image of progression (pseudoprogression) during follow-up. Pseudoprogression should be differentiated from true progression because the disease management is completely different. In the case of pseudoprogression, the follow-up continues, and the patient is considered stable. In the case of true progression, a treatment adjustment is necessary. Presently, a pseudoprogression diagnosis certainly needs to be pathologically confirmed. Some important efforts in the radiological, histopathological, and genomic fields have been made to differentiate pseudoprogression from true progression, and the assessment of response criteria exists but remains limited. The aim of this paper is to highlight clinical and pathological markers to differentiate pseudoprogression from true progression through a literature review.

Effects of a metallic implant on radiotherapy planning treatment-experience on a human cadaver.

BACKGROUND: Metallic implants (MIs) complicate radiotherapy planning. Several studies have worked on tissue-equivalent phantoms as experimental models to estimate dose distributions in this context. The application of these results to clinical practice remains disputable because the inhomogeneity of human tissue densities is a difficult factor to integrate into dose calculation software. In this work, we evaluate the impact of human tissue inhomogeneities by assessing the discrepancies between treatment planning system (TPS) dose calculations and measured delivered doses on a human cadaver with hip prostheses. METHODS: A total of 143 alanine dosimeters were positioned in contact with the prostheses (bones group), soft tissues (soft tissues group), skin surfaces (skin group) and natural cavities (cavities group) of a human cadaver. The planning target volume (PTV) corresponded to a standard endometrial cancer treatment. The irradiation was performed with 6 MV X-ray tomotherapy at the one fraction-dose of 10 Gy. RESULTS: A total of 140 dosimeters were analyzed. After applying a temperature correction coefficient to the measured doses, the global analysis of all dosimeters showed a significant difference between the calculated doses and the measured doses (P<0.001). For dosimeters of the bones, soft tissues, skin and cavities groups, this difference was also significant (P<0.001 for each group). The mean measured doses were 21.9% lower than the mean calculated doses in the global analysis and 17.0%, 21.2%, 33.0% and 19.0% lower for the bones, soft tissues, skin and cavities groups, respectively. CONCLUSIONS: This study showed that the received doses were significantly lower than the calculated doses and suggested the need to improve the understanding of this discrepancy.

18F-FDOPA PET/CT Combined with MRI for Gross Tumor Volume Delineation in Patients with Skull Base Paraganglioma.

In this simulation study, we assessed differences in gross tumor volume (GTV) in a series of skull base paragangliomas (SBPGLs) using magnetic resonance imaging (MRI), 18F-dihydroxyphenylalanine (18F-FDOPA) combined positron emission tomography/computed tomography (PET/CT), and 18F-FDOPA PET/MRI images obtained by rigid alignment of PET and MRI. GTV was delineated in 16 patients with SBPGLs on MRI (GTVMRI), 18F-FDOPA PET/CT (GTVPET), and combined PET/MRI (GTVPET/MRI). GTVPET/MRI was the union of GTVMRI and GTVPET after visual adjustment. Three observers delineated GTVMRI and GTVPET/MRI independently. Excellent interobserver reproducibility was found for both GTVMRI and GTVPET/MRI. GTVPET and GTVMRI were not significantly different. However, there was some spatial difference between the locations of GTVMRI, GTVPET, and GTVPET/MRI. The Dice similarity coefficient median value was 0.4 between PET/CT and MRI, and 0.8 between MRI and PET/MRI. The combined use of PET/MRI produced a larger GTV than MRI alone. Nevertheless, both the target-delivered dose and organs-at-risk conservancy were respected when treatment was planned on the PET/MRI-matched data set. Future integration of 18F-FDOPA PET/CT into clinical practice will be necessary to evaluate the influence of this diagnostic modality on SBPGL therapeutic management. If the clinical utility of 18F-FDOPA PET/CT and/or PET/MRI is confirmed, GTVPET/MRI should be considered for tailored radiotherapy planning in patients with SBPGL.

A systematic review of palliative bone radiotherapy based on pain relief and retreatment rates.

Palliative radiotherapy has been shown to have effects on Quality of Life during painful bone metastasis. This review aimed to determine equivalence in pain relief (PR) and retreatment rate (RR) using both single and multi-fraction irradiations, based on evaluation of the trial's quality. We performed a systematic review since ICRU 50 Report (1993) to June 2017, then evaluated trials for reproducibility and good methodology criteria. We found five studies that were reproducible in both dose and volume prescription. One study used three-dimensional (3D) treatment planning. Equivalence between single and multi-fraction schedules was demonstrated for PR after 3 months, but a 2-3 time RR appeared after single-fraction schedules, notably in the first year after treatment (primarily during the first four months). Reserving long course therapy for well-preserved patients would allow for better long-term efficacy with lower RR, while altered patients would suffer less from single-fraction treatments. It appears that life expectancy might not be used as a criterion for this choice.