Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection.

INTRODUCTION: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). MATERIALS AND METHODS: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. RESULTS: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). CONCLUSION: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.

Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review.

BACKGROUND: Definitive external beam radiotherapy (EBRT) is an unusual treatment of unresectable soft-tissue sarcomas (STS). Recent technical innovations and physical advantages of particle therapies may improve results of this therapeutic option. The role of this review was to report the clinical results of photon- and particle-based EBRT in unresectable STS. MATERIAL AND METHODS: We performed a systematic review of the literature on Pubmed database to identify studies investigating the efficacy and safety of EBRT. The primary endpoint was local control (LC) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events in a subset of patients with gross disease STS. RESULTS: We identified 29 studies involving 1409 patients (pts) evaluating photon (n = 18; 956 pts), proton (n = 1; 21 pts), carbon ion (n = 2; 152 pts), neutron (n = 7; 259 pts) or pion (n = 1; 21 pts) therapy. Definitive EBRT achieves valuable 5-year LC rates of 28-73% with photon and 52-69% with particle therapies. Most local failures (66-100%) occurred within 3 years. Long-term disease control can be achieved in a fraction of patients, with 5-year PFS and OS of 0-39% and 24.7-63%, respectively. The rate of severe adverse events was highly variable with photons, <15% in proton and carbon ion therapy, whereas 25 to 50% of patients treated with neutrons and pions presented severe AE. While a dose higher or equal 64 Gy seem to improve the prognosis, delivering a dose higher or equal 68 Gy dramatically increases severe adverse events. CONCLUSION: Definitive EBRT with dose 64-66 Gy seems to be a safe and efficient treatment for unresectable STS. Future clinical trials should assess the potential of biomarkers of response, thus identifying patients that could benefit from local treatment.

Gemcitabine-Based Chemoradiotherapy Enhanced by a PARP Inhibitor in Pancreatic Cancer Cell Lines.

Pancreatic ductal adenocarcinoma is a devastating disease with a 5-year overall survival of 9% for all stages. Gemcitabine-based chemoradiotherapy for locally advanced pancreatic cancer is highly toxic. We conducted an in vitro study to determine whether poly(ADP-ribose) polymerase-1 inhibition radiosensitized gemcitabine-based chemotherapy. Human pancreatic cancer cell lines, MIA PaCa-2, AsPC-1, BxPC-3 and PANC-1 were treated with gemcitabine (10 nM) and/or olaparib (1 µM). Low-LET gamma single dose of 2, 5 and 10 Gy radiations were carried out. Clonogenic assay, PAR immunoblotting, cell cycle distribution, γH2Ax, necrotic and autophagic cell death quantifications were performed. Treatment with olaparib alone was not cytotoxic, but highly radiosensitized cell lines, particularly at high dose per fraction A non-cytotoxic concentration of gemcitabine radiosensitized cells, but less than olaparib. Interestingly, olaparib significantly enhanced gemcitabine-based radiosensitization in PDAC cell lines with synergistic effect in BxPC-3 cell line. All cell lines were radiosensitized by the combination of gemcitabine and olaparib, through an increase of unrepaired double-strand, a G2 phase block and cell death. Radiosensitization was increased with high dose of radiation. The combination of olaparib with gemcitabine-based chemoradiotherapy could lead to an enhancement of local control in vivo and an improvement in disease-free survival.

Surgery Is an Effective Option after Failure of Chemoradiation in Cancers of the Anal Canal and Anal Margin.

BACKGROUND: Surgery for anal canal cancer (ACC) and anal margin cancer (AMC) is the only curative option after failure of chemoradiotherapy (CRT). This study aimed to determine the efficacy of surgery for ACC or AMC after failed CRT. METHODS: This was a single-centre, retrospective study of 161 patients initially treated with CRT. We compared the survival rates of patients successfully treated by CRT with those of patients whose CRT failed (both surgically salvaged and treated palliatively). RESULTS: Thirty-one patients underwent surgery with curative intent, 20 received palliative treatment after failure of CRT, and 110 had effective CRT. The 5-year overall survival (OS) rate was significantly higher among patients with successful CRT than among patients who underwent surgery with curative intent (86 vs. 66%, p < 0.001). On the other hand, the 5-year OS of patients treated with curative surgery was significantly better than that of patients who underwent palliative treatment (66 vs. 13.5%, p < 0.001). The postoperative morbidity and mortality rates were 32 and 3%, respectively. Considering patients with failed CRT, curative surgery was the only factor prognostic of favourable OS in the multivariate analysis. CONCLUSION: Curative surgery after failure of CRT for ACC or AMC remains an effective treatment to improve survival in two-thirds of cases, resulting in high but manageable morbidity.

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.

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.

Optimizing lung cancer radiation therapy: A systematic review of multifactorial risk assessment for radiation-induced lung toxicity.

BACKGROUND: Radiation therapy (RT) is essential in treating advanced lung cancer, but may lead to radiation pneumonitis (RP). This systematic review investigates the use of pulmonary function tests (PFT) and other parameters to predict and mitigate RP, thereby improving RT planning. METHODS: A systematic review sifted through PubMed and on BioMed Central, targeting articles from September 2005 to December 2022 containing the keywords: Lung Cancer, Radiotherapy, and pulmonary function test. RESULTS: From 1153 articles, 80 were included. RP was assessed using CTCAEv.4 in 30 % of these. Six studies evaluated post-RT quality of life in lung cancer patients, reporting no decline. Patients with RP and chronic obstructive pulmonary disease (COPD) generally exhibited poorer overall survival. Notably, forced expiratory volume in one second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) declined 24 months post-RT, while forced vital capacity (FVC) stayed stable. In the majority of studies, age over 60, tumors located in the lower part of the lung, and low FEV1 before RT were associated with a higher risk of RP. Dosimetric factors (V5, V20, MLD) and metabolic imaging emerged as significant predictors of RP risk. A clinical checklist blending patient and tumor characteristics, PFT results, and dosimetric criteria was proposed for assessing RP risk before RT. CONCLUSION: The review reveals the multifactorial nature of RP development following RT in lung cancer. This approach should guide individualized management and calls for a prospective study to validate these findings and enhance RP prevention strategies.

Stereotactic body radiation therapy in unresectable stage III non-small cell lung cancer: A systematic review.

In unresectable stage III non-small cell lung cancer (NSCLC), the standard of care for most fit patients is concurrent chemotherapy with normofractionated radiotherapy (NFRT), followed by durvalumab consolidation. Nevertheless, almost half of patients will present locoregional or metastatic intrathoracic relapse. Improving locoregional control thus remains an important objective. For this purpose, stereotactic body radiotherapy (SBRT) may be a relevant treatment modality. We performed a systematic review of the literature that evaluate the efficacy and safety of SBRT in this situation, either instead of or in addition to NFRT. Among 1788 unique reports, 18 met the inclusion criteria. They included 447 patients and were mainly prospective (n = 10, including 5 phase 2 trials). In none, maintenance durvalumab was administered. Most reported SBRT boost after NFRT (n = 8), or definitive tumor and nodal SBRT (n = 7). Median OS varied from 10 to 52 months, due to the heterogeneity of the included populations and according to treatment regimen. The rate of severe side effects was low, with <5 % grade 5 toxicity, and mainly observed when mediastinal SBRT was performed without dose constraints to the proximal bronchovascular tree. It was suggested that a biologically effective dose higher than 112.3 Gy may increase locoregional control. SBRT for selected stage III NSCLC bears potential to improve loco-regional tumor control, but at present, this should only be done in prospective clinical trials.

Immunotherapy for Soft Tissue Sarcomas: Anti-PD1/PDL1 and Beyond.

Sarcomas gather a heterogeneous group of mesenchymal malignant tumors including more than 150 different subtypes. Most of them represent aggressive tumors with poor prognosis at the advanced stage, despite the better molecular characterization of these tumors and the development of molecular-driven therapeutic strategies. During the last decade, immunotherapy has been developed to treat advanced cancers, mainly thanks to immune checkpoint inhibitors (ICI) such as anti-PD1/PDL1 and later to adoptive immune cell therapies. In this review, we aim to summarize the state of the art of immunotherapy in soft tissue sarcomas (STS). Overall, the clinical trials of ICI that included a wide diversity of STS subtypes reported limited efficacy with some outlying responders. Both emerging biomarkers are of interest in selecting good candidates and in the development of combination therapies. Finally, the recent breakthroughs of innovative adoptive therapies in STS seem highly promising.

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.

Long-term outcomes after definitive radiotherapy with modern techniques for unresectable soft tissue sarcoma.

INTRODUCTION: The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option. METHODS: We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p < 0.001). Macroscopically incomplete resection and EQD2 ≥ 64 Gy were associated with better OS (p = 0.016 and p = 0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients. CONCLUSION: In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.

Radiosensitizing Pancreatic Cancer with PARP Inhibitor and Gemcitabine: An In Vivo and a Whole-Transcriptome Analysis after Proton or Photon Irradiation.

Over the past few years, studies have focused on the development of targeted radiosensitizers such as poly(ADP-ribose) polymerase inhibitors. We performed an in vivo study and a whole-transcriptome analysis to determine whether PARP inhibition enhanced gemcitabine-based chemoradiosensitization of pancreatic cancer xenografts, combined with either proton or photon irradiation. NMRI mice bearing MIA PaCa-2 xenografts were treated with olaparib and/or gemcitabine and irradiated with 10 Gy photon or proton. First, a significant growth inhibition was obtained after 10 Gy proton irradiation compared to 10 Gy photon irradiation (p = 0.046). Moreover, the combination of olaparib, gemcitabine and proton therapy significantly sensitized tumor xenografts, compared to gemcitabine (p = 0.05), olaparib (p = 0.034) or proton therapy (p < 0.0001) alone or to the association of olaparib, gemcitabine and radiotherapy (p = 0.024). Simultaneously, whole RNA sequencing profiling showed differentially expressed genes implicated in categories such as DNA repair, type I interferon signaling and cell cycle. Moreover, a large amount of lncRNA was dysregulated after proton therapy, gemcitabine and olaparib. This is the first study showing that addition of olaparib to gemcitabine-based chemoradiotherapy improved significantly local control in vivo, especially after proton therapy. RNA sequencing profiling analysis presented dynamic alteration of transcriptome after chemoradiation and identified a classifier of gemcitabine response.

Impact of histological subtype on radiological and pathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: Evaluation of response to neoadjuvant radiotherapy (NART) does not consider soft tissue sarcoma (STS) heterogeneity. We aimed to investigate radiological and pathological response of 4 major histotypes. METHODS: Extremity or trunk STS patients who received 50 Gy NART between 2009 and 2020 were retrospectively included. Relative variation in tumor size (RVTS) and pathological response were reported in the overall population and in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), myxoid liposarcoma (MLS) and synovial sarcoma (SS) patients to identify response modalities of each histotype. RESULTS: Among the 121 included patients, 49, 19, 13 and 11 presented UPS, MFS, MLS and SS. Median RVTS were 0% (IQR -18-+18), +8% (IQR 0-+24), -12% (IQR -20-3) and -11% (IQR -15-9), respectively (p = 0.001). Median viable cells were 10%, 60%, 20% and 70% (p = 0.007). In overall population, pathological complete response and median necrosis were 27.7% and 10% without significant correlation to histotype (p = 0.18 and 0.06). Nineteen (38.8%) UPS specimens presented cysts that were emptied during the sampling process and distorted the microscopic response evaluation. Infiltrative growth pattern was observed in 28% and 38.9% UPS and MFS patients. Five (38.5%) MLS presented mature adipocytes without proven prognostic value. Cysts were observed in 36% of SS specimens. In the absence of initial tumor limits, the great viable cellularity of SS may be overestimated by their nodular aspect. CONCLUSION: After NART, we highlighted disparate response of UPS, frequent progression of MFS, and confirmed MLS and SS radiosensitivity. Response must be interpreted with caution and consider the histotype-specific patterns.

Targeting DNA repair in combination with radiotherapy in pancreatic cancer: A systematic review of preclinical studies.

BACKGROUND: Current research that combines radiation with targeted therapy may dramatically improve prognosis of pancreatic ductal adenocarcinoma (PDAC). We investigated preclinical outcomes of DNA repair inhibitor targeted therapy associated with radiotherapy. METHODS: We searched Pubmed database to identify publications assessing DNA damage targeted therapies in preclinical models of PDACin vitro and in vivo. Standard enhancement ratio, median survival and growth delay were extracted. RESULTS: We identified fourteen publications using DNA repair targeted therapies in preclinical models of PDAC. Ten publications comprising twenty-eight experiments evaluated radiosensitization with different DNA repair inhibitors in vitro and displayed cell killing by a factor of 1.35 ±â€¯0.047. Moreover, 86 % (24/28) of in vitro experiments showed radiosensitization with DNA damage response inhibitor. However, only 60 % (9/15) of the in vivo experiments presented radiosensitization effects. CONCLUSION: DNA repair targeted therapies use promising radiosensitizers for PDAC and could successfully be translated into clinical trials.

A critical narrative review of radiotherapy for retroperitoneal soft tissue sarcoma.

Retroperitoneal sarcomas (RPSs) are rare diseases, and the 5-year overall survival rate remains low. Management of RPSs is challenging, and the quality of treatment strategy is a crucial prognostic factor. Treatment decisions and the treatment department to which the patients is referred must be centralized. Overall survival rate is positively correlated with the number of patients treated in the centers. En bloc surgery is the standard of care for effective treatment and potential for cure, whereas perioperative chemotherapy or radiotherapy has not yet been validated. Pre- or postoperative radiotherapy was considered controversial, but the STRASS trial publication illustrated that preoperative radiation could be useful in some conditions. Retroperitoneal liposarcoma might become a future target of prospective trials. Furthermore, some retrospective studies have shown that preoperative radiotherapy increases the rate of R0-R1 resections. This article reviews the role of external beam radiotherapy in the management of RPS and highlights the optimal volumes, doses, and radiotherapy techniques for the treatment of RPS. As accurately predicting prognosis in patients with RPS is challenging, we also emphasize the utility of nomograms in the field of radiotherapy. However, these nomograms do not include radiotherapy as a predictive factor. Although some authors could conclude that use of radiotherapy should be avoided based on the results of the STRASS trial, some data argue that radiotherapy still has utility in select cases.

Total body irradiation in allogeneic bone marrow transplantation conditioning regimens: A review.

Hematologic malignancies may require, at one point during their treatment, allogeneic bone marrow transplantation. Total body irradiation combined with chemotherapy or radiomimetic used in allogeneic bone marrow transplantation is known to be very toxic. Total body irradiation (TBI) induces immunosuppression to prevent the rejection of donor marrow. TBI is also used to eradicate malignant cells and is in sanctuary organs that are not reached by chemotherapy drugs. TBI has evolved since its introduction in the late fifties, but acute and late toxicities remain. Helical tomotherapy, which is widely used for some solid tumors, is a path for the improvement of outcomes and toxicities in TBI because of its sparing capacities. In this article, we first review the practical aspects of TBI with patient positioning, radiobiological considerations and total dose and fractionation prescriptions. Second, we review the use of intensity modulated radiation therapy in bone marrow transplantation with a focus on helical tomotherapy TBI, helical tomotherapy total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) and their dosimetric and clinical outcomes. Finally, we review the perspective of dose escalation and the extension to older patients and patients with comorbidity who do not benefit from a standard bone marrow transplantation conditioning regimen.

Poly-(ADP-ribose)-polymerase inhibitors as radiosensitizers: a systematic review of pre-clinical and clinical human studies.

BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality. Furthermore the replication-dependent activity of PARP inhibitor helps to maintain the differential effect between tumoral and healthy tissues. Inhibition of chromatin remodeling, G2/M arrest, vasodilatory effect induced by PARP inhibitor, also participate to their radio-sensitization effect. MATERIALS AND METHODS: Here, after highlighting mechanisms of PARP inhibitors radiosensitization we methodically searched PubMed, Google Scholar, Cochrane Databases and meeting proceedings for human pre-clinical and clinical studies that evaluated PARP inhibitor radiosensitizing effect. Enhancement ratio, when available, was systematically reported. RESULTS: Sixty four studies finally met our selection criteria and were included in the analysis. Only three pre-clinical studies didn't find any radiosensitizing effect. Median enhancement ratio vary from 1,3 for prostate tumors to 1,5 for lung cancers. Nine phase I or II trials assessed safety data. CONCLUSION: PARP inhibitors are promising radiosensitizers, but need more clinical investigation. The next ten years will be determining for judging their real potential.

Is the lack of respiratory gating prejudicial for left breast TomoDirect treatments?

BACKGROUND AND PURPOSE: TomoDirect (TD) can only operate in free-breathing. The purpose of this study is to compare TD with breath-hold 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) techniques for left breast treatments, and to determine if the lack of respiratory gating is a handicap for cardiac sparing. MATERIALS AND METHODS: 15 patients treated for left breast had two computed tomography simulation, in free breathing (FB) and in deep-inspiration breath-hold (DIBH). Four treatments were planned: TD-FB, 3DCRT-FB, 3DCRT-DIBH and IMRT-DIBH. Dose to PTV, heart, lungs, right breast and patient were compared. RESULTS: A slightly lower cardiac mean dose is found for 3DCRT-DIBH than for TD-FB group (1.99Gy Vs 2.89Gy, p=0.0462), while no statistical difference is found for heart V20. TD-FB plans show the best PTV dose homogeneity (0.053, p<0.001) and the lowest left lung mean dose (5.16Gy, p<0.001). No major differences are found for the other organs. CONCLUSIONS: TomoDirect and breath-hold 3DCRT are complementary techniques for left breast treatments: for a minority of patients, respiratory gating is mandatory to lower cardiac dose; for the remaining majority of patients, TomoDirect achieves better PTV homogeneity and reduced left lung dose, with cardiac dose equivalent to 3DCRT-DIBH.