Cardiac substructures exposure in left-sided breast cancer radiotherapy: Is the mean heart dose a reliable predictor of cardiac toxicity?

PurposeThis study aimed to assess radiation dose distribution to cardiac subvolumes in left-sided breast cancer radiotherapy (LBCRT) and to clarify whether the mean heart dose (MHD) reliably reflects cardiac substructures exposure.Materials and methodsFifty women referred for adjuvant LBCRT were prospectively evaluated. All patients received 3D-conformal hypofractionated radiotherapy (40 Gy delivered in 15 fractions of 2.67 Gy ± boost of 13.35 Gy). Cardiac substructures were contoured using the F. Duane's cardiac atlas. Dose distribution to cardiac chambers, left main (LM), left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA)) was assessed. Dosimetric associations were analysed.ResultsThe mean MHD was 3.08 Gy (EQD2 = 3.67 Gy). The mean Dmean/Dmax LAD was 11.45 Gy (EQD2 = 13.64 Gy)/29.5 Gy (EQD2 = 35.15 Gy). Low doses were delivered to LM, LCx, and RCA (Dmean ≤ 1.3 Gy). The left ventricle (LV) was the most exposed cardiac chamber with Dmean/Dmax of 4.78 Gy/37 Gy. The strongest correlation with MHD was found for Dmean LAD (r = 0.81). For every 1 Gy increase in MHD, Dmean LAD rose by 3.4 Gy. However, the proportion of variance in Dmean LAD predictable from MHD was moderate (R² = 0.65). For all other cardiac substructures, R² values were < 0.7.ConclusionOur study showed high exposure of LAD and LV in LBCRT. With poor predictive value, MHD may underestimate doses to cardiac substructures. For optimal heart sparing radiotherapy, we recommend to consider LV and LAD as separate organ at risk.     

Dosimetric comparison of four high performance techniques for irradiation of breast cancer patients

PurposeThe use of IMRT for the treatment of breast cancer has been growing considerably in our institution since 2009. Alternatively, helical tomotherapy (HT) using a field width of 2.5 and 5 cm (HT_FW_5), volumetric-modulated arc therapy (VMAT), or proton therapy with pencil-beam scanning (PT-PBS) have also been used to reduce treatment duration or optimize organ-at-risk (OAR) sparing. The purpose of this study was to compare the 4 treatment modalities available at our site.Patients and methodsWe studied 10 patients treated for breast cancer with lymph node involvement. The prescribed dose was 51.8 Gy to the breast with a simultaneous integrated boost up to 63 Gy, and 50.4 Gy to lymph nodes in 28 fractions. The CTV was delineated according to ESTRO Guidelines. Dosimetric planning in routine clinical practice was performed using HT_FW_2.5. The approved clinical plan was compared to the 3 other plans. Dosimetric goals for PTV coverage were D95% ≥ 95% and D2% ≤ 107% of the prescribed dose. Mean and maximum doses to OAR were recorded.ResultsHT_FW_5 and VMAT plans ensure equivalent or even better PTV coverage compared to the initial clinically approved plan but at the cost of poorer OAR sparing. PT_PBS plans showed that an excellent PTV coverage can be maintained with significantly lower doses to OAR.ConclusionHT_FW_5 and VMAT plans allow a significant reduction of treatment duration and can be a good alternative to HT_FW_2.5 for specific populations. HT_FW_2.5 could be chosen for patients at higher risk of side effects. In addition, PT_PBS should be considered in the near future as it has been shown to have a major potential benefit to lower the risk of side effects with the same level of PTV coverage.     

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PurposeDeep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI).Materials and methodsThis retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient.ResultsMean heart dose was 7.9 Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint < 8 Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (r_s = –0.25, P = 0.050) and between mean heart dose and CCDps (r_s = 0.25, P = 0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant.ConclusionOur dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.     

Techniques classique bidimensionnelle et mono-isocentrique tridimensionnelle dans l’irradiation du sein et des aires ganglionnaires : comparaison dosimétrique

PurposeThe activity of our radiation oncology department mainly relies on breast pathology. Since July 2009, all the irradiations delivered simultaneously to the breast (CTV1), the surgical bed (CTV2), the internal mammary chain and the supra- and infraclavicular areas have been carried out using a mono-isocentric technique. This study aimed to compare dosimetric results between conventional 2D and mono-isocentric 3D techniques with or without optimization.Patients and methodsFrom January to August 2009, 20 patients with breast cancer in whom irradiation of the CTV1, CTV2, internal mammary chain and supra- and infraclavicular areas was retained, were included in a specific cohort. In each case, we have compared dosimetric results obtained with the conventional technique and with a mono-isocentric 3D technique, either with manual field in the field segmentation or with automatic segmentation (Oncentra Masterplan^® from Nucletron^®, Optimizer^® solution). Selected criteria were as follows: V95, V107 and mean dose (Dmean) to the target volumes, V20 and V30 to the ipsilateral lung, V35 and mean dose to the heart and maximal dose (Dmax) to the spinal cord.ResultsSupra- and infraclavicular areas irradiation was significantly better using the mono-isocentric 3D technique (V95 %: 89.7 % vs. 77.1 %; P = 0.001) as well as dose homogeneity (Dmean: 46.3 Gy vs. 45.1 Gy; P = 0.008). No statistical difference was observed for the other target volumes. Heart and spinal cord protection were better with the mono-isocentric 3D technique (respectively Dmean: 8.4 Gy vs. 11.1 Gy; P < 0.0001 and Dmax: 29.2 Gy vs. 35.8 Gy; P = 0.0003).ConclusionMono-isocentric irradiation of the breast and lymphatic areas is a modern technique that benefits from imaging and computer progresses while being simple to carry out using standard planning system and linear accelerators. Mono-isocentric 3D irradiation with manual segmentation of the breast and the nodal areas provides a target volume irradiation comparing with conventional technique 2D and a better protection of the heart and of the spinal cord.     

Five-fraction HDR brachytherapy in locally advanced cervical cancer: A monocentric experience

PurposeThe 5-fraction scheme (5 × 5–5.5 Gy) is a common High-Dose Rate (HDR) intracavitary brachytherapy regimen for locally advanced cervical cancer (LACC). Yet, its equivalence with Pulse-Dose rate (PDR) schemes remains unproved. The present study aimed at reporting on the outcome of LACC patients treated with 5-fraction HDR brachytherapy.Materials and methodsThe medical records of all consecutive patients treated with curative-intent HDR brachytherapy for a LACC in a French Cancer Center were retrospectively reviewed.ResultsThirty-eight LACC patients underwent a 5-fraction intracavitary HDR brachytherapy between 2015 and 2019 (median dose = 25 Gy/5 fractions, following external-beam radiotherapy). Median age at diagnosis was 60 (range: 29–87). Thirty-one patients (81.5%) underwent concurrent chemotherapy. Tumor stages ranged from 3 IB2 (7.8%), 4 IB3 (10.5%), 4 IIA2 (10.5%), 12 IIB (31.7%), 1 IIIA (2.6%), 2 IIIB (5.3%), 7 IIIC1 (18.5%), 4 IIIC2 (10.5%), 1 IVA (2.6%) (2018 FIGO). Median D90% to CTV_HR reached 79.5 Gy (EQD2). Median D90% to CTV_IR reached 59.5 Gy (EQD2). Median Bladder D2cc was 69.8 Gy (EQD2). Median Rectum D2cc was 58.3 Gy (EQD2). Acute/late grade 3 toxicity was reported in one patient (2.6%). No grade 4–5 toxicity occurred. At a median 38 months follow-up, 10 patients (26.3%) had local (n = 7, 18.4%), nodal (n = 6, 15.7%) and/or distant (n = 7, 18.4%) relapse. Three-year overall survival rate was of 81.6%.ConclusionThe 5-fraction HDR scheme was well tolerated even in frail patients. Three-year local control was lower than expected. Treatment (absence of parametrial interstitial implants and use of cervical EBRT boost) and patients’ characteristics (age, comorbidities) may explain such results.     

Tolerance and efficacy of dose escalation using IMRT combined with chemotherapy for unresectable esophageal carcinoma: Long-term results of 51 patients

PurposeThe optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60 Gy delivered with intensity-modulated radiotherapy (IMRT).Materials and methodsAll consecutive patients that received a definitive CRT > 50 Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis.ResultsA total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60 Gy (54–66) and 48 Gy (44.8–56) delivered in 30 (27–35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4 Gy (IC 95%: 4.8–19.8), the median volumes receiving up to 20 Gy (V20) and 30 Gy (V30) were 13.5% (3.0–46.0) and 4.6% (0.7–19.8) respectively. The mean dose delivered to the heart was 13.9 Gy (IC 95%:0.3–31.3) with a median V40 of 3.3% (0.0–25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9–4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤ grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%).ConclusionWe demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.     

Transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma: Long-term results of RTF3 regimen

PurposeIn early-stage hepatocellular carcinoma (HCC) patients merely fit for surgery, transarterial chemoembolization (TACE) achieve low long-term disease control. We evaluated the efficacy and safety of its combination with moderately hypofractionated radiotherapy (hRT) using RTF3 regimen.Material and methodsBetween 2006 and 2016, 61 consecutive patients treated in our single expert center for a Barcelona Clinic Liver Cancer (BCLC) A HCC by TACE followed by hRT 3 Gy/fraction were retrospectively included.ResultsSixty of the 61 included presented Child-Pugh A cirrhosis (A5, n = 41, 67.2%; A6: n = 19, 31.1%). Fourteen patients (22.9%) were already treated for a HCC, mainly by radiofrequency (n = 12). All patient received a TACE followed by 3 Gy per fraction hRT. Mean radiation dose was 54 Gy (range: 48–60). After a median follow-up of 118 months, median time-to-progression, progression-free survival (PFS) and overall survival (OS) was 21.3, 18.1, and 31.5 months, respectively. In univariate analysis, PFS was related to dose > 54 Gy (HR: 2, P = 0.036), and OS was correlated to Child-Pugh A6 or B7 (HR: 1.93, P = 0.03) and overall hRT time (HR: 1.06, P = 0.015). At progression, orthotopic liver transplantation was performed in 8 patients (13.1%). Severe symptomatic adverse events occurred in 12 patients (19.7%), mainly ascites (n = 7).ConclusionIn BCLC-A Child-Pugh A HCC patients ineligible to surgery or thermoablation, TACE-hRT is a safe and effective treatment. Prospective studies are needed to compare this association with radioembolization, TACE-stereotactic radiotherapy, and systemic treatments combinations.     

Outcome of radiotherapy for invasive bladder cancer in older patients – not candidates for or decline cystectomy

PurposeRetrospective study to assess the role of radiotherapy (RT) in bladder cancer (BC) in patients who decline cystectomy or for whom it was contraindicated, regarding BC related events.Materials and MethodsA cross-sectional study, of patients with BC treated with RT, with or without chemotherapy was carried out, during the period March 2005 to March 2017, excluding patients who performed cystectomy. BC-related events were defined as haematuria, episodes requiring intravesical irrigations or transurethral resection or admission in Urology Department caused by symptoms related to BC.ResultsFifty-eight patients were included, 44 men and 14 women, whose median age at diagnosis was 78.3 years. Nine patients were treated with a RT dose below 50 Gy (20-45 Gy), in relation with non-resectable disease, nodal involvement, presence of metastasis or poor performance status. Forty-nine patients were treated with a RT dose above 50 Gy (maximum 60.4 Gy). The median follow-up time was 24 months, with BC-specific survival at 1/5 years of 87.5%/0.0% and 83.1%/33.9% in the group treated with RT dose below 50 Gy and above 50 Gy, respectively. Results revealed that the number of events decreased significantly after RT for both groups. For the two groups, the median of events before RT was 2.0, decreasing for 1.0 after RT (RT dose < 50 Gy: P = 0.011; RT dose ≥ 50 Gy: P = 0.026).ConclusionThis therapeutic approach can have an important role in older patients with bladder cancer, in terms of reducing disease related events. Symptom control was significantly achieved in both therapeutic groups.     

Stereotactic radiotherapy for large solitary brain metastases

PurposeTo assess effectiveness and toxicity levels of stereotactic radiation therapy without whole brain radiation therapy in patients with solitary brain metastases larger than 3 cm.Patients and methodsBetween June 2007 and March 2009, 12 patients received fractionated stereotactic radiation therapy and 24 patients underwent stereotactic radiosurgery. For the fractionated stereotactic radiation therapy group, 3 × 7.7 Gy were delivered to the planning target volume (PTV); median volume and diameter were 29.4 cm³ and 4.4 cm, respectively. For the stereotactic radiosurgery group, 14 Gy were delivered to the PTV; median volume and diameter were 15.6 cm³ and 3.7 cm, respectively.ResultsMedian follow-up was 218 days. For the fractionated stereotactic radiation therapy group, local control rates were 100% at 360 days and 64% at 720 days; for the stereotactic radiosurgery group, rates were 58% at 360 days and 48% at 720 days (P = 0.06). Median survival time was 504 days for the fractionated stereotactic radiation therapy group and 164 days for the stereotactic radiosurgery group (P = 0.049). Two cases of grade 2 toxicity were observed in the fractionated stereotactic radiation therapy group, and 6 cases of grade 1–2 toxicity, in the stereotactic radiosurgery group.ConclusionsThis study provides data to support that fractionated stereotactic radiation therapy without whole brain radiation therapy with a margin dose of 3 fractions of 7.7 Gy for treatment of solitary large brain metastases is efficient and well-tolerated. Because of the significant improvement in overall survival, this schedule should be assessed in a randomized trial.     

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Toxicity and early clinical outcomes in cervical cancer following extended field helical tomotherapy to para-aortic lymph nodes

PurposeTo evaluate toxicity and early disease outcome among patients treated for cervical cancer with extended-field helical tomotherapy to the para-aortic nodes.Patients and methodsThirty-eight patients (International Federation of Gynecology and Obstetrics [FIGO] stage IB2–IVA) from four institutions received extended-field helical tomotherapy and were retrospectively evaluated. All had nodal disease. Para-aortic lymph nodes were involved in 31 patients. Patients were assessed for toxicity using version 4 of the National Cancer Institute's common terminology criteria for adverse events. Survival curves were plotted using Kaplan-Meier estimates.ResultsAll patients underwent radiation to the tumor region (median dose: 45 Gy; range: 44–66 Gy), pelvic lymph nodes and para-aortic lymph nodes (median dose: 45 Gy; range: 44–60 Gy). The median dose to positive lymph nodes was 55 Gy (range: 45–65 Gy). All received platinum-based chemotherapy (31 concurrently). The median follow-up was 15 months. Acute toxicity events observed included one patient with grade 5 febrile neutropenia, 11 patients (29%) with grade 3 hematologic complications. Grades 3–4 gastrointestinal and genitourinary toxicities occurred in six (16%) and four (11%) patients, respectively. Three patients had grade 3 pelvic pain (8%). The 6- and 18-month overall survival rates were 94.7 and 63.9%, respectively. The 18-month locoregional control, disease-free survival, and late grade 3 toxicity rates were 60.2, 43.3 and 7.3%, respectively.ConclusionExtended-field helical tomotherapy was associated with low rates of acute gastrointestinal and genitourinary toxicities with early survival and locoregional control similar to other published series.     

Dose distribution of the brain tissue associated with cognitive functions in high-grade glioma patients

PurposeThe purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT).Patients and methodsThirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60 Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test.ResultsConformity indexes remained similar with both techniques. The mean values were 0.96 (0.19–1.00) for VMAT and 0.98 (range, 0.84–1.00) for HT, respectively (P = 0.73). Significant D_50% reductions were observed with VMAT compared to HT: 14.6 Gy (3.8–28.0) versus 17.4 Gy (12.1–25.0) for the normal brain (P = 0.014); 32.5 Gy (10.3–60.0) versus 35.6 Gy (17.1–58.0) for the corpus callosum (P = 0.038); 8.1 Gy (0.4–34.0) versus 12.8 Gy (0.8–27.0) for the cerebellum (P < 0.001), respectively.ConclusionThe VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.     

Radiation dose to the low axilla in patients treated for early-stage breast cancer by locoregional intensity-modulated radiotherapy (IMRT)

PurposeTo determine the dose received by the low axilla during locoregional radiotherapy (RT) for early-stage breast cancer and to assess the impact of the treatment technique (three-dimensional conformal radiotherapy (3D-CRT) or rotational IMRT (VMAT) or helical tomotherapy (HT).Materials and methodsThe dosimetric study was performed on patients receiving normofractionated (NFRT - 50 Gy in 25 fractions) or hypofractionated (HFRT - 40 Gy in 15 fractions) locoregional radiotherapy (breast or chest wall and internal mammary, supraclavicular and infraclavicular nodes ± axillary nodes) by 3D-CRT or VMAT or HT at the Institut Curie Paris. Patients treated by breast-conserving surgery received a boost dose of 16 Gy and 10 Gy to the tumour bed, respectively.ResultsSixty-eight patients treated by RT from February 2017 to January 2019 were studied. The mean dose received by the low axilla when it was not part of the target volume was 30.8 Gy, 41.0 Gy and 44.4 Gy by 3D-CRT, VMAT and HT, respectively for NFRT and 24.2 Gy, 33.0 Gy and 34.9 Gy, respectively, for HFRT. With NFRT, 4.1% of the axilla received 95% (V95) of the prescribed dose by 3D-CRT compared to 24.5% and 33.6% by VMAT and HT, respectively; with HFRT, V95 was 3.9%, 19.5% and 24.1%, respectively.ConclusionThe axilla receives a non-negligible dose during locoregional radiotherapy; this dose is greater when VMAT or HT are used. Prospective studies must be conducted to assess the impact of this axillary dose in terms of morbidity, which currently remains unknown.     

High dose rate brachytherapy with customized applicators for malignant facial skin lesions

PurposeBrachytherapy is a well-known treatment in the management of skin tumors. For facial or scalp lesions, applicators have been developed to deliver non-invasive treatment. We present cases treated with customized applicators with high dose rate system.Material and methodsPatients with poor performance status treated for malignant skin lesions of the scalp or the facial skin between 2011 and 2014 were studied. Afterloading devices were chosen between Freiburg^® Flap, silicone-mold or wax applicators. The clinical target volume (CTV) was created by adding margins to lesions (10 mm to 20 mm). The dose schedules were 25 Gy in five fractions for postoperative lesions, 30 Gy in six fractions for exclusive treatments and a single session of 8 Gy could be considered for palliative treatments.ResultsIn 30 months, 11 patients received a treatment for a total of 12 lesions. The median age was 80 years. The median follow-up was 17 months and the 2-year local control rate was 91%. The mean CTV surface was 41.1 cm² with a mean thickness of 6.1 mm. We conceived three wax applicators, used our silicone-mold eight times and the Freiburg^® Flap one time. We observed only low-grade radiodermitis (grade I: 50%, grade II: 33%), and no high-grade skin toxicity.ConclusionHigh dose rate brachytherapy with customized applicators for facial skin and scalp lesions is efficient and safe. It is a good modality to treat complex lesions in patients unfit for invasive treatment.     

Survival comparision of three-dimensional radiotherapy alone with concurrent chemoradiotherapy for non-surgical esophageal carcinoma

PurposeRadiotherapy is the main treatment method for patients with locally advanced, unresectable esophageal cancer. The aim of this study is to compare overall survival (OS) using 3D radiotherapy (3DRT) alone with concurrent chemoradiotherapy (CCRT) in 296 non-surgical esophageal carcinoma patients.Patents and methodsOver 10 years, of the 480 patients with esophageal carcinoma treated with 3DRT with or without chemotherapy, 148 patients each comprised 3DRT and CCRT groups after propensity score matching.ResultsThe 5- and 10-year OS (P = 0.337) and PFS (P = 0.715) rates for 3DRT alone were 22.0%, 14.4% and 26.1%, 23.2%, respectively, compared with 28.8%, 18.6% and 34.7%, 29.1% for CCRT, respectively. CCRT did not improve 5-year and 10-year OS or PFS in 60–70 Gy group (OS: 27.5% and 25.2%; 17.9% and 17.0%, P = 0.938; PFS: 38.3% and 31.8%; 31.9% and 27.8%, P = 0.890) nor reduce 10-year hematogenous metastasis (31.7% and 28.3%, P = 0.698). CCRT improved 5-year OS and PFS of 50.0–59.9 Gy group (OS: 33.3% and 12.0%, P = 0.029; PFS: 33.1% and 10.6%, P = 0.081). For 3DRT, the 5-year OS and PFS rates were significantly better in the 60–70 Gy group (P = 0.017) compared with 50.0–59.9 Gy group (P = 0.002). For CCRT group, 5-year OS and PFS favored the 50.0–59.9 Gy group, but the difference was insignificant. Major toxicities were greater with CCRT compared with 3DRT.ConclusionFor non-surgical esophageal carcinoma patients, 3DRT combined with CCRT was effective in prolonging both OS and PFS.     

Comparison of passive-beam proton therapy,helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy

PurposeSecond cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy.Patients and methodsFourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30 Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20 Gy/10 Gy.ResultsMean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15 Gy with the V_20 Gy equal to 16.4%, compared to 19.7% for proton therapy (P = 0.01) or 22.4% with 3D conformal radiation therapy (P < 0.01). Volumes of lung receiving doses below 15 Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V_10 Gy = 37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10 Gy or more than 4 Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V_4 Gy representing more than a third of one breast volume with helical tomotherapy.ConclusionsHelical tomotherapy achieved a better protection to the lungs for doses above 15 Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.     

Implementation of an optimization method for parotid gland sparing during inverse planning for head and neck cancer radiotherapy

PurposeTo guide parotid gland (PG) sparing at the dose planning step, a specific model based on overlap between PTV and organ at risk (Moore et al.) was developed and evaluated for VMAT in head-and-neck (H&N) cancer radiotherapy.Materials and methodsOne hundred and sixty patients treated for locally advanced H&N cancer were included. A model optimization was first performed (20 patients) before a model evaluation (110 patients). Thirty cases were planned with and without the model to quantify the PG dose sparing. The inter-operator variability was evaluated on one case, planned by 12 operators with and without the model. The endpoints were PG mean dose (D_mean), PTV homogeneity and number of monitor units (MU).ResultsThe PG D_mean predicted by the model was reached in 89% of cases. Using the model significantly reduced the PG D_mean: −6.1 ± 4.3 Gy. Plans with the model showed lower PTV dose homogeneity and more MUs (+10.5% on average). For the inter-operator variability, PG dose volume histograms without the optimized model were significantly different compared to those with the model; the D_mean standard deviation for the ipsilateral PG decreased from 2.2 Gy to 1.2 Gy. For the contralateral PG, this value decreased from 2.9 Gy to 0.8 Gy.ConclusionDuring the H&N inverse planning, the optimized model guides to the lowest PG achievable mean dose, allowing a significant PG mean dose reduction of −6.1 Gy. Integrating this method at the treatment-planning step significantly reduced the inter-patient and inter-operator variabilities.     

Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study

PurposeThe use of intensity-modulated radiotherapy (IMRT) to treat cervix carcinoma has increased, however prospective randomized trials are still lacking.AimTo compare the dosimetric parameters and associated acute toxicity in patients with cervix carcinoma treated with three-dimensional (3D) conformal radiotherapy and IMRT.Patients and methodsForty patients were randomized in two arms each consisting of 20 patients. Patients in both arms received concurrent chemoradiation (cisplatin 40 mg/m² weekly; 50 Gy/25 fractions). Patients were treated with 3D conformal radiotherapy in one arm and with IMRT in another arm. After external beam radiotherapy, all patients received brachytherapy (21 Gy/3 fractions at weekly interval). For dosimetric comparison, both kinds of the plans were done for all the patients. All patients were assessed throughout and until 90 days after completion of treatment for acute gastrointestinal, genitourinary and hematologic toxicities.ResultsBoth plans achieved adequate planning target volume coverage, while mean conformity index was found significantly better in IMRT plans (P-value = 0.001). D₃₅ (dose to 35% volume) and D₅₀ for bladder was reduced by 14.62 and 32.57% and for rectum by 23.82 and 43.68% in IMRT. For IMRT, V₄₅ (volume receiving 45 Gy) of bowel were found significantly lesser (P-value = 0.0001), non-tumour integral dose was found significantly higher (P-value = 0.0240) and V₂₀ of bone marrow was found significantly reduced (P-value = 0.019) in comparison to that in 3D conformal radiotherapy. Significant reduction of grade 2 or more (20 vs 45%; P-value = 0.058) and grade ≥ 3 (5 vs 15%, P-value = 0.004) acute genitourinary toxicity and grade 2 or more (20 vs 45%, P-value = 0.003) and grade 3 or more (5 vs. 20%, P-value = 0.004) acute gastrointestinal toxicity while no significant difference for grade 2 and 3 or more haematological toxicity was noted in patients treated with IMRT compared to 3D conformal radiotherapy.ConclusionIMRT provide a good alternative for treatment of cervix carcinoma with lower acute gastrointestinal and acute genitourinary toxicity with similar target coverage compared to 3D conformal radiotherapy.     

Hypofractionated stereotactic radiotherapy for challenging brain metastases using 36 Gy in six fractions

PurposeStereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3 cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6 Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15 cm³) or brain metastases located next to critical structures.Material and methodsPatients with brain metastases treated with the 6 × 6 Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated.ResultsSixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N = 5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity.ConclusionThe 6 × 6 Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.