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.     

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.     

Myths,facts and scope of spinal cord tolerance dose revision in Intensity modulated SIB treatment of locally advanced head and neck cancer: A dosimetrical and radiobiological demonstration

PurposeTo explore the possibility of revising the spinal cord tolerance dose in Simultaneously Integrated Boost (SIB) intensity modulated treatment plan of locally advanced head and neck (H&N) cancer and assessment of achieved planning gain due to the revision. In SIB regimen, the Organ at Risk (OARs) tolerance dose is equally distributed throughout the treatment. Clinicians have usually considered the spinal cord tolerance to be the same as in conventional technique. However, in SIB fractionation regimen with intensity modulation treatment, the spinal cord may receive a physical dose of 45 Gy, with much lesser dose per fraction than 2 Gy per fraction. So when the dose of spinal cord is distributed throughout the treatment, the tolerance dose limit of physical dose can be considered higher than the usual conventional dose limits. In this study, an attempt has been made to explore the possibilities of dose escalation and treatment planning benefits while exploiting this “Window of Opportunity (WoO)” of increase in spinal cord and Planning Risk Volume (PRV) spinal cord tolerance dose.Material and methodsA total of 12 patients CT data set along with approved structure set of H&N cancer used for treatment planning in. Three independent SIB VMAT plans named as SPC, SPR and SPDE were generated for the 12 patients. First plan (SPC) was generated by considering standard spinal cord tissue constraint of maximum dose of 45 Gy and PRV spinal cord maximum dose 50 Gy as per QUANTEC summary and second plan (SPR) was generated considering spinal cord tissue constraint of maximum dose 52.50 Gy and PRV spinal cord maximum dose 56.35 Gy while optimization and dose calculation. The objectives for rest of the Organ at Risk (OAR) were kept same in both the plans during optimization and dose calculation. The SPC plan was copied for creation of third plan (SPDE) in which dose was escalated by increasing dose per fraction for target volumes such that dose to spinal cord reached a maximum dose of 52.50 Gy and PRV spinal cord maximum dose of 56.35 Gy. In this plan there have been changes to only dose per fraction, however dose optimization and dose calculation have not been performed. Radiobiological parameters TCP and NTCP were also calculated by using indigenously developed software.ResultsConsidering the increase of spinal cord tolerance dose as “window of opportunity”, a sufficient escalation in physical dose, Biological Effective Dose (BED) and Tumor Control Probability (TCP) was observed for all target volumes with acceptable level of NTCP values.ConclusionSufficient dose escalation and increased in TCP for target volumes or effective planning benefits can be achieved by revising the spinal cord tolerance dose in intensity modulated SIB treatment of locally advanced H&N cancers.     

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.     

Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

Background and purposeTo identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer.Materials and methodsWe analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models.ResultsNadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p = 0.04), and patients ⩾59 years of age had a lower hemoglobin ratio trend during PRT (p = 0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p = 0.03), and women had lower hemoglobin cell count trend compared to men (p = 0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p = 0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p = 0.03) and sacral BM V45 (p = 0.03) were associated with a lower WBC and ANC ratio at nadir, respectively.ConclusionsHT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered.     

Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.     

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.     

Tomothérapie hélicoïdale dans le traitement du mésothéliome pleural malin : impact des faibles doses sur la toxicité pulmonaire et œsophagienne

PurposeTo evaluate the adjuvant treatment of malignant pleural mesothelioma by helical tomotherapy and the impact of low doses on esophageal and pulmonary toxicity.Patients and methodsBetween June 2007 and May 2011, 29 patients diagnosed with malignant pleural mesothelioma received adjuvant radiotherapy by helical tomotherapy. The median age was 63 years (34–72). Histologically, 83 % of patients had epithelioid malignant pleural mesothelioma. Clinically, 45 % of patients were T3 and 55 % N0. Eighty six percent of the patients were treated by extrapleural pneumonectomy and 35 % received neoadjuvant chemotherapy with platinum and pemetrexed. The median dose in the pneumonectomy cavity was 50 Gy at 2 Gy/fraction.ResultsThe mean follow-up was 2.3 years after diagnosis. Overall survival at 1 and 2 years was 65 and 36 % respectively. The median survival from diagnosis was 18 months. Median lung volumes receiving 2, 5, 10, 13, 15 and 20 Gy (V2, V5, V10, V13, V15 and V20) were 100, 98, 52, 36, 19 and 5 %. The median of the mean remaining lung dose was 11 Gy. Two patients died of pulmonary complications, three patients had grade 3 lung toxicity, while esophageal grade 3–4 toxicity was observed in three other patients. No significant impact of clinical characteristics and dosimetric parameters were found on pulmonary toxicity, however a V10 ≥ 50 %, a V15 ≥ 15 % and mean lung dose of 10 Gy or more had a tendency to be predictive of pulmonary toxicity (P < 0.1). Moreover, in our analysis, the mean lung dose seems to have a significant impact on esophageal toxicity (P = 0.03) as well as low doses to the controlateral lung: V5, V10 and V13 (P < 0.05).ConclusionHelical tomotherapy is a promising technique in the multimodality treatment of malignant pleural mesothelioma. Low doses received by the contralateral lung appear to be the limiting factor. A dosimetric comparison with volumetric modulated arctherapy techniques would be interesting in this setting.     

Radiothérapie stéréotaxique des métastases osseuses du squelette périphérique

PurposeStereotaxic radiotherapy is performed regularly for the irradiation of non-spine bone metastases, but its place is not well understood.Materials and methodsThis article in stereotaxic radiotherapy of non-spine bones oligometastases presents the current scientific data relating to the indications, to virtual simulation, to the delineation of target volumes, to the total dose and fractionation, to the efficacy and tolerance.ResultsOligometastatic patients are classified into 4 categories: oligorecurrences, oligometastasis, oligopersistence, oligoprogression. The prognosis will be evaluated according to the following characteristics: primary tumor, quantitative characteristics, kinetics, qualitative characteristics. The delineation of GTV includes extensions to the soft tissue and bone marrow with the aid of MRI and PET. The CTV corresponds to a margin of 2 to 5 mm and the PTV to a margin of 2 mm. The most widely used irradiation schemes are: 1 single fraction of 18 to 24 Gy/1 fr; 24 Gy/2 fr; 27 to 30 Gy/3 fr; 30 to 35 Gy/5 fr. Stereotaxis provides 90% local control at 1 year and good pain control. The side effects are not very marked.ConclusionStereotaxic radiotherapy is feasible, non-invasive, minimally toxic and effective with good local control and good pain relief. The main issue remains selecting the patients most likely to benefit from it.     

Irradiation axillaire prophylactique « de diffusion » dans le cancer du sein — revue de la littérature

PurposeIn breast cancer, radiotherapy is an essential component of the treatment. However, indications of irradiation of the internal mammary chain and axillary area are debatables. Axillary recurrence in patients with invasive breast carcinoma remains an issue. Currently, the substitution of axillary lymph node dissection by sentinel node biopsy leads to revisit the role of axillary irradiation. Breast irradiation including level I, II and III might decrease the risk of axillary recurrence.Material and methodsA literature search was performed in PubMed and the Cochrane library to identify articles publishing data regarding dose-volume analysis of axillary levels in breast irradiation aiming to determine the potential therapeutic implications.ResultsEleven articles were retained. A total of 375 treatment plans were analyzed. The results concerning the irradiation technique, initial dose prescribed to breast, delineated volumes and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I–III with 3D-conformal radiotherapy using standard fields were between 24 Gy and 43.5 Gy, 3 Gy and 32.5 Gy and between 1.0 Gy and 20.5 Gy respectively. The average doses delivered to axilla levels I–III with 3D-conformal radiotherapy using high tangential fields were between 38 Gy and 49.7 Gy, 11 Gy and 47.1 Gy and 5 Gy 38.7 Gy, 32.1 Gy and 5 Gy (result available for only one study) respectively. Finally, the average doses delivered to axilla levels I–III with intensity modulated radiation therapy were between 14.5 Gy and 42.6 Gy, 3.4 Gy and 35 Gy and between 1.2 Gy and 25.5 Gy respectively.ConclusionsIncidental axillary dose seems insufficient to be therapeutic regardless of the irradiation technique. There are meaningful differences between intensity modulated radiation therapy and 3D-conformal radiotherapy.     

Clinical experience in pediatric neuroblastoma intensity modulated radiotherapy

BackgroundIn spite of the numerous publications of dosimetric comparison of intensity modulated radiotherapy (IMRT) versus conventional radiotherapy in pediatrics, few data exist regarding the clinical use of IMRT and its potential late effects.ProcedurePediatric neuroblastoma patients treated between November 2008 and October 2010 with IMRT were reviewed. Treatment plans, clinical, laboratory and radiological data at the last follow up date were evaluated.ResultsThirteen patients received IMRT. The mean age was 4.9 ± 2 years. The radiation dose ranged from 21 to 25.5 Gy with a mean dose of 24.06 Gy. The mean liver dose was 9.81 Gy. The V8 of the liver was 51 ± 20%, and the V15 of the liver was 21 ± 12%. V18 of the right and left kidneys were 32 ± 27% and 23 ± 18% respectively. The minimum and maximum vertebral point doses were 12.82 and 24.87 Gy respectively. The IMRT treatment was well tolerated in terms of acute toxicity. At 26 month follow up, second malignancy and skeletal asymmetry were not noted, and the liver and the kidney functions showed no significant abnormalities.ConclusionsThe use of IMRT in pediatric neuroblastoma confers higher target conformality with better sparing of the kidneys and it did not show any considerable short term side effects.     

Intensity-modulated Radiotherapy Allows Escalation of the Radiation Dose to the Pelvic Lymph Nodes in Patients with Locally Advanced Prostate Cancer: Preliminary Results of a Phase I Dose Escalation Study

AimPelvic irradiation in addition to prostate irradiation may improve outcome in locally advanced prostate cancer, but is associated with dose-limiting bowel toxicity. We report the preliminary results of a dose escalation study using intensity-modulated radiotherapy.Materials and methodsEligible patients had high-risk (T3, Gleason ≥8 or prostate-specific antigen ≥20 ng/ml) or lymph node-positive disease. Intensity-modulated radiotherapy was inverse planned giving 70 Gy/35 fractions to the prostate and 50 Gy/55 Gy/60 Gy in sequential cohorts to the pelvis with a 5 Gy boost to positive lymph nodes. Acute and late toxicity were recorded with Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue - Subjective Objective Management LENT-SOM scales. Neoadjuvant androgen suppression was given for 3 years. This report concerns the 50 and 55 Gy cohorts.ResultsSeventy-nine men were recruited (25 to 50 Gy/54 to 55 Gy) with a median follow-up of 2 years. Patients were divided into two groups according to the total bowel volume outlined (median 450 cm³). Acute RTOG (≥2) bowel toxicity was 40 and 50% for the 50 and 55 Gy groups and 38 and 51% for bowel volume <450 cm³ and ≥450 cm³, respectively, suggesting both volume and dose relationships for acute effects. Late RTOG diarrhoea ≥grade 2 was only seen with bowel volume ≥450 cm³, but no dose effect was apparent (12%/50 Gy and 10%/55 Gy). LENT-SOM bowel ≥grade 2 toxicity occurred in 22%/50 Gy and 15%/55 Gy. Only one patient had grade 3 toxicity. A dose volume histogram analysis showed increased late RTOG diarrhoea ≥grade 2 with larger bowel volume irradiated, significant for BV40 >124 cm³ (P = 0.04), BV45 >71 cm³ (P = 0.03) and BV60 >2 cm³ (P = 0.01).ConclusionsAcute and late bowel toxicity was acceptably low using a pelvic dose of up to 55 Gy over 7 weeks. Both relate to total pelvic bowel volume and dose volume constraints have been defined.     

Comparison between the HyperArc™ technique and the CyberKnife® technique for stereotactic treatment of brain metastases

PurposeThe purpose of this study was to compare the planimetric capacities between HyperArc™-based stereotactic radiosurgery and robotic radiosurgery system-based planning using CyberKnife® M6 for single and multiple cranial metastases.Materials and methodsWe evaluated 51 treatment plans for cranial metastases, including 30 patients with a single lesion and 21 patients with multiple lesions, treated with the CyberKnife® M6. These treatment plans were optimized using the HyperArc™ (HA) system with the TrueBeam. The comparison of the quality of the treatment plans between the two treatment techniques (CyberKnife and HyperArc) was performed using the Eclipse treatment planning system. Dosimetric parameters were compared for target volumes and organs at risk.ResultsCoverage of the target volumes was equivalent between the two techniques, whereas median Paddick conformity index and median gradient index for all target volumes were 0.9 and 3.4, respectively for HyperArc plans, and 0.8 and 4.5 for CyberKnife plans (P < 0.001). The median dose of gross tumor volume (GTV) for HyperArc and CyberKnife plans were 28.4 and 28.8, respectively. Total brain V18 Gy and V12Gy-GTVs were 11 cm³ and 20.2cm³ for HyperArc plans versus 18 cm³ and 34.1 cm³ for CyberKnife plans (P < 0.001).ConclusionThe HyperArc provided better brain sparing, with a significant reduction in V12 Gy and V18 Gy, associated with a lower gradient index, whereas the CyberKnife gave a higher median GTV dose. The HyperArc technique seems to be more appropriate for multiple cranial metastases and for large single metastatic lesions.     

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.     

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.     

Chimioradiothérapie exclusive pour cancer de l’œsophage : comparaison entre 66 Gy et 50 Gy,une étude rétrospective

PurposeTo compare the influence of radiation dose, high dose versus standard dose, on survival for patients with esophageal carcinomas treated with definitive radiochemotherapy.Patients and methodsBetween 2003 and 2006, 143 consecutive patients with squamous-cell carcinoma and adenocarcinoma, clinical stage I to IVA, treated in two different institutions were retrospectively reviewed, 83 patients had received more than 50.4 Gy, median dose 66 Gy (50.7–72 Gy) and 60 less than or equal to 50.4 Gy, median dose 50 Gy (38–50.4 Gy).ResultsMedian age was higher in high dose group (67.6 versus 61.7 years). Nutritional status and stage were better in high dose group with a lower weight loss (5.1 versus 7.9%), a higher body mass index (25.7 versus 22.9), more N0 patients (60.2 versus 31.7%) and less stage III (27.7 versus 63.3%). Median follow up was 20.8 months (2.8–92.4 months), and 64.9 months (4.2–92.4 months) for the 33 surviving patients. No statistically significant difference was shown for local/locoregional control, disease-free survival. Overall survival at 2-, 3- and 5-year and median survival was respectively 44.7%, 36.8%, 19.1% and 21.2 months in high dose group and 50.8%, 31.6%, 20.7% and 24.6 months in standard dose group (P = 0.9).ConclusionNo difference was found between the two groups in terms of local/distant control and overall survival. A prospective randomised study is needed.     

Outcomes in paediatric metastatic rhabdomyosarcoma: Results of The International Society of Paediatric Oncology (SIOP) study MMT-98

PurposeResults are presented of the SIOP study MMT-98 for paediatric metastatic rhabdomyosarcoma (RMS), which evaluated intensive chemotherapy followed by low intensity ‘maintenance’ chemotherapy in standard risk patients (SRG). For poor risk patients (PRG), the value of a therapeutic window study, sequential high dose monotherapy to achieve a complete response (CR) followed by low dose maintenance chemotherapy was examined.Patients and methodsFrom November 1998 to 2005, 146 patients aged 6 months to 18 years with metastatic RMS were entered. Forty-five were SRG, i.e. age < 10 years and no bone marrow or bone involvement. Treatment was a 6-drug regimen with local therapy of surgery and/or radiotherapy followed by maintenance of 9 courses of vincristine, actinomycin D and cyclophosphamide (VAC). One hundred and one patients were PRG, i.e. >10 years, or with bone marrow or bone metastases. An upfront window study, high dose monotherapy, local treatment and then VAC maintenance therapy were given.ResultsWith a median follow-up of 1.52 years, the 3-year event-free survival (EFS) and overall survival (OS) for SRG were 54.92% and 62.14%, respectively, whilst for the PRG 16.17% and 23.17%. The corresponding adverse hazard ratio (HR) for the PRG was HR = 2.65 (95% CI 1.63–4.31, p-value < 0.001) for EFS and HR = 2.51 (CI 1.53–4.11, p-value < 0.001) for OS.ConclusionSRG patients’ EFS and OS were comparable to those of previous studies. For PRG patients there was no improvement in survival.     

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 analysis of urethral strictures following HDR 192Ir brachytherapy as monotherapy for intermediate- and high-risk prostate cancer

Background and purposeTo evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer.Material and methodsTen strictures were identified in 213 patients treated with HDRBT alone receiving 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in 3 fractions or 26 Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra.ResultsStricture rates were 3% in the 34 Gy group, 4% in the 36 Gy group, 6% in the 31.5 Gy group and 4% in the 26 Gy group. The median time to stricture formation was 26 months (range 8–40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule.ConclusionsUrethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions.