Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions

PURPOSE: To assess the prevalence and dosimetric and clinical predictors of mandibular osteoradionecrosis (ORN) in patients with head and neck cancer who underwent a pretherapy dental evaluation and prophylactic treatment according to a uniform policy and were treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 1996 and 2005, all patients with head-and-neck cancer treated with parotid gland-sparing IMRT in prospective studies underwent a dental examination and prophylactic treatment according to a uniform policy that included extractions of high-risk, periodontally involved, and nonrestorable teeth in parts of the mandible expected to receive high radiation doses, fluoride supplements, and the placement of guards aiming to reduce electron backscatter off metal teeth restorations. The IMRT plans included dose constraints for the maximal mandibular doses and reduced mean parotid gland and noninvolved oral cavity doses. A retrospective analysis of Grade 2 or worse (clinical) ORN was performed. RESULTS: A total of 176 patients had a minimal follow-up of 6 months. Of these, 31 (17%) had undergone teeth extractions before RT and 13 (7%) after RT. Of the 176 patients, 75% and 50% had received >or=65 Gy and >or=70 Gy to >or=1% of the mandibular volume, respectively. Falloff across the mandible characterized the dose distributions: the average gradient (in the axial plane containing the maximal mandibular dose) was 11 Gy (range, 1-27 Gy; median, 8 Gy). At a median follow-up of 34 months, no cases of ORN had developed (95% confidence interval, 0-2%). CONCLUSION: The use of a strict prophylactic dental care policy and IMRT resulted in no case of clinical ORN. In addition to the dosimetric advantages offered by IMRT, meticulous dental prophylactic care is likely an essential factor in reducing ORN risk.     

Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective,multi-centre,International Extranodal Lymphoma Study Group study

BackgroundWe evaluated the long-term results of radiotherapy for patients with gastric marginal zone lymphoma (GMZL).Patients and methodsWe carried out a retrospective, multi-centre study of patients with low-grade GMZL treated by radiotherapy between 17 July 1981 and 25 March 2004.ResultsThere were 102 eligible patients. Fifty-eight patients were previously untreated and 44 had recurrent/residual disease after prior treatment (HP eradication, chemotherapy and surgery in 35, 9 and 8 patients, respectively, and 7 had >1 prior therapy). Radiation fields included the stomach /involved nodes in 61 patients and whole abdomen in 41. The median radiotherapy dose to stomach was 40 Gy (range 26–46 Gy) in a median 22 fractions. With a median follow-up after radiotherapy of 7.9 years (range 0.3–24 years), 10- and 15-year freedom from treatment failure (FFTF) was 88% (95% CI 82%–95%). Risk factors for TF were a large-cell component (P = 0.036) and an exophytic growth pattern (P = 0.042). Radiotherapy field size, radiotherapy dose, and failure of prior therapy were not associated with inferior FFTF. Ten-year overall survival was 70% (95% CI 60%–82%).ConclusionsRadiotherapy achieves cure for the majority of patients with low-grade GMZL, including patients who have had prior therapy. Several features may predict a poorer outcome.     

Consolidative proton therapy after chemotherapy for patients with Hodgkin lymphoma

BackgroundWe investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL).Patients and methodsFrom June 2008 through August 2015, 138 patients with HL enrolled on either IRB-approved outcomes tracking protocols or registry studies received consolidative PT. Patients were excluded due to relapsed or refractory disease. Involved-site radiotherapy field designs were used for all patients. Pediatric patients received a median dose of 21 Gy(RBE) [range 15–36 Gy(RBE)]; adult patients received a median dose of 30.6 Gy(RBE) [range, 20–45 Gy(RBE)]. Patients receiving PT were young (median age, 20 years; range 6–57). Overall, 42% were pediatric (≤18 years) and 93% were under the age of 40 years. Thirty-eight percent of patients were male and 62% female. Stage distribution included 73% with I/II and 27% with III/IV disease. Patients predominantly had mediastinal involvement (96%) and bulky disease (57%), whereas 37% had B symptoms. The median follow-up was 32 months (range, 5–92 months).ResultsThe 3-year relapse-free survival rate was 92% for all patients; it was 96% for adults and 87% for pediatric patients (P = 0.18). When evaluated by positron emission tomography/computed tomography scan response at the end of chemotherapy, patients with a partial response had worse 3-year progression-free survival compared with other patients (78% versus 94%; P = 0.0034). No grade 3 radiation-related toxicities have occurred to date.ConclusionConsolidative PT following standard chemotherapy in HL is primarily used in young patients with mediastinal and bulky disease. Early relapse-free survival rates are similar to those reported with photon radiation treatment, and no early grade 3 toxicities have been observed. Continued follow-up to assess late effects is critical.     

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant

PurposeTo apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation.Material and methodsThe study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse ≤ 3 months; (3) ECOG-PS ≥ 1; (4) bulk ≥ 5 cm; and (5) inadequate response to salvage chemotherapy.ResultsThe median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1–7 months), and the median involved-field radiotherapy dose was 35 Gy (range, 12–40 Gy). At a median follow-up of 35 months (range, 1–132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score = 0, score = 1, score = 2, and score = 3 to 5, respectively (P = 0,01). Among the 12 patients having at least three risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis.ConclusionThe adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.     

Hypofractionated radiotherapy for non-metastatic bone and soft tissue sarcomas

PurposeTo evaluate the efficacy and toxicity of hypofractionated radiotherapy in non-metastatic soft tissue and bone sarcomas.Patients and methodsThirty patients underwent hypofractionated radiotherapy between 2007 and 2015. Overall, 17 patients underwent primary hypofractionated radiotherapy, nine underwent hypofractionated radiotherapy for reirradiation, and four received a boost dose via hypofractionated radiotherapy after external beam radiotherapy. Most common disease sites were head and neck and retroperitoneum. Hypofractionated radiotherapy was administered with a definitive, adjuvant, or neoadjuvant intent.ResultsMedian age was 37 years (range: 11–82 years). Median hypofractionated radiotherapy dose was 35 Gy (range: 20–50 Gy) in three to five fractions. Median follow-up was 21 months (range: 1–108 months). One- and 2-year overall survival rate was 75% and 52%, respectively. One- and 2-year local recurrence-free survival rate was 59% and 48%, with local recurrence rates of 16% and 33% in 1 and 2 years, respectively. Univariate analysis revealed tumour size (P = 0.04), hypofractionated radiotherapy intent (P = 0.016) and reirradiation (P = 0.001) as prognostic factors for local recurrence-free survival. Severe late toxicity was observed in one patient as grade 3 trismus.ConclusionHypofractionated radiotherapy as the primary treatment or for reirradiation has been shown to be safe in the treatment of bone and soft tissue sarcomas. It can provide relatively good local control and survival rates.     

Salivary glands radiotherapy to reduce sialorrhea in amyotrophic lateral sclerosis: Dose and energy

PurposeThis retrospective study evaluated the effectiveness of salivary gland radiotherapy for reducing sialorrhea in patients with amyotrophic lateral sclerosis (ALS).Patients and methodsFrom August 2001 to February 2008, 21 patients with amyotrophic lateral sclerosis (six men, 15 women; mean age 61.2 years, range 39–81) received external beam radiotherapy for sialorrhea (evaluation by the ALS Functional Rating Scale). All patients had previously received pharmacological treatments with unsatisfactory results or side effects. The mean dose was 19.1 Gy (range 3–48), delivered in five fractions (range 1–16) on 17 days (range 1–77). Eight patients received 3D-conformal and 13 received 2D-conformal radiotherapy. Clinical target volumes included the parotids and submandibular glands (18 patients), submandibular glands and one parotid (one patient), or parotids (two patients). Thirteen patients were treated with 5.5–6 MV photons and eight were treated with 6–15 MeV electrons. A satisfactory salivary response was defined as complete or partial improvement. The median follow up was 10.4 months (range 0.4–26). One patient was lost to follow up.ResultsA positive response was observed in 65% of patients during a mean of 7 months (range 1–23). Four patients (20%) treated with photons and no patients treated with electrons experienced acute toxicity. Half (50%) the patients treated with photons and 87.5% of patients treated with electrons responded positively (P = 0.09). Positive responses were more common with a high total dose (≥ 16 Gy; 78.6%) than a low total dose (< 16 Gy; 33%; P = 0.07). No differences were observed in tolerance (P = 0.27). Age and sex did not impact the response.ConclusionSalivary gland radiotherapy effectively reduced sialorrhea in patients with amyotrophic lateral sclerosis. An adequate compromise between toxicity and efficiency was achieved with 3D-conformal radiotherapy delivered with electrons to parotids and submandibular glands in a total dose of 16 Gy or more (mean: 20 Gy in five fractions).     

Primary bone lymphoma--treatment and outcome

AimsA retrospective review of patients with histologically confirmed primary bone lymphoma (PBL) diagnosed and treated at a single tertiary referral centre between 1985 and 2003.Materials and methodsThe medical records of all patients treated for histologically primary bone lymphoma were identified using the hospital data base. Data was obtained on patient demographics, stage, treatment and outcome.ResultsTwenty-two patients with PBL were identified. Seventeen had localised disease and five had multifocal bone involvement. The median age was 50 years. Of the patients who could be graded according to the International Prognostic Index (IPI), 12 cases were classified as low risk, seven as intermediate risk and one as high risk. All patients received chemotherapy; 19 with an anthracycline-containing regimen. Eighteen patients were treated with radiotherapy to a median total dose of 40 Gy (range 30–50 Gy). Three patients had surgery instead of radiotherapy as local treatment (one fibulectomy and two endoprosthetic replacements). The median follow-up was 84.5 months (range 3–206 months). The overall 10-year survival was 74%; 92% for low-risk IPI vs 73% for intermediate-risk IPI (P = 0.27). The 10-year relapse-free survival was 85% overall and 83% for both low- and intermediate-risk IPI (P = 0.87). Local relapse was seen in one patient. Orthopaedic complications occurred in two patients — one developed a pathological fracture after biopsy before radiotherapy and the other developed avascular necrosis outside the irradiated area.ConclusionsCombined modality treatment for PBL results in good local control and survival rates with acceptable toxicity.     

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study

AimsProton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT.Materials and methodsChildren younger than 2 years of age treated with PBT for central nervous system tumours enrolled in the prospective registry study KiProReg were retrospectively analysed. Information on patient characteristics, treatment, toxicities and outcome were evaluated. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE V4.0) before, during and after PBT.ResultsBetween September 2013 and June 2018, 51 infants were eligible. The median age was 19 months (range 11–23 months) at the time of PBT. Tumour entities were ependymoma (51.0%), atypical teratoid rhabdoid tumour (39.0%), high-grade glioma (6.0%), pineoblastoma (2.0%) and medulloblastoma (2.0%). The prescribed median total dose was 54.0 Gy (range 45.0–59.4 Gy). Most received local radiotherapy. In four patients, craniospinal irradiation followed by a boost to the local tumour bed was applied. The median follow-up time was 42.0 months (range 7.3–86.2 months). The estimated 3-year local control, progression-free survival and overall survival rates for all patients were 62.7, 47.1 and 76.5%, respectively. During radiotherapy, 24 events of higher-grade (CTCAE ≥ °III) toxicities were reported. Interruption of radiotherapy for more than 2 days was due to infection (n = 3) or shunt complication (n = 2). Unexpected hospitalisation during radiotherapy affected 12 patients. Late adverse events attributable to radiotherapy included endocrinopathy (CTCAE °II; 7.8%), new onset of hearing loss (CTCAE °III; 5.8%) and visual impairment (CTCAE °IV; 1.9%). Transient radiation-induced imaging changes occurred in five patients (9.8%).ConclusionsOur study indicates that PBT is feasible for very young children with central nervous system tumours, at least in the short term. However, it requires challenging interdisciplinary medical care and high logistical effort. For evaluation of late effects, longer follow-up and evaluation of neurocognitive outcome are desirable. More data have to be gathered to further define the role of radiotherapy in infants over time.     

Can Dose Reduction to One Parotid Gland Prevent Xerostomia? — A Feasibility Study for Locally Advanced Head and Neck Cancer Patients Treated with Intensity-modulated Radiotherapy

AimsDryness of the mouth is one of the most distressing chronic toxicities of radiation therapy in head and neck cancers. In this study, parotid function was assessed in patients with locally advanced head and neck cancers undergoing intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Parotid function was assessed with the help of a questionnaire and parotid scintigraphy, especially with regards to unilateral sparing of the parotid gland.Materials and methodsIn total, 19 patients were treated with compensator-based IMRT between February 2003 and March 2004. The dose to the clinical target volume ranged between 66 and 70 Gy in 30–35 fractions to 95% of the isodose volume. Ipsilateral high-risk neck nodes received an average dose of 60 Gy and the contralateral low-risk neck received a dose of 54–56 Gy. Eight of 19 patients also received concomitant chemotherapy.ResultsSubjective toxicity to the parotid glands was assessed with the help of a questionnaire at 0, 3 and 6 months and objective toxicity was assessed with parotid scintigraphy at 0 and 3 months. The mean dose to the ipsilateral parotid gland ranged from 19.5 to 52.8 Gy (mean 33.14 Gy) and the mean dose to the contralateral gland was 11.1–46.6 Gy (mean 26.85 Gy). At a median follow-up of 13 months, 9/19 patients had no symptoms of dryness of the mouth (grade I), 8/19 had mild dryness of the mouth (grade II) and only 2/19 had grade III xerostomia, although the parotid gland could only be spared on one side in most of the patients.ConclusionsMinimising the radiation dose to one of the parotid glands with the help of IMRT in patients with advanced head and neck cancers can prevent xerostomia in most patients and parotid scintigraphy is a useful method of documenting xerostomia.     

Accelerated Hypofractionated Radiotherapy for Centrally Located Lung Tumours Not Suitable for Stereotactic Body Radiotherapy or Chemoradiotherapy

AimsAccelerated hypofractionated radiotherapy is used at our institution for non-small cell lung cancer (NSCLC) patients not eligible for stereotactic body radiotherapy or chemoradiotherapy. The purpose of this study was to report clinical outcomes of delivering 60 Gy in 15 fractions for these patients.Materials and MethodsAll NSCLC patients who received 60 Gy in 15 fractions were reviewed. Outcomes of interest were local failure, regional failure, distant progression, overall survival and treatment-associated toxicities.ResultsIn total, 111 patients were included. The median age was 78.8 years and most tumours were adenocarcinoma (n = 55, 49.6%). Sixty-five patients (58.6%) were N0. The cumulative incidence of local failure at 12 and 24 months in the N0 cohort was 5.2% and 14.2%, respectively, compared with 11.5% and 14.8% for N+ patients. Tumour size >35 mm predicted for local failure (hazard ratio 2.706, 95% confidence interval 1.002–7.307, P = 0.0494). Distant progression at 12 and 24 months in N0 patients was 13.7% and 24.3% compared with 24.6% and 33.5% in N+ patients. In N0 patients, larger tumour size was associated with increased risk of distant progression. The median overall survival was 38.1 months in N0 patients versus 31.7 months in N+ patients. The most common toxicity was radiation pneumonitis (n = 6, 6.4%). The incidence of any grade 3 toxicity was 10.3% at ≥1 year. There were no deaths or hospitalisations attributed to treatment.ConclusionsAccelerated hypofractionated radiotherapy is well tolerated and resulted in favourable clinical outcomes in various stages of NSCLC patients.     

Analysis of Radiotherapy in 1054 Patients with Primary Central Nervous System Lymphoma Treated from 1985 to 2009

AimsData on primary central nervous system lymphoma that had been collected through surveys for four consecutive periods between 1985 and 2009 were analysed to evaluate outcomes according to treatment.Materials and methodsAll had histologically proven disease and had received radiotherapy. No patients had AIDS. Among 1054 patients, 696 died and 358 were alive or lost to follow-up. The median follow-up period for surviving patients was 37 months.ResultsFor all patients, the median survival time was 24 months; the 5 year survival rate was 25.8%. Patients treated with methotrexate-based chemotherapy and radiation had a higher 5 year survival rate (43%) than those treated with radiation alone (14%) and those treated with non-methotrexate chemotherapy plus radiation (20%), but differences in relapse-free survival were smaller among the three groups. The 5 year survival rate was 25% for patients treated with whole-brain irradiation and 29% for patients treated with partial-brain irradiation (P = 0.80). Patients receiving a total dose of 40–49.9 Gy had a higher 5 year survival rate (32%) than those receiving other doses (21–25%, P = 0.0004) and patients receiving a whole-brain dose of 30–39.9 Gy had a higher 5 year survival rate (32%) than those receiving ≥40 Gy (13–22%, P < 0.0005). Patients receiving methotrexate-based chemotherapy and partial-brain radiotherapy (≥30 Gy) had a 5 year survival rate of 49%.ConclusionsThe optimal total and whole-brain doses may be in the range of 40–49.9 and <40 Gy, respectively, especially in combination with chemotherapy. Patients receiving partial-brain irradiation had a prognosis similar to that of those receiving whole-brain irradiation. With methotrexate-based chemotherapy, partial-brain radiotherapy may be worth considering for non-elderly patients with a single tumour.     

Dosimetric Comparison Between Helical Tomotherapy and Volumetric Modulated Arc Therapy in Patients With Malignant Pleural Mesothelioma

AimsTo carry out a dosimetric comparison and constraints feasibility proof of adjuvant radiotherapy through helical tomotherapy or volumetric modulated arc therapy (VMAT) for malignant pleural mesothelioma patients after pleurectomy/decortication.Materials and methodsRetrospective calculations were carried out on previously acquired simulations. A whole-pleura volume with 50.4 Gy in 28 fractions was prescribed, simulating a no residual tumour situation. Calculations were carried out using an anisotropic analytical algorithm with a 2.0 mm grid. Beam-on time, planning target volume (PTV) coverage, homogeneity index and organ at risk exposure were compared.ResultsSixteen patient plans were calculated per device. Constraints were met overall by both modalities. For helical tomotherapy and VMAT plans, median beam-on times were 13.8 (11.6–16.1) min and 6.4 (6.1–7.0) min; P = 0.006. The median left-sided radiotherapy PTV D₉₈ were 48.1 (48.0–48.8) Gy and 47.6 (46.5–48.3) Gy; P = 0.023. No significant difference for right-sided radiotherapy was found. PTV D₂ for left-sided radiotherapy was higher with VMAT (P = 0.014). For right-sided radiotherapy, helical tomotherapy showed higher doses (P = 0.039). No homogeneity index differences for left-sided radiotherapy (P = 1.00) and right-sided radiotherapy (P = 0.598) were seen. Significant organ at risk exposure differences were found on left-sided radiotherapy whole-lung V_20, as well as D₅₀ (both P = 0.008). Higher contralateral lung and ipsilateral kidney exposures were found with VMAT plans for both treatment sides.ConclusionAdjuvant radiotherapy after pleurectomy/decortication in malignant pleural mesothelioma patients, with a VMAT- or helical tomotherapy-based platform, is dosimetrically feasible. Lung sparing was mostly improved with helical tomotherapy. Technique selection must be carried out according to availability and clinical criteria.     

Locoregional control and toxicity following high-dose hypofractionated and accelerated palliative radiotherapy regimens in breast cancer

AimsFor patients with locally advanced primary/recurrent breast cancer, radiotherapy is an effective treatment for locoregional control. 36 Gy in 6 Gy once-weekly fractions is a commonly used schedule, but there are no data comparing local control and toxicity between 36 Gy delivered once-weekly versus accelerated schedules of multiple 6 Gy fractions per week. This retrospective study compared local control rates and acute and late toxicity in patients undergoing 30–36 Gy in 6 Gy fractions over 6 weeks versus more accelerated schedules over 2–3 weeks for an unresected breast cancer.Materials and methodsPatients who received 30–36 Gy in 6 Gy fractions to an unresected breast cancer ± involved lymph nodes between December 2011 and August 2020 were identified. Patients were grouped into once-weekly versus accelerated fractionation schedules. Response rates, local control and toxicity data were analysed.ResultsIn total, 109 patients were identified. The median follow-up duration was 46 months. Forty-seven patients (43%) received once-weekly fractions and 62 patients (57%) received accelerated fractionation schedules. There were no significant differences in baseline tumour characteristics between the groups. Eighty-seven per cent of patients had an objective (complete or partial) response (81% in the once-weekly group; 91% in the accelerated group). The median time to local progression was 23.5 months overall (95% confidence interval 17.8–29.2); 23.5 months (95% confidence interval 18.8–28.1) in the once-weekly group and 19.0 months (95% confidence interval 7.0–31.1) in the accelerated group (P = 0.99). Acute toxicity of any grade occurred in 75% of patients (76% in the once-weekly group; 74% in the accelerated group) and grade 3 toxicity occurred in 7% of patients (7% in the once-weekly group; 8% in the accelerated group). There were no associations between the groups and acute or late toxicity grade (P = 0.78 and P = 0.26, respectively), although one grade 4 late toxicity (skin radionecrosis) occurred in a patient who received five fractions a week and therefore this regimen is not recommended. Study limitations included a lack of statistical power analysis, the necessary grouping of all accelerated patients for analysis and a high rate of censored data.ConclusionThere were no apparent differences in response rate, time to local progression or toxicity between patients who received 30–36 Gy in 6 Gy fractions once-weekly compared with twice-weekly as palliative treatment for locally advanced breast cancer. This regimen appears to be a safe alternative and may be preferred by patients.     

Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated Patients Affected by Recurrent Prostate Cancer

AimsRobotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife.Materials and methodsData from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03.ResultsAll patients received prior EBRT. The median EQD2 total dose was 74 Gy (60–80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of –77.1% (14.3–99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0–2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity.ConclusionFocal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control.     

Is dose de-escalation possible in sarcoma patients treated with enlarged limb sparing resection?

PurposeTo evaluate the impact of dose de-escalation in a large series of resected limbs soft tissue sarcomas (STS).MethodsData were retrospectively analysed from 414 consecutive patients treated for limb STS by enlarged surgery and radiotherapy at Gustave Roussy from 05/1993 to 05/2012. Radiotherapy (RT) dose level was decided by the multidisciplinary staff and depended upon the quality of surgery and margins size.ResultsRT was delivered prior (13%) or after (87%) surgery. Seven patients (2%) had pre- and a postoperative RT boost. Median delivered RT dose was 50 Gy (36–70 Gy), and 33% received ≥55 Gy. At a median follow-up of 6.8 years, the 5-year actuarial local relapse (LR) rate was 7% (95% CI: 4.4–10%). The median time to the first LR was 2.7 years (range: 0.6–11.2 years). The LR was most often located within the irradiated field (26/32; 81%), where the median total applied dose was 56 Gy (range, 40–60 Gy). The 5-year LR rates were 4%, and 15% in patients receiving <55 Gy, and in those who had ≥55 Gy (p < 0.001), respectively. In the multivariate analysis, dose ≥55 Gy (HR [hazard ratio]: 2.9; p = 0.02), certain histological subtypes (HR: 7.8; p < 0.001), and minimal surgical margins <1 mm (HR: 2.9; p = 0.02) were associated to higher LR rates. In the subgroup of patients with “positive” margins <1 mm (n = 102), these histological subtypes (HR: 4.4; p = 0.03), and inadequate initial surgery justifying re-excision (HR: 3; p = 0.048) predicted for an increased LR, whereas dose of irradiation did not (p = 0.2). Patients who had late complications (n = 64; 15%) received higher doses of irradiation as compared with other patients (median: 55 Gy vs. 50 Gy, respectively; p < 0.001).ConclusionIn this retrospective analysis of patients having enlarged surgery and RT, histological subtype is the strongest predictor of LR, whereas dose de-escalation did not lead to worse outcomes. A dose of 50 Gy may be recommended in case of planned enlarged surgery with R0 margins.     

Compensator-based intensity-modulated radiotherapy in head and neck cancer: our experience in achieving dosimetric parameters and their clinical correlation

AimsTo review the Batra Hospital and Medical Research Centre experience of using compensator-based intensity-modulated radiotherapy (IMRT) to treat head and neck cancer.Materials and methodsBetween October 2003 and August 2004, 18 patients underwent IMRT for head and neck cancer at our institution. IMRT was delivered using partial transmission high-resolution compensator blocks.ResultsWith a median follow-up of 13.3 months, two patients had residual disease and two failed in the gross tumour volume (GTV). The complete response rate after surgical salvage was 94.5%. Both the locoregional relapse-free and disease-free survival rates were 81.8%. The target coverage in terms of average maximum, mean and minimum dose (in Gy) delivered was 78.6, 73.5 and 58.4 to the GTV–planning target volume, 82.3, 70.9 and 47.3 to clinical target volume 1 (CTV1) and 82.9, 66.2 and 29.6 to CTV2. The dose constraint of 30 Gy to less than 50% of the contralateral parotid volume was achieved in 12 (66.7%) patients. If the dose constraint was revised to 35 Gy, at least 50% of the parotid volume was spared in 17 (94.5%) patients. On average, 75% of the contralateral parotid volume received a dose less than 35 Gy in 13 (72.3%) patients with grade I xerostomia, whereas this was 49.3% in five (27.7%) patients with grade II xerostomia, and the difference was statistically significant (P = 0.001).ConclusionsIn our initial experience, compensator-based IMRT is feasible with regard to target coverage and parotid volume sparing. The parotid volume dose has significant clinical implications on the grade of xerostomia. Our results invoke rethinking into the issues of the parotid volume dose constraint in our subpopulation.     

A prospective study of pulmonary function in Hodgkin’s lymphoma patients

BackgroundTo prospectively study changes in lung function in Hodgkin's lymphoma (HL) patients and to explore predictors for these changes over time.MethodsIn all, 52 patients with HL receiving bleomycin-based chemotherapy with (n = 23) or without (n = 29) mediastinal radiotherapy were enrolled. Pretreatment pulmonary function tests were carried out. These were repeated at 1 month, 6 months, and 1 year after therapy.ResultsWith chemotherapy alone, the median %DLCO declined significantly at 1 month but returned to baseline by 6 months. The median %DLCO did not further decrease with radiotherapy, but remained persistently reduced at 1 year. In patients who received radiotherapy, having >33% of lung volume receive 20 Gy (V20) and a mean lung dose (MLD) of >13 Gy significantly predicted for persistently reduced %DLCO at 6 months (P = 0.035). Smoking significantly predicted for a persistently reduced %DLCO at 1 year (P = 0.036). On multivariable analysis, significant predictors for decline in %DLCO at 1 year were higher baseline %DLCO (P = 0.01), higher MLD (P = 0.02), and a smoking history (P = 0.02).ConclusionsSeveral factors contribute to decline in %DLCO in HL patients who received bleomycin-based computed tomography. The identification of threshold radiation dosimetric parameters for reduced lung function may provide guidance in the radiation planning of these patients.     

Tumeurs spinales et paraspinales traitées par irradiation stéréotaxique par CyberKnife® au centre Antoine-Lacassagne de Nice

PurposeStereotactic radiotherapy using the CyberKnife^® has become a key treatment in the multidisciplinary management of secondary tumours, as well as primary benign or malignant tumours located within or adjacent to vertebral bodies and the spinal cord. The aim of this treatment is to improve local control and clinical response, including previously irradiated cases.Patients and methodsIn this study, we present the first patients treated with CyberKnife^® between December 2006 and December 2007 for spinal or paraspinal tumours. The primary aim was to assess the feasibility and tolerance of stereotactic radiotherapy using the CyberKnife^®. Secondary aims were to establish the short-term local control, to calculate the local progression-free survival and overall survival. Clinical examination and imaging procedures were performed every three months. Response was assessed according to RECIST criteria.ResultsDuring that period, 16 patients were treated with CyberKnife^®. Thirteen patients had been pre-treated, three of whom had received spinal cord doses considered to be maximal. Three patients did not receive previous irradiation. The median age was 59 (36–74). The most frequent symptoms were pain (n = 8) and motor weakness (n = 4). The median dose was 30 Gy (16–50). The median number of fractions was 3 (1–5). No patient developed acute myelitis. Three patients developed acute reaction. Overall survival at 18 months was 72.4%, with a mean survival of 18.2 months (95% CI: 15.4–20.9). Local progression-free survival at 18 months was 58.4%, with a mean value of 16.9 months (95% CI: 13.6–20.2).ConclusionThe use of stereotactic radiotherapy with CyberKnife^® represents a major progress in the management of paraspinal tumours. The main advantages are better sparing of the spinal cord and the possibility of increasing the dose to the tumour target volume.     

Results of external-beam radiotherapy alone in invasive cancer of the uterine cervix: a retrospective analysis

AimsIn this retrospective audit, we describe the results of external-beam radiotherapy (EBRT) alone in patients with invasive cancer of the cervix treated at our centre.Material and MethodsWe included 146 patients with invasive cancer of the cervix who were treated with EBRT to a total dose of 60–66 Gy between January 1996 and December 2001. None of these patients were suitable for intracavitary radiotherapy (ICRT) after a median dose of 46 Gy. A boost dose of 14–20 Gy was given after a gap of 2–4 weeks. Most patients belonged to stage IIIB (n = 124).ResultsFollow-up of patients at risk ranged from 19 to 89 months (median 48 months). One hundred and thirty-six patients (93.2%) received EBRT to a dose of 66 Gy, and 10 patients (6.8%) received 60 Gy. Overall treatment time (OTT) ranged from 56 to 160 days (median 78 days). At completion of 46 Gy of EBRT, 63 patients achieved partial response and 83 patients had stable disease. Five-year overall survival, disease-free survival (DFS) and pelvic control were 15.1% (median 9 months), 11.6% (median 5 months) and 21.9% (median 6 months), respectively. Factors found to affect 5-year pelvic control in univariate analysis by Kaplan–Meier method were response to EBRT at 46 Gy (partial response 36.5% and stable disease 10.8%), age (≥50 years 28.8% and <50 years 13.6%) and OTT (<90 days 26.5% and ≥90 days 12.5%). For DFS and overall survival, response to EBRT was the only factor that was significant in univariate analysis. In multivariate analysis by Cox's proportional hazard model, response to EBRT was the only factor to influence pelvic control (P = 0.007), DFS (P = 0.01) and overall survival (P < 0.001).ConclusionsOverall outcome of patients in whom ICRT was not given remains less than satisfactory. Response to EBRT emerged as the most important factor to predict all clinical outcomes. To improve upon the dismal results of EBRT alone, we will have to decrease the OTT and consider concurrent chemo-radiation with cisplatin.