M. Ketelaars

Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy.

OBJECTIVEnSince the Group Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO) published recommendations for 3D MRI-based image-guided adaptive brachytherapy (IGBT) in the treatment of cervical cancer, many institutions have implemented this technique and favourable results were documented. We investigated if introduction of IGBT in our centre indeed improved treatment outcomes and reduced toxicity compared to conventional brachytherapy (CBT).nnnMETHODSnA retrospective analysis was done of outcomes of patients with stage IB-IVA cervical cancer treated with primary radiation therapy with curative intent between 2000 and 2012. Outcome measures were overall and disease-free survival, pelvic control, distant metastasis and treatment related adverse events (AE).nnnRESULTSn126 patients were analysed; 43 had been treated with CBT between 2000-2007, and 83 with IGBT between 2007-2012. External beam radiation (mean; 46.6Gy) was combined with concurrent weekly cisplatin (51.6%), or hyperthermia (24.6%); radiation alone was used in 23.8%. Median follow-up was 121.8months for CBT patients, vs. 42.3months for IGBT. Complete remission was achieved in 83.7% of patients in the CBT group and in 98.8% of IGBT patients (p<0.01). Overall survival at 3years was 51% and 86%, respectively (p=0.001). Pelvic recurrence was found in 32% vs. 7% (p<0.001). Most patients had low grade adverse events. High grade (3-4) AE occurred in 15.4% vs. 8.4% at 3years (p=0.06).nnnCONCLUSIONnIntroduction of IGBT for cervical cancer has led to significantly increased 3-year locoregional control and survival rates, whilst reducing late morbidity.

Long-term outcomes of eye-conserving treatment with Ruthenium106 brachytherapy for choroidal melanoma ☆

PURPOSEnTo evaluate long-term outcomes of eye-conserving treatment using Ruthenium-106 plaque brachytherapy with or without transpupillary thermotherapy (TTT) for small to intermediate size choroidal melanomas.nnnMETHODSnOutcomes of 425 consecutive patients were analysed. The median basal tumour diameter was 10.9 mm (range 4.8-15.9 mm), and the median apical height 4.2 mm (range 1.2-9.3 mm). Brachytherapy doses ranged from 400 to 600Gy with TTT (86%), or from 600 to 800Gy without TTT (14%), specified at the scleral surface. Kaplan-Meier survival curves, log-rank tests and Cox regression analysis were used for analysis.nnnRESULTSnMedian follow-up was 50 months. Five-year actuarial local control was 96%. Five-year overall and metastases-free survival rates were 79.6% and 76.5%. Prognostic factors for metastasis-free survival were peripheral location (p=0.02) and smaller basal diameter (p<0.001). No dose effect relationships were found. Radiation side effects were frequent, with 2- and 5-year rates free of radiation complications of 60% and 35%. Five-year enucleation rate was 4.4% (10 for local recurrence, 7 for complications). Cosmetic and functional (visual acuity >0.10) eye preservation rates were 96% and 52% at 5 years.nnnCONCLUSIONSnRuthenium-106 brachytherapy for choroidal melanoma provides excellent rates of local control and eye preservation.

Ruthenium plaque radiation therapy for iris and iridociliary melanomas

Purpose:u2002 To determine the long‐term effects of ruthenium‐106 plaque radiation therapy for iris and iridociliary melanomas in terms of tumour regression and complications.

Endorectal Brachytherapy Boost After External Beam Radiation Therapy in Elderly or Medically Inoperable Patients With Rectal Cancer: Primary Outcomes of the Phase 1 HERBERT Study

PURPOSEnTo evaluate the toxicity and efficacy of the combination of external beam radiation therapy (EBRT) followed by high-dose-rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer.nnnMETHODS AND MATERIALSnA phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13xa0×xa03xa0Gy) followed by 3 weekly brachytherapy applications 6xa0weeks later. The HDREBT dose started at 5xa0Gy per fraction, increasing with 1xa0Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis <6xa0weeks after HDREBT) occurred in ≤2 patients per dose level. The primary endpoint was the maximum tolerated dose, defined as 1 dose level below the dose at which 3 patients experienced DLT. Secondary endpoints were toxicity, clinical tumor response, freedom from local progression, and local progression-free and overall survival (L-PFS and OS).nnnRESULTSnThirty-eight patients with a median age of 83xa0years were included in the study. Thirty-two were evaluable for DLT and late toxicity and 33 for response evaluation. Maximum delivered dose was 8xa0Gy per fraction, resulting in a recommended dose of 7xa0Gy per fraction. Response occurred in 29 of 33 patients (87.9%), with 60.6% complete response (CR). The L-PFS and OS rates were 42% and 63%, respectively, at 2xa0years. Patients with CR showed a significantly improved L-PFS (60% at 2xa0years, P=.006) and a trend in improved OS (80% at 2xa0years, P=.11). Severe late toxicity occurred in 10 of 32 patients.nnnCONCLUSIONnWe found that HDREBT after EBRT results in a high overall response rate, with improved L-PFS for patients with a CR. The high observed rate of severe late toxicity requires further evaluation of the risks and benefits of an HDREBT boost.

Ruthenium-106 brachytherapy for choroidal melanoma without transpupillary thermotherapy: Similar efficacy with improved visual outcome

PURPOSEnTo evaluate efficacy and toxicity of two different protocols for eye-conserving treatment of patients with small to intermediate-sized choroidal melanomas; the current ruthenium-106 (Ru106) brachytherapy protocol and the preceding protocol of Ru106-brachytherapy with transpupillary thermotherapy (Ru106/TTT).nnnMETHODS AND MATERIALSnLong-term outcomes of 449 consecutive patients, of whom 196 (43.6%) treated using Ru106/TTT and 253 (56.3%) treated using Ru106, were compared in terms of local control, survival, eye preservation and visual outcome.nnnRESULTSnMedian follow-up was 82.8 months. Patients in the Ru106-group had smaller, less centrally located tumours and better pre-treatment visual acuity (VA). Five-year cumulative incidence of local failure was 11.2% for Ru106/TTT and 5.2% for Ru106, which was not statistically significant after correction for differences in baseline characteristics (hazard ratio for Ru106xa0=xa00.57, pxa0=xa00.14). Cumulative incidence of distant metastases was 11.2xa0versus 6.2%, and cumulative incidence of cause-specific death was 22.4xa0versus 5.5% for Ru106/TTT and Ru106 respectively. Enucleation was performed in 9.2xa0versusxa04.0% for Ru106/TTT versus Ru106; 5.1xa0versus 3.2% for local failure and 2.6xa0versus 0.8% for complications. At one year of follow-up, significantly more patients had lost useful vision (VAxa0<xa00.33) in the Ru106/TTT-group than in the Ru106-group (50.0xa0versus 24.5%). After two and three years, the differences decreased (54.6xa0versus 34.0% and 61.7xa0versus 45.8%, respectively) and lost statistical significance.nnnCONCLUSIONSnBoth the current Ru106 and the preceding Ru106/TTT-protocols provided excellent tumour control, cosmetic and functional eye preservation and vital prognosis. The Ru106-protocol yielded prolonged preservation of VA and should be regarded the current standard of treatment.

Benefit of adaptive CT-based treatment planning in high-dose-rate endorectal brachytherapy for rectal cancer

PURPOSEnIn this planning study, we investigated the dosimetric benefit of repeat CT-based treatment planning at each fraction vs. the use of a single CT-based treatment plan for all fractions for high-dose-rate endorectal brachytherapy (HDREBT) for rectal cancer.nnnMETHODS AND MATERIALSnWe included 11 patients that received a CT scan with applicator in situ for all three fractions. The treatment plan of the first fraction was projected on the repeat CT scans to simulate the use of a single treatment plan. In addition, replanning was performed on the repeat CT scans, and these were compared to the corresponding projected treatment plans.nnnRESULTSnRepeat CT-based treatment planning resulted on average in a 21% higher (pxa0= 0.01) conformity index compared to single CT-based treatment planning. Projecting the initial treatment plan to the repeat CT scans of fraction two and three, 12/22 fractions reached a CTV D98 of 85% of the prescribed dose of 7xa0Gy, which increased to 14/22 using replanning. For the remaining fractions, median CTV D98 was 4.2xa0Gy, and an intervention would be necessary to correct applicator balloon setup or to remove remaining air and/or feces between the CTV and the applicator.nnnCONCLUSIONSnUsing a single CT-based treatment plan for all fractions may result in a suboptimal treatment at later fractions. Therefore, repeat CT imaging should be the minimal standard practice in HDREBT for rectal cancer to determine whether an intervention would be necessary. Replanning based on repeat CT imaging resulted in more conformal treatment plans and is therefore recommended.

Ruthenium-106 brachytherapy for iris and iridociliary melanomas

Background and purpose To evaluate ruthenium-106 (Ru106) brachytherapy as eye-conserving treatment of iris melanomas (IMs) and iridociliary melanomas (ICMs). Materials and methods Eighty-eight patients received Ru106 brachytherapy between 2006 and 2016. Primary outcome was local control, and secondary outcomes were metastasis, survival, eye preservation, complications and visual acuity (VA). Results Overall median follow-up was 36 months. Of 88 patients, 58 (65.9%) had IM and 30 (34.1%) had ICM. ICM were on average larger and more advanced than IM. Local failure-free survival at 3years was 98.9% (SE 1.2%). Metastasis-free survival was 98.2% (SE 1.8%) at 3years; no deaths due to melanoma occurred during follow-up. Eye preservation rate was 97.7%. Treatment-related toxicities were mostly mild and observed in 80.7% of the patients. Common toxicities were worsening of pre-existing or new cataract (51.1%), dry eyes (29.5%) and glaucoma (20.5%). VA was not affected by Ru106 brachytherapy, with only 2.3% having VA <0.33 (low vision) at follow-up. Conclusions Ru106 for IM and ICM yielded excellent local control (98.9%) and eye preservation (97.7%). Toxicities were common, but mostly mild and transient. Moreover, Ru106 did not affect visual acuity.