Impact of PTV margin reduction (2 mm to 0 mm) on pseudoprogression in stereotactic radiotherapy of solitary brain metastases.

PURPOSE: To determine the influence of PTV-margin (0 mm versus 2 mm) on the incidence of pseudoprogression (PP) and local tumour control (LC) in patients treated with stereotactic radiotherapy (SRT) for solitary brain metastases. METHODS: Patients were treated on Novalis LINAC. Three dose schedules were used depending on the PTV-size. The PTV-margin was 2-mm prior to 2015 and 0-mm thereafter. MRI-scans were made every three months including a perfusion MRI-scan when pseudoprogression was suspected. We examined the relation of pseudoprogression and local control with the size of PTV-margin. Besides this, the association of dose-volume data of the whole brain (minus GTV) and pseudoprogression was investigated. RESULTS: 121 patients were analyzed (2-mm margin in 84 patients; 0-mm margin in 37 patients). There was no difference in GTV (7.6 cc versus 9.1 cc p = 0.2). At 24 months there was no difference in incidence of pseudoprogression (49% and versus 33%, p = 0.5) and local control in the 2-mm and 0-mm group (82% and versus 79%, p = 1.0). The size of PTV-margin was not associated with PP. Both margin and volume of brain receiving 12 Gy (V12) were not associated with pseudoprogression in patients treated with single fraction. CONCLUSIONS: PTV-margin reduction did not reduce the incidence of pseudoprogression in LINAC-based-SRT for single brain metastases. We did not find a significant association of GTV-PTV margin or V12Gy with the incidence of pseudoprogression in solitary metastases treated with a single fraction. LC rates were similar, indicating margin reduction seems to be safe.

Relative influence of watershed and geomorphic features on nutrient and carbon fluxes in a pristine and moderately urbanized stream.

Streams are important sites of elemental transformations due to the relatively high contact rates between flowing water and biogeochemically reactive sediments. Increased urbanization typically results in higher nutrient and carbon (C) inputs to streams from their watersheds and increased flow rates due to modification in channel form, reducing within stream net retention and increasing downstream exports. However, less is known on how moderate urbanization might influence the joint processing of C, nitrogen (N), and phosphorus (P) in streams or the relative influence of changes in watershed and stream features on their fluxes. In this study, we performed mass-balances of different C, N, and P species in multiple reaches with contrasting land use land cover and geomorphic features (pools, riffles, runs) to determine the effects of geomorphology versus human influence on elemental fluxes in a pristine and a semi-urban stream. N was the most responsive of all elements, where nitrate concentrations were 3.5-fold higher in the peri-urban stream. Dissolved organic carbon was only slightly higher in the peri-urban site whereas total P not significantly different between streams. In terms of fluxes, nitrate behaved differently between the streams with net retention occurring in the majority of the reaches of the pristine site, whereas net export was observed in all of the reaches of the semi-urban one. We found a decrease in nitrate concentrations with an increase in excess deuterium of the water (d-excess), an indicator of how overall water retention capacity of the watershed favored N loss. Within the stream, the presence of pools, and reduced channel slope, which also increase water retention time, again favored N loss. Overall, nitrate was the most sensitive nutrient to slight urbanization, where higher export to stream was influenced by land use, but where geomorphic features were more important in driving retention capacity.

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.

PURPOSE: To 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. METHODS AND MATERIALS: A phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13 × 3 Gy) followed by 3 weekly brachytherapy applications 6 weeks later. The HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis <6 weeks 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). RESULTS: Thirty-eight patients with a median age of 83 years were included in the study. Thirty-two were evaluable for DLT and late toxicity and 33 for response evaluation. Maximum delivered dose was 8 Gy per fraction, resulting in a recommended dose of 7 Gy 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 2 years. Patients with CR showed a significantly improved L-PFS (60% at 2 years, P=.006) and a trend in improved OS (80% at 2 years, P=.11). Severe late toxicity occurred in 10 of 32 patients. CONCLUSION: We 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.

Single dose IOERT versus whole breast irradiation : Cosmetic results in breast-conserving therapy.

BACKGROUND: Scarce data are available about the cosmetic result of single dose intraoperative electron radiotherapy (IOERT) in breast-conserving radiotherapy. METHODS AND MATERIALS: We included 71 breast cancer patients. Breast-conserving surgery and sentinel node procedure had started almost 3 years earlier. Subsequently, 26 patients were treated with IOERT and 45 patients received postoperative whole breast irradiation (WBI). For both groups we determined seven dimensionless asymmetry features. We compared the subjectively and the objectively derived cosmetic scores with each other. RESULTS: For four asymmetry features we noted significantly smaller differences for patients treated with IOERT when compared to those treated with WBI: relative breast contour difference, relative breast area difference and relative breast overlap difference. After correcting for excision volume a significant difference was noticed also for relative lower breast contour. For the IOERT group the cosmetic scores "excellent or good" as determined by each patient and one physician were 88 and 96 %, respectively. When the overall cosmetic scores for patients treated with IOERT and WBI were compared to those of the objectively derived scores, there was a fair level of agreement. CONCLUSION: For patients treated with IOERT we noted less asymmetry and high rates of "good or excellent" subjectively derived cosmetic scores. The level of agreement between the subjectively and the objectively derived cosmetic scores was limited. Due to the small sample size and the design of the study no definitive conclusions can be drawn.

Radical radiotherapy compared with surgery for advanced squamous cell carcinoma of the base of tongue.

PURPOSE: This study reports on T3/T4 base of tongue (BOT) tumors treated at the Erasmus MC (Rotterdam) with external beam radiotherapy (EBRT) and brachytherapy (BT). Local control, survival, and functional outcome are compared to results obtained in similar patients treated at the Vrije University Medical Center (VUMC, Amsterdam) by surgery and postoperative RT (PORT). METHODS AND MATERIALS: At Rotterdam 46/2 Gy was given to the primary and bilateral neck, followed by an implant using low-dose-rate (LDR 24-35 Gy; median 27 Gy), or fractionated high-dose-rate (fr. HDR 20-28 Gy; median 24 Gy). A neck dissection (ND) was performed in case of N+ disease. 67% of BOT tumors had a T4 cancer. At Amsterdam surgery (S) followed by PORT 40-70 Gy (median 60 Gy) was performed; 26% BOT tumors were T4. Sex, age and nodal distribution were similar. Actuarial local control and survival were computed. Performance Status Scale (PSS) scores were established. Xerostomis was determined on visual analog scales (VAS). RESULTS: Local failure at 5-years was 37% (Rotterdam) vs. 9% (Amsterdam) (p < 0.01). The overall survival was not significantly different (median 2.5 years vs. 2.9 years, respectively [p = 0.47]). The PSS favored brachytherapy. Both groups were equally affected by xerostomia. CONCLUSIONS: The 5-year local control was 65% with EBRT and BT. This result is strongly affected by 4 patients with residual disease after implantation. The Rotterdam patients had more advanced BOT tumors (67% vs. 26% T4), explaining the higher local failure rate. Given the organ preservation properties of radiotherapy-only and the better PSS scores, the jury is still out on the optimal treatment for BOT tumors.